essay about covid 19 health protocols

Preparing for the next pandemic: Early lessons from COVID-19

Subscribe to the economic studies bulletin, dante disparte dante disparte chief strategy officer and head of global policy - circle, executive vice president, policy and social impact - diem association, member - fema national advisory council @ddisparte.

February 16, 2021

• 15 min read

COVID-19 has caused more than 109 million confirmed cases , claimed more than 2.4 million lives, and even brought prosperous nations and well-run healthcare systems to their knees. Few countries have been spared. Even in the economically powerful U.S., the tension between maintaining social freedoms and engaging in efforts of collective defense against the virus has led to politicization (e.g., mask wearing, social distancing and vaccine refusal). Sadly, the U.S. is bearing the heaviest human toll from the virus with 25.4 percent of total confirmed cases and more than 486,000 deaths. Fortunately, even in our darkest hour in the fight against COVID-19 – amid a predictable winter surge – there is a light at the end of the tunnel. Pfizer and Moderna have each produced vaccine breakthroughs with 90 percent or greater efficacy, while Johnson & Johnson seeks approval of a single dose vaccine that may be available over the summer. With over 70 million doses delivered across the country, close to 53 million doses have been administered of which 14 million people have received their second shot, breaking the logistical and supply chain log jam that plagued early vaccine efforts.

Even though pandemic preparedness and biodefense have had ardent and clarion supporters, namely Bill Gates and the first Secretary for Homeland Security Tom Ridge , COVID-19 proved how ill-prepared we were to combat a 100-year pandemic. It is not too early to draw lessons from this lack of preparation and global coordination. Not only will doing so aid current recovery efforts, but it would also increase readiness for the next communicable or vector-borne disease to threaten the world. Below are seven areas of opportunity to learn from our COVID-19 response and improve readiness for future pandemic shocks.

Restore institutional trust

Public health always depends on public trust. This is especially true during a global health emergency in which the first line of defense is public adherence to health directives, including to quarantine, observe social distancing, wear masks, and, eventually, receive a vaccine. It is notable that during the 21st century’s pandemics, the most effective remedies borrow from a playbook that is hundreds of years old. Unfortunately, the fight against COVID-19, like past outbreaks and pandemics, has suffered from various perverse, insidious, and conspiratorial setbacks, including the specter of cyber-attacks attempting to thwart the lucrative and geopolitically prized race for a cure or vaccine. Indeed, cyber ne’er-do-wells are also targeting cold supply chains as the mobilization of vaccines gets underway.

The eroding public trust in the Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), World Health Organization (WHO), and pharmaceutical companies more generally has already signaled the need for reform. In the U.S., the CEOs of major pharmaceutical firms , along with industry bodies, have made public pledges that their race for a cure will not succumb to political pressure nor will their companies cut corners on public safety and scientific soundness. Seeing a tension between public interest, shareholder value, and corporate reputation, the private pharmaceutical industry seems to have distanced itself from political interference and emphasized science in their decision making. The same temperament should hold true among political leaders who, in a crisis, must model the behavior they want to see in the public. Such leaders must also provide clear, fact-based information, even if— especially if—it is politically inconvenient.

Fortify early alert frameworks

Some countries, such as Singapore and South Korea , have a comparatively more effective disease outbreak early alert system. This is especially true in Southeast Asia, where people are accustomed to the perennial threat of communicable upper respiratory diseases. Many of these diseases have been identified and mitigated through preventative measures including airport and port of entry screening, temperature checks, and broader social acceptance of wearing masks. Partly due to such measures, countries with crowded urban environments such as Taiwan or Singapore have fared comparatively well in terms of COVID-19 infections even though social distancing (of six feet or greater) may be impossible in some settings such as public transport. These examples demonstrate that building a system for defense against infectious diseases, especially novel or emerging threats, requires an outermost perimeter that serves as a veritable early alert system. Central components of this early alert system include forward-deployed infectious disease specialists, as well as trusted relationships among scientists and epidemiologists. These specialists know the tell-tale signs that a novel virus is emerging and when to sound the alarm – in short, science and data should guide decision-making in response to potential outbreaks.

Sadly, in the case of COVID-19, many components of such early alert systems have been greatly strained, defunded, and politicized, both at the national and global levels. However, in the fight against a so-called “invisible threat,” global solidarity, trust, and real-time threat information sharing are a part of our collective defense. The U.S. is best positioned to lead and refortify these early alert frameworks, beginning with shoring up trust in public health authorities within the country and resourcing them adequately for the global fight against vector-borne and emerging infectious diseases. It was always a matter of time before a new pandemic would occur, and efforts to improve defenses post-COVID-19 should treat the prospect of communicable disease outbreaks like a mathematical certainty.

Threat-based resource allocation

One of the risk management conundrums in pandemic preparedness and biodefense is that the risk feels intangible. Additionally, experts who warn about the specter of contagion are frequently dismissed. Prominent voices from Bill Gates, who sounded a clear alarm at the 2017 Munich Security Conference , to Governor Tom Ridge and Senator Joe Lieberman, who co-chair the bipartisan commission on U.S. biodefense and pandemic preparedness , have largely gone unheeded. COVID-19 must serve as a global wake up call, lest the great human and economic sacrifices are in vain.

Hopefully, the aftermath of COVID-19—which may still be some ways off as the U.S. grapples with a growing third wave and the appearance of mutating variations , which may blunt the effectiveness of vaccines—will recalibrate resource allocation to match the global threat environment. Even in the lead up to the COVID-19 pandemic, U.S. resource allocation for combating infectious diseases and developing biodefense was woefully inadequate. In 2014, the U.S. allocated $6 billion in Federal funding to civilian biodefense, mostly in a diffused manner across a range of research and development programs. Similarly, despite the threat of novel infectious diseases making the “magic leap” and the ever-present specter of bioterrorism or lab-borne threats from malicious actors, this low defensive posture is largely the same around the world.

Comparatively speaking, as a share of global defense spending, the security industrial complex does not allocate nearly enough threat-based resources to mitigating pandemic risk, in the form of money, attention, or human capital. In aviation risk management, there is a process of capturing near misses. By this measure, when it comes to emerging zoonotic risks, scientists have identified 200 zoonoses and seen six registered as a Public Health Emergency of International Concern under the WHO’s emergency classification. Of these, three have been coronaviruses, suggesting that it was only a matter of time before one reached pandemic proportions. Considering the amount of money spent in shoring up the U.S. economy and providing direct relief to citizens (more than $5.7 trillion in economic interventions thus far), pre-investing in infectious disease prevention and meaningful ways of breaking the chain of transmission are clearly a better investment than ex-post efforts to deal with a novel zoonotic health crisis.

Science in the war room

There is an adage in management circles that if you do not measure something, you cannot manage it. In fighting the spread of COVID-19, data and science should be the most critical elements of decision making. Unfortunately, the void of reliable real-time information has been a global challenge during the COVID-19 crisis. This has been particularly true in the U.S., where different states have each pursued varying degrees of transparency, accuracy, accountability, and, critically, methodologies, with regards to reporting infection and casualty rates. In some instances, low-levels of technological processes like the limits of Excel spreadsheets or the specter of keystroke errors, have created misreporting and miscalculation on the number of confirmed cases, as well as the prevalence of community spread.

Another major challenge in the race for a vaccine has been the early, often erroneous signals surrounding the effectiveness of treatments and experimental drugs or vaccines. The world has embarked on nothing short of a vaccine space race to find an effective cure for COVID-19, with some countries, such as Russia, claiming victory early on even though clinical trials have been either scant or could not support efficacy and safety with data. Sadly, even in the face of a global threat, the tendency of economic nationalism and retrenchment stands in the way of global collaboration and solidarity in the race for a vaccine and its global availability. This is true for the vital task of building the type of integrated supply chains that are needed for the provision of lifesaving N95 masks and medical equipment, as well as the high-functioning cold supply chains required to distribute vaccines at global scale. Unless there is great coordination on cold supply chain management, likely led by the logistics prowess of the U.S., the advent of a vaccine may be a Hail Mary pass for many countries wherein poor countries that comprise the largest share of the world’s population may pay the heaviest price of vaccine nationalism.

Privacy preserving technology

Although we have many technological tools that could help control a public health crisis, those tools are only beneficial if the technologies are both trusted and readily deployable. The general lack of reliable, real-time threat information sharing, contact tracing, and community prevalence data during this pandemic has meant people and public health authorities have either been flying blind in the fight against COVID-19 or are relying on backward-looking reporting of confirmed cases. This type of reporting has been particularly plagued with issues: persistent testing bottlenecks, false positive tests, the asymptomatic nature of many cases, and lags in reporting testing outcomes have all presented challenges in mounting an effective and trusted response. The gap in population-scale technologies to facilitate open information sharing, including self-reporting COVID-19 symptoms in a privacy preserving way, is a clear national and global vulnerability. The lack of ubiquitous, trusted technologies in the hands of U.S. citizens confounded real-time risk-reward decision making at the household level.

Playing whack-a-mole with the moving target of a COVID-19 resurgence (including the specter of rapidly evolving variants) without a reliable national COVID-19 dashboard has hampered containment, mitigation, and public health information sharing. In the absence of reliable, real-time data on community prevalence of COVID-19, the assumption is that everyone is a potential threat, which is what makes the “nuclear” lockdown option necessary despite its economically detrimental effects, especially on the most vulnerable people and sectors. Herein lies the difference between risk and uncertainty: risk is measurable, uncertainty is not, which is why the latter is a driver of panic, paralysis, and fear. These are the very conditions that have gripped many parts of the country, as U.S. households have contended with the type of life-or-death decision making usually reserved for battlefields or hospitals.

Indeed, as vaccines are gradually approved, notwithstanding the deleterious effects of vaccine nationalism , containing COVID-19 will require the largest vaccination campaign in U.S. history. As with yellow fever vaccination cards required at ports of entry in a number of countries , the prospect of health passports being upgraded from risk-prone analog cards, which may be lost or forged, is another opportunity to leverage technology. Here, too, the advent of privacy preserving technology in the form of portable e-health passports can provide individual protections and community health assurances as we overcome our trepidations to return to normal. Five major airlines are adopting their own e-health passport as a potential precondition for boarding, along with rapid testing to augment potentially porous airport screening or traveler-provided assurances on pre-travel health. Until population-scale clearances are provided, restoring trust and business as usual may see two populations being served: one group that can provide high-assurance on COVID-19 immunity may be allowed to resume a semblance of normal activities, while the other may struggle with restrictions until the chain of transmission is broken.

Mass casualty surge capacity

There is a fundamental tension between public health emergencies—and their resulting need for collective defense against a pandemic—and privatized healthcare. The definition of a moral hazard is risk-taking behavior without bearing the consequences of the risk. The vulnerability of an unequal and ill-prepared U.S. public health system, where more than 26 million people are functionally out of the system (as uninsured or poorly covered), has been laid bare during the COVID-19 pandemic. Not only did the material scarcity of life-saving equipment like ventilators and personal protective equipment (PPE) – among other essential supplies – imperil frontline healthcare workers, but it also often consigned those with treatable conditions to their death.

There is a clear need for improved universally accessible emergency healthcare surge capacity to respond to mass casualty events. The national healthcare emergency perimeter should reach 100 percent of the U.S. population, particularly when combating the spread of an infectious disease or responding to a wide-scale bio-hazard event or other mass casualty threat. The medical and emergency management professionals on the frontlines, meanwhile, should never experience a shortfall of predictably necessary and life-saving supplies. Sending healthcare professionals to fight COVID-19 with ill-fitting, reused, or patchwork PPE, is tantamount to sending soldiers into battle without body armor or weapons. In keeping with this combat analogy, the nation’s healthcare and emergency response system must also draw lessons learned from the COVID-19 response and formulate tabletop exercises and preparedness drills that treat mass casualty events, communicable diseases, and bio-threats as ever present, rather than as so-called black swans or statistically rare events.

Public-private accelerator

If and when the world sounds the all clear on COVID-19 and the global economy returns to a new normal, a generational debt of gratitude will be owed to scientists and medical professionals. The pandemic, like prior global crises, has blurred the lines between public and private resources. In many countries, including the U.S., governmental powers usually reserved for times of war were used to compel the private sector’s balance sheet to make a down payment on the greater good. While some firms responded to this call to action affirmatively and on their own volition, others will be compelled by the Defense Production Act , not realizing that shielding their balance sheet amid total economic collapse would be a reputation tarnishing Pyrrhic victory. This is especially true considering the scale of the taxpayer backstop that has been deployed in the U.S. in an unprecedented mobilization of the government’s financial wherewithal to stave off massive layoffs, business closures, and economic ruin.

In all, the economic response to COVID-19 has tipped already perilous U.S. debt-to-GDP rates to stratospheric heights not seen since World War II. With national debt projected to be greater than the size of the U.S. economy, the down payment on COVID-19 response and recovery will require generational commitments to ensure national resilience in the face of future threats. A public-private approach to catalyzing national and global resilience to large-scale emerging threats such as climate change , pandemic preparedness, and biodefense, among others, would be a more effective use of resources than addressing a catastrophic event without a plan. Operation Warp Speed, the nom de guerre for the U.S. race for a cure, has mobilized what is ostensibly the fastest pursuit of a safe vaccine in history and has also shown the benefits of purposeful societal collaboration. The U.S. is not alone in this quest. If this type of innovation accelerator were not a zero-sum proposition for each country but rather a globally shared and pre-funded capability immune from corporate intellectual property restrictions and national interests, the potential for broad societal benefits would be unprecedented.

The dreadful human, economic and sociopolitical toll of the COVID-19 pandemic hearkens to a war time effort. Rather than combating this disease in global solidarity, many countries and regions have opted to go it alone, ignoring the reality that against a threat unseen like a novel zoonotic disease, porous national borders that depend on the arteries of trade, integration, and globalization, will offer little defense. Some of the capabilities established in response to COVID-19 should remain in place, including and especially reinforced early alert frameworks that can serve as a proverbial tripwire that a novel virus, vector-borne disease or other bio threat has surfaced. These early alert systems are a global tripwire framework that all countries must contribute to and believe in. Similarly, once the tendencies of vaccine and resource nationalism are overcome, countries must realize that in the face of pandemic and other global threats, we are in effect as strong as the weakest link. U.S. leadership in strengthening the chain of pandemic resilience will be a vital catalyst to ensuring the world is prepared for the next one and that the costly lessons from COVID-19 prepare future generations.

Science coupled with focused public spending or guaranteed demand for billions of vaccines has produced multiple breakthroughs in record time compared to the typical 12 to 18 months it takes to develop a new vaccine. This rapid vaccine development capability should not be disbanded once COVID-19 is contained, especially as many developing countries will rely on coordinated international assistance to contain domestic outbreaks and prevent mutations from leaping over national borders. COVID-19 bears many similarities to other global threats, such as climate change, severe income inequality and societal polarization. Like COVID-19, responding to these threats will require a societal approach, tradeoffs across the public and private lines and trusted public leadership that people will follow.

Dante Alighieri Disparte is Founder and Chairman of Risk Cooperative, a risk management and insurance advisory firm; a member of FEMA’s National Advisory Council; a member of the World Economic Forum Digital Currency Governance Consortium; and Executive Vice President of the Diem Association. The author did not receive financial support from any firm or person for this article or, other than the aforementioned, from any firm or person with a financial or political interest in this article. Other than the aforementioned, he is currently not an officer, director, or board member of any organization with an interest in this article.

Economic Studies

Center on Regulation and Markets

Andrew Atkeson, Stephen Kissler

March 27, 2024

Anna Saavedra, Morgan Polikoff, Dan Silver

March 26, 2024

Vanda Felbab-Brown

March 21, 2024

• Research article
• Open access
• Published: 03 December 2020

Comparative analysis of COVID-19 guidelines from six countries: a qualitative study on the US, China, South Korea, the UK, Brazil, and Haiti

• Ji Youn Yoo 1   na1 ,
• Samia Valeria Ozorio Dutra 2   na1 ,
• Dany Fanfan 3 ,
• Sarah Sniffen 4 ,
• Hao Wang 5 ,
• Jamile Siddiqui 6 ,
• Hyo-Suk Song 7 ,
• Sung Hwan Bang 8 ,
• Dong Eun Kim 9 ,
• Shihoon Kim 10 &
• Maureen Groer 1  

BMC Public Health volume  20 , Article number:  1853 ( 2020 ) Cite this article

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In late January, a worldwide crisis known as COVID-19 was declared a Public Health Emergency of International Concern by the WHO. Within only a few weeks, the outbreak took on pandemic proportions, affecting over 100 countries. It was a significant issue to prevent and control COVID-19 on both national and global scales due to the dramatic increase in confirmed cases worldwide. Government guidelines provide a fundamental resource for communities, as they guide citizens on how to protect themselves against COVID-19, however, they also provide critical guidance for policy makers and healthcare professionals on how to take action to decrease the spread of COVID-19. We aimed to identify the differences and similarities between six different countries’ (US, China, South Korea, UK, Brazil and Haiti) government-provided community and healthcare system guidelines, and to explore the relationship between guideline issue dates and the prevalence/incidence of COVID-19 cases.

To make these comparisons, this exploratory qualitative study used document analysis of government guidelines issued to the general public and to healthcare professionals. Documents were purposively sampled ( N  = 55) and analyzed using content analysis.

The major differences in the evaluation and testing criteria in the guidelines across the six countries centered around the priority of testing for COVID-19 in the general population, which was strongly dependent on each country’s healthcare capacity. However, the most similar guidelines pertained to the clinical signs and symptoms of COVID-19, and methods to prevent its contraction.

In the initial stages of the outbreak, certain strategies were universally employed to control the deadly virus’s spread, including quarantining the sick, contact tracing, and social distancing. However, each country dealt with differing healthcare capacities, risks, threats, political and socioeconomic challenges, and distinct healthcare systems and infrastructure. Acknowledging these differences highlights the importance of examining the various countries’ response to the COVID-19 pandemic with a nuanced view, as each of these factors shaped the government guidelines distributed to each country’s communities and healthcare systems.

Peer Review reports

Introduction

The recent outbreak of COVID-19 has led to a major concern of increased mortality in the world. The first outbreak of COVID-19 was reported in Wuhan city, the capital of China’s Hubei Province, in late December, 2019 [ 1 ]. Only a few months later, on March 11, 2020, the World Health Organization (WHO) designated the COVID-19 outbreak a pandemic and provided guidelines for COVID-19 case management in the health facility and community. Globally, approximately 3,506,577 confirmed cases of COVID-19 have been reported, including over 247,467 deaths (Johns Hopkins University, May 03, 2020) [ 2 , 3 ]. The fast spread of the virus reflects how health is connected globally and the necessity of investing in global research efforts to explore, clarify, and address global health emergencies.

When the first COVID-19 outbreak was reported in China, the Chinese government established guidelines that recommended keeping social distance in public places, staying at home, and isolating infected populations to contain the epidemic. After a month, South Korea was assailed by a COVID-19 outbreak. Both governments’ early actions were aggressive in an attempt to stop the virus from spreading, involving both widespread testing for the virus and contact tracing. The COVID-19 response in China and South Korea provided the model for other countries where COVID-19 was just beginning to expand. While it was uncertain whether other countries could implement or adapt the stringent measures endorsed by China and South Korea, the heterogeneous nature of the virus worldwide warranted further investigation into the healthcare and community responses from governments across many nations.

Considering how each country had different capacities, risks, threats, political and socioeconomic challenges, as well as different health care systems, it was unsurprising that each country responded to this threat with different measures and different timings. However, it is also clearly critically important to look at how different countries addressed the first pandemic of coronavirus. Thus, we compared six different countries’ guidelines to investigate their management, incidence, and prevalence of COVID-19 cases. Additionally, we explored the relationship between the guidelines’ issue dates and the prevalence-incidence curves of the different countries.

The objective was to compare government guidelines on COVID-19 by six different countries (The United States (US), China, South Korea, The United Kingdom (UK), Brazil and Haiti). This included general public guidelines and healthcare professionals’ (medical institutions) guidelines. We aimed to identify differences and similarities between the countries’ community and healthcare professional guidelines and additionally to explore the relationship between guidelines issue dates and the prevalence/incidence of the COVID-19 cases. This is significant because we can examine how various countries responded to COVID-19 and identify best practices. This approach also allows us to understand how healthcare system and policy capacities shape COVID-19 responses and to share this information to improve responses to COVID-19.

Research design

Our study used document analysis, a standard qualitative research method for evaluating communication and policy research, to explore the differences and similarities between government COVID-19 guidelines from six countries [ 4 , 5 ]. The following steps were included in the analysis: (i) establishing the document inclusion criteria, (ii) gathering documents, (iii) analyzing key areas, (iv) coding the document, (v) verification, and (vi) analysis [ 6 ]. In this approach, the investigators are the primary means of data selection and analysis. This study used purposive sampling to recruit investigators internationally by email and/or phone.

Country selection

COVID-19 is a global pandemic warranting a cross-national perspective from countries differing on several levels (e.g., geographic region, health and economic resources, stage of COVID-19 spread and response) to maximize range and diversity when exploring the scope of COVID-19-related community and healthcare system guidelines. When selecting the six countries, the following were considered: 1) COVID-19 starting and spiking period, 2) geographic proximity to China, where the COVID-19 spread began, 3) population size, 4) gross domestic product (GDP) status, and 5) eligibility of a bilingual expert in the public health field. For instance, the first COVID-19 outbreak occurred in China in December 2019. Outbreaks in other countries like South Korea, the US, and the UK soon followed in January and February 2020. Finally, in March 2020, Brazil and Haiti noted increased incidence and deaths from the virus. By April 2020, China and South Korea were in the recovery stage of the pandemic while the spread of COVID-19 intensified in countries such as the US, UK, Haiti and Brazil. Geographical differences in the selected countries reflected geographic proximity to China (Korea), largest population in North America (the US), largest population in South America (Brazil), and island countries with significant geographic distance from China (Haiti and the UK). Furthermore, the countries’ population sizes were strongly related to the effectiveness and widespread dissemination of information regarding COVID-19 guidelines [ 6 ]. Additionally, the countries’ GDP represented their resources, ability, and strategies employed in response to COVID-19. For instance, at the start of the COVID-19 spread in the UK and Haiti, both countries had very little available resources for COVID testing. With Haiti’s fragile health care system, Haiti did not have the infrastructure to fight the spread of the virus, warranting economic support from other countries. Finally, it was necessary to collaborate with authors who met the following inclusion criteria in order to facilitate document analysis of different countries’ government guidelines: hold a graduate degree, have experience with healthcare material, are fluent in English and have native language fluency (Chinese, Korean, Portuguese, and French/ Haitian Creole) in at least one of the six countries selected.

Document inclusion/exclusion criteria

Six members of the research team, which consisted of multidisciplinary, cross-cultural researchers, collected the data. The research team only reviewed documents from publicly available government websites for each country (see Additional file  1 ). Guidelines from government websites were available in different formats, including action and response plans, healthcare and general population guidelines, prevention measures/recommendation flyers, videos, government memos and webpages. Documents or information from nongovernment websites, social media, online newspapers/editorials, peer-reviewed articles, and heath institution guidelines were excluded from the study.

Data collection

To guide document selection among investigators, a codebook was developed which highlighted the information necessary for each theme (see Additional files  2 and 3 ). Each document for each country was reviewed to determine the extent to which the document provided answers to at least one of the pre-identified themes (i.e. areas of analysis). The team reviewed government websites weekly for approximately 6 weeks from March 2020–May 2020 to obtain information from government guidelines, and to ascertain whether any new documents were published, or whether old guidelines had been updated. A total of 55 documents (e.g., government guidelines, flyers, memo, webpages) were reviewed to extract data (10 for the US, 3 for China, 10 for South Korea, 8 for the UK, 13 for Brazil, 11 for Haiti) (see Additional file  1 ). Texts from COVID-19 general public guidelines and government health promotion materials relevant to each pre-identified theme were copied verbatim in their original language and added to an excel spreadsheet. Extracted verbatim texts written in a language other than English (Portuguese, Chinese, Korean, and Haitian Creole/French) were translated to English by bilingual members of the research team and added to the excel spreadsheet to allow for review and analysis of the information as a group (see Additional file  3 ). Text translation focused primarily on maintaining meaning consistent with health care language rather than cultural nuances, thus, formal translation procedures (e.g., forward and back translation) were not completed. The authors evaluated the English translations, providing constructive feedback about the translation, and confirmed their validity through governmental and professional guidelines and articles.

Data analysis

Key areas of analysis were articulated in the codebook, which provided a list of codes (e.g., themes and sub-themes) and included six basic components: the code, a brief definition, a full definition, guidelines for when to use or not use the code, and examples of the code. Explicitly, the codebook helped the research team determine the meanings of themes and provided clarity about what to look for within the text of the guidelines. The codes’ sensitivity and specificity were used as a tool for measuring the adequacy of answers to research questions. Data analysis entailed appraising and synthesizing texts from guidelines, which were then organized into major themes and sub-categories through content analysis [ 7 ]. Content analysis within the research team was facilitated through online meetings, which were convenient and removed geographic barriers. Researchers assessed the data for coding patterns (e.g., similarity, differences, frequency) across different countries regarding their government guidelines for the general public and healthcare professionals. All texts from guidelines were allocated deductively to the a priori themes (deductive codes). During the iterative content analysis process, new themes also emerged (inductive codes). When disagreement ensued during data analysis, the research team recoded, or the primary coder sought advice from another team member for verification and clarification [ 7 ]. The original data of the confirmed and deaths cases were downloaded from the Johns Hopkins University Center for Systems Science and Engineering [ 3 ]. Tableau, a well-known website for analyzing big data, was used to clean and reshape the data for sharing with the public. The data was then converted to excel files and used to create figures (see Additional file  4 ) [ 8 ].

Trustworthiness of the data

We established trustworthiness of the data by: 1) focusing on government guidelines, as they are a credible source of information (credibility), 2) using information from guidelines, which maintain dependable and consistent patterns over time and are periodically updated to reflect the evolving understanding of the coronavirus (dependability), 3) using government guidelines, which limited the research team’s bias at the data collection and interpretation level, and improved accuracy with the use of a well-developed codebook ( confirmability), and 4) analyzing the guidelines of six countries experiencing the coronavirus pandemic at the same time but within different contextual realities (transferability) [ 9 , 10 ].

Theme: Evaluation and testing

Sub-them: screening criteria.

When comparing the different government guidelines on screening for signs and symptoms in suspected COVID-19 cases, all countries listed respiratory symptoms as a criterion and the majority – Brazil being the exception – emphasized fever, as well. Interestingly, the US and UK did not list travel history as a criterion. We also noticed that the US and Brazil did not categorize pneumonia as a screening criterion, whereas South Korea, the UK and Haiti emphasized unknown case of pneumonia, clinical or radiological evidence of pneumonia, and bronchopneumonia. A major distinction the authors noted was that only China and the UK specified the detection of suspected COVID-19 cases within the hospital through either radiological evidence via chest X-ray and thoracic Computed Tomography (CT) or lymphocyte counts. Haiti, as of April 20, 2020, expanded the screening criterion from ‘have a fever greater than 38°C within the last 10 days’ to ‘anyone with fever greater than or equal to 38 °C (see Additional file  3 ).’ Haiti’s screening criteria also included body aches, sudden changes in taste (ageusia) or smell (anosmia), possibility of coming in contact with a healthcare professional diagnosed with COVID-19, or being an occupant of a high risk area while experiencing symptoms compatible with COVID-19 (see Table  1 ).

Although information about contact with suspected and/or confirmed cases was vital for screening criterion in most countries, the US and UK did not include this. Furthermore, specifically examining symptomatic patients aged over 65 or who had underlying conditions was only found in the US guidelines (see Table  1 ). Of note, South Korea created a new category in addition to the suspected cases called the Patient Under Investigation (PUI) on April 03, 2020. A PUI is a person who has an epidemiologic link to a collective outbreak of COVID-19 in an area, or a possible contact to a COVID-19 positive person. The US used the term PUI to describe people who exhibit symptoms, or were otherwise suspected of having COVID-19, but had not yet been confirmed via laboratory testing.

Sub-theme: Screening center types

Across different countries, we identified three different types of screening centers: healthcare facilities, drive-through screening clinics, and walk-through screening clinics. While walk-through screening clinics were available in South Korea, healthcare facilities were the only screening centers available in Brazil and Haiti. Interestingly, Brazil and China did create other satellite facilities for treatment, even though they did not create separate facilities for screening. The US, UK and South Korea conducted drive-through screening clinics.

In particular, South Korea took a distinctly different approach to managing suspected COVID-19 cases. Patients with respiratory symptoms that fit the COVID-19 suspected case criteria were blocked from entering the designated healthcare facilities (called the Public Relief Hospital System) and were redirected to other COVID-19 screening/test centers, or if the hospital was a screening center itself, the patient suspected of having COVID-19 was directed to use a specific entrance for COVID-19 screening before entering the main hospital building. The purpose of establishing the Public Relief Hospital System was to provide safe hospital environments protected against COVID-19 spread. In other words, this was an attempt to block patients with COVID-19 from spreading the virus to general patients who did not have COVID-19.

Theme: Infection control

Sub-theme: general outpatient guidance.

Outpatients are patients outside of the hospital who need periodical medical attention due to other morbidities (hypertension, cancer, HIV/AIDS, etc.). In South Korea, outpatients who require healthcare service due to non-COVID-19 diseases were directed to the Public Relief Hospital for follow-up or to see a doctor. These outpatients were strictly separated from patients with any respiratory symptoms.

In Brazil and the US, outpatients were advised to call ahead of their appointment time and were asked whether they had experienced symptoms of respiratory infection. The UK and Haiti avoided treating outpatients in their healthcare facilities. Still, the UK continued with outpatient appointments either through video or phone clinics. Chinese patients, on the other hand, could make an appointment via the phone or online and could then complete their appointment in the hospital as long as the patient made the appointment with a specialist and avoided using the emergency room (ER) or fever clinics where COVID-19 patients had been treated. Haiti did not provide recommendations regarding whether outpatients should make appointments with clinics, and outpatient services were unavailable to the general population. However, Haiti did provide some guidance for those with HIV/AIDS, as Haiti has a high number of individuals suffering from HIV/AIDS. The US updated their guidelines in April 13, 2020, advising healthcare facilities to implement alternatives to face-to-face triage and visits, and instructing patients to utilize cloth face coverings regardless of symptoms upon entry to a healthcare facility. However, the guideline did not specify what alternatives were implemented.

Theme: Cost support

Sub-theme: cost support.

Financial support for testing and treatment was provided mainly or totally by the government in South Korea, the UK, and Brazil. In Haiti, the Haitian government, the US, and the World Bank’s Board of Executive Directors, in conjunction with several international and private organizations, donated money to cover the cost of the country’s COVID-19 response. In China, an individual’s medical cost was subsidized based on the subsidy policy of the local area if the patient was suspected of having COVID-19. However, once the patient received confirmation of COVID-19 infection, the medical cost was subsidized by the authorities. The cost of the clinic visit and testing was made free for all US citizens regardless of insurance status, per The Families First Coronavirus Response Act, which required private and federal insurance to pay for Food and Drug Administration (FDA)-approved testing, and for testing to be free to those who were uninsured. The extent to which the COVID-19 treatment was covered differed between insurance companies.

Sub-theme: Confirmation of COVID-19

All six countries performed real time PCR to confirm COVID-19 cases. Uniquely, the UK did not provide testing for COVID-19 to the community (at the time of writing), and instead reserved testing for National Health Service (NHS) staff, their relatives and – later in the pandemic – select essential workers. Some unique types of confirmatory lab tests were via virus isolation in South Korea, virus gene sequencing in China, and serological examination in Brazil, Haiti, and the US.

Brazil made the decision to include epidemiological criteria, meaning a confirmed case could be included if the individual met clinical criteria and epidemiological evidence, despite a lack of confirmatory laboratory testing for COVID-19. The US, however, made the distinction that an individual who met those guidelines was considered a probable case. The US also described probable cases as a person meeting the presumptive laboratory evidence and either the clinical criteria or the epidemiological evidence. Finally, an individual could be considered a probable case by the US if their vital records, as in their death certificate, indicated the person died of causes related to COVID-19, despite not having a confirmed laboratory test result.

Theme: Triage protocols

Sub-theme: hospital admission criteria.

All countries’ hospitalization decisions were made on a case-by-case basis. While Haiti’s hospitalization criteria were not specified by the government, Brazil relied on post-collection medical evaluation for hospitalization decisions. The Chinese guideline did not indicate hospital admission criteria. The US recommended hospitalization of people with severe symptoms: septic shock, sepsis, pneumonia, hypoxemic respiratory failure, acute respiratory distress syndrome (ARDS), and cardiomyopathy, etc. The UK required either clinical evidence of pneumonia or radiological evidence with a high suspicion for COVID-19, with ARDS-like or influenza-like symptoms for hospitalization.

Uniquely, South Korea created three different categories, ranging from moderate, severe, to extremely severe for hospitalization. Asymptomatic COVID-19 positive individuals or those with mild symptoms were sent to the Living Treatment Center, a facility that monitored symptoms twice a day and transferred support to the hospital in the event of a worsening of symptom severity.

Sub-theme: Healthcare triage isolation

All six countries developed an isolated area for screening and follow up for symptomatic patients in order to isolate suspected cases. Brazil and the US advised healthcare facilities to place suspected cases in well ventilated spaces that allowed sufficient space between patients. South Korea, Haiti, and China organized their healthcare facilities into different levels of care according to the absence or presence of respiratory symptoms. More specifically, China categorized triage isolation areas into those for confirmed, suspected, or non-COVID-19 patients.

Sub-theme: Visitor access to healthcare facilities

In China, visitors were prohibited from accessing healthcare facilities, whereas the UK and South Korea made exemptions for seriously ill patients receiving end-of-life care, who were allowed one visitor per ward patient. Brazil and Haiti limited the number of visitors to the minimum amount possible, but only Haiti required that all visitors entering the hospital wear a face mask. Although earlier in the pandemic the US made no recommendations regarding visitor access, by April the US Center for Disease Control and Prevention (CDC) advised hospitals to limit the number of visitors allowed.

Except for China’s guidelines, all countries took extra precautions towards visitors, establishing protocols for visitors regarding proper Personal Protective Equipment (PPE) and hygiene. Although the US CDC guidelines were not as restrictive as other countries regarding visitor limitations, the US guidelines suggested actively screening visitors for fever and COVID-19 symptoms upon entry to healthcare facilities. If COVID-19 symptoms were present, the guidelines advised that the visitor not be allowed entry to the facility. Similarly, Brazil suggested avoiding entry of visitors with respiratory symptoms. The US CDC and the Brazilian government also recommended posting visual alerts advising visitors to wash their hands frequently, limiting visitors to the most vulnerable patients (i.e. oncology and transplant awards), encouraging the use of videocall applications in place of in-person visits, and recommending visitors leave the patient during aerosol generating procedures or other specimen collection procedures. Lastly, Brazil and the US instructed visitors to only visit the patient’s room, not any other locations in the facility.

Community guidelines

Theme: prevent getting sick, sub themes: prevent getting sick.

Most recommendations to the community on preventing getting sick were similar between the six different countries. In order to explore the major differences, the sub-themes were organized according to singular actions (i.e. total time washing hands, covering cough and sneezes, face-cover recommendations, etc.).

Generally, face-cover recommendations changed throughout the pandemic, however South Korea and China recommended the use of face masks in public places from the beginning of the pandemic, even if the individual was not sick. The UK did not indicate clear guidance on this matter. The US, Brazil, and Haiti did not initially recommend wearing a face covering, however, the guidelines were updated by the US CDC on April 4th, 2020, by the Brazilian Health Ministry on April 5th, 2020, and by Haiti in the middle of April 2020 to indicate that all people, regardless of whether they were sick, should wear a cloth face covering in public. However, medical grade face masks were still not recommended for the community, as they were to be reserved for health care workers due to shortages.

South Korea, Brazil, Haiti, the US and the UK did not provide guidance on the sharing of personal items in the general community guidelines regarding the prevention of getting sick. China was the only country who mentioned not sharing any personal items to the community as a method for preventing contraction of COVID-19.

Even though most community guidelines on preventing illness recommended maintaining 1.8–2.0 m of physical distance between people to avoid viral transmission, Haiti’s guidance on physical distancing initially recommended staying two steps away from other individuals. Haiti updated their recommendation to staying three steps away from others on April 20th.

As of April 8th, 2020, as a unique measure to prevent viral spread, the South Korean government made it mandatory for all Koreans and long-term stay foreigners who entered South Korea to (1) be tested for COVID-19, (2) install an application on their cell phones: the Self-quarantine Safety Protection App, and (3) abide by the guidelines for self-quarantined persons, including conducting self-diagnosis for a period of 14 days (see Table  2 ).

Theme: If you are sick

Sub theme: what to do if you are sick.

Based on the guidelines, we were able to extract 8 important terms, including avoid using public transport and crowded places, isolation days and next steps, face mask or cloth face covering, use a separate room or bathroom, sharing household items, sick room ventilation, cleaning instructions, call center for COVID-19 (see Table  3 ) . These terms were ascertained from at least two countries’ guidelines.

Five of the countries recommended people with respiratory symptoms stay at home for certain periods, whereas the Chinese guidelines advised sick people to immediately go to a designated medical care institution for testing, and to then follow the quarantine protocols requested. Each country designated different isolation periods and procedures. As reported by the US and the UK governments, people with respiratory symptoms were to isolate at home and only stop home isolation under the following conditions; no fever for at least 72 h without the use of medications that reduced fever, improvement of other symptoms, and the passage of at least 7 days since symptom onset. Brazil and China advised that, in addition to the person with respiratory symptoms, all family members or fellow residents were to be quarantined for 14 days. In South Korea, any person who had COVID-19 symptoms was mandated to stay at home for at least 3 to 4 days and was then called and given advice by the Korea Centers for Disease Control and Prevention (KCDC) call center.

To prevent the spread of the virus between family/household members, the US, South Korea, and Brazil recommended the ill person be confined to a separate room and bathroom and avoid sharing personal household items. Haiti, China, and the UK did not provide guidance on providing a separate room/bathroom or on sharing personal items.

Isolation room ventilation, such as keeping the window open for air circulation or closing the door, were mentioned in the South Korean and Brazilian guidelines. Cleaning instructions for containing the virus were indicated in different ways in each country, except for in the UK and Haiti. Call centers for COVID-19 were conducted in South Korea, Haiti, and Brazil in the very early stages of the pandemic.

Sub theme: Threshold to contact a healthcare provider

Across the countries examined, the threshold symptoms for when to contact healthcare providers varied. South Korea advised sick people to contact a healthcare provider if the person had a fever (37.5 °C) or if symptoms worsened. Brazil recommended seeking help if the ill person experienced shortness of breath. The US advised individuals to get medical attention if they experienced persistent pain, chest pressure, cyanosis on lips or face, new confusion, or if unable to be awakened. Haiti mentioned contacting a healthcare provider if the individual had respiratory symptoms. Besides the usual respiratory acute signs (fever, shortness of breath), China also mentioned acute digestive tract symptoms as a reason to reach out to a healthcare facility. In the UK, if a person’s symptoms worsened to the point where they were having difficulty breathing, they were advised to go to the hospital by ambulance facilitated by the online NHS service.

Sub-theme: Transport to healthcare facilities

The US, South Korea, and China recommended using personal vehicles and to avoid using public transportation to reach healthcare facilities, however South Korea and China specified that individuals should cover their face with a face mask before reaching healthcare facilities. Five of the countries allowed ambulance transport, with the exclusion of China.

WHO acknowledged and announced the impact of COVID-19 on both public health and economic sectors via two interim guidelines published in late March 2020. WHO also emphasized the importance of preparedness for the COVID-19 pandemic, accounting for the countries’ health care capacities [ 11 , 12 ]. The six countries tend to align with the WHO interim guideline, however there are some differences in the response to the pandemic in each country.

The major differences in evaluation and testing criteria in the guidelines across the six countries centered around the priority of testing for COVID-19 in the population, which strongly depended upon each country’s healthcare capacity including accessibility to healthcare providers, having enough testing kits and reagents, availability of hospital beds, and so on. The most similar recommendations in the evaluation and testing criteria from each government were those pertaining to the clinical signs and symptoms, such as fever and respiratory symptoms, as the priority criteria to initiate COVID-19 testing.

During the writing of this paper, there were no known vaccine or antiviral therapies for COVID-19. Therefore, early detection and diagnostic testing for SARS-CoV-2 were vital to reducing transmission, managing active cases, contact tracing, and understanding epidemiology [ 13 ]. The government guidelines concerning screening criteria and capacity for screening – including screening centers, and laboratory testing for COVID-19 in suspected or confirmed cases –were crucial factors in protecting the public from the virus. The WHO criticized countries that had not prioritized testing for COVID-19. Tedros Ghebreyesus, the chief executive of WHO, emphasized the importance of testing by stating, “The most effective way to prevent infections and save lives is breaking the chains of transmission. You cannot fight a fire blindfolded, and we cannot stop this pandemic if we don’t know who is infected. We have a simple message for all countries: test, test, test, test” [ 14 ]. However, lack of reagents and/or testing capacity for the SARS-CoV-2 virus challenged all nations included in the study, at least at the beginning of the pandemic. The US, UK, Haiti, and Brazil, in particular, experienced problems with shortages of testing kits for SARS-COV2 due to rapidly increasing demand compounded by national supply chains under stress and national laboratories with limited experience in COVID-19 virus testing [ 15 , 16 ]. This had a negative impact by potentially obstructing the expansion of COVID-19 testing criteria, resulting in a narrowed range of people undergoing COVID-19 testing, which may have led to increases in the actual number of cases and overall risk of death by COVID-19, but falsely decreased the number of confirmed cases and deaths reported in the nations’ statistics.

According to the UK’s NHS, testing priority was given to 1) intensive care unit patients with suspected coronavirus, 2) patients with severe respiratory illness including pneumonia, 3) isolated cluster outbreaks, and 4) random testing for surveillance purposes [ 17 , 18 ]. The first 2 confirmed cases occurred in the UK on January 31, 2020 and the first COVID-19 victims died on March 7, 2020 (see Fig.  1 ). After 20 days, although the UK only tested people who were admitted to hospitals, the number of confirmed cases and disease-related deaths dramatically increased (confirmed cases: 14,745, deaths: 1163) [ 19 ]. By April 7, 2020, 1 month after the first COVID-19 deaths, more than 1000 people were dying every day due to viral infection (see Fig.  1 ). In April 9, 2020, despite the thousands of citizens dying daily due to COVID-19 related causes, the UK government launched large COVID-19 testing centers which prioritized processing samples from health-care workers in self-isolation, allowing them to go back to work [ 18 ]. Therefore, people who were not considered a priority, such as non-health care providers or community members with mild respiratory symptoms, were not given access to testing. The limited scope of the UK’s testing approach for COVID-19 was due to a capacity problem, resultant to the consolidation in the number of pathology laboratories nationwide [ 18 ]. Many laboratories were centralized, which led to the possibility that each hospital would not necessarily be equipped with a fully functioning lab. This systemic capacity problem may have increased the risk of spread by free movement of people who were suspected of having the disease, since testing was unavailable to those individuals to enforce a stay-at-home order. In the UK, 90,000 people were tested as of the 24th of March - around 1300 COVID-19 tests per million people. Although it was a higher portion than some nations, including the US (around 74 per million as of the 16th of March), it was far behind South Korea (5200 per million as of the 17th of March) [ 20 , 21 ].

COVID-19 Cases in six countries

Initially, the US’s CDC included fewer testing criteria than the WHO guidelines. The CDC guidelines recommended testing individuals with a body temperature above 38 °C (fever) and lower respiratory symptoms, those who had a fever and a travel history to China, or those who had a fever and were possibly exposed to a suspected or confirmed COVID-19 case. However, once a patient who did not have any travel history or exposure to any confirmed COVID-19 cases was reported COVID-19 positive, the CDC expanded their testing criterion to include any individuals admitted to a hospital due to lower respiratory symptoms and fever. This addition broadened the spectrum of patients being tested, but also led to rapid increase in the demand for testing.

In February 2020, the CDC acquired, developed, and distributed COVID-19 testing kits to laboratories nationwide, almost one hundred of which reported experiencing several issues with the testing kits. These issues included the failure of negative controls and presentation of inconclusive results. After an internal investigation on February 12, 2020, the CDC reported a faulty reagent as the issue. The CDC immediately recalled all unreliable testing kits and promised to re-manufacture the faulty component and distribute the newly developed reagent to the public health labs as soon as possible. Ultimately, the shortage of COVID-19 test kits at this critical time point possibly interfered with the prevention of increasing confirmed cases early in the outbreak. Furthermore, although the number of confirmed cases and death rate significantly increased each day after March, 20, 2020 in the US (confirmed cases per day around 15,000, deaths per day around 1000), only 97 public health laboratories finished verification and were offering testing on May 6, 2020 [ 22 ]. As further evidence of inadequate testing capability, the CDC announced that “although supplies of tests are increasing, it may still be difficult to find a place to get tested” [ 22 ].

Together, the capacity for widespread testing and presence of prepared health facilities were key to controlling the dissemination of coronavirus, as evidenced by South Korea. The first COVID-19 incident in South Korea was announced on January 31, 2020, with 7 confirmed cases. The daily confirmed cases remained low for the following month (confirmed cases: 100, deaths: 1) until a super spreader event was initiated on February 29, 2020. Each day for 9 days afterward, the country’s epidemic curve resembled a steep staircase as infections climbed, resulting in dramatically increased confirmed cases and deaths (see Fig.  1 ). However, by implementing large-scale governmental COVID-19 testing, health officials were able to effectively contact trace and send potentially infected people into quarantine as a preventative measure. By March 25, 2020, more than 357,000 Koreans had been tested. The country reported 10,804 total coronavirus cases and 254 deaths as of May 1, 2020. This was the lowest death rate among the countries examined [ 3 , 23 ]. Having previously dealt with the Middle East respiratory syndrome (MERS) in 2015, South Korea had already prepared for potential outbreaks of large-scale epidemics, for example by installing negative pressure rooms in hospitals in 2018. Additionally, the country rapidly developed large-scale availability of COVID-19 testing locations, such as K-Walk-Thru and Drive-thru testing stations. These were the first testing centers of their kind in the world and facilitated the quick and safe collection of samples for COVID-19 testing. These unique centers helped not only reduce the risk of cross infections at the in-hospital testing centers, but also increased daily testing capacity amid rapidly rising rates of new cases [ 24 ].

WHO emphasized the prioritization of isolated care for patients with higher risk of infection, such as severe and critical illness patients aged over 60 years, and those with underlying medical conditions [ 25 ]. Still, exponential escalation in the number of daily confirmed cases placed enormous strain on national medical systems, resulting in limited or total lack of beds for COVID-19 treatment. Therefore, the US, UK, South Korea, Brazil, and Haiti decided patients with mild to moderate coronavirus symptoms should be observed in “Home Isolation”. This approach was a crucial option that only required modification in individual behavior without supplementary expenditure.

Interestingly, China opposed observing mild to moderate coronavirus cases at home, instead directing all potentially infected persons to designated medical care institutions. This policy was initiated in Wuhan, the city where COVID-19 emerged in early February 2020 [ 26 ]. On March 27, 2020, more than 60% of coronavirus cases in the country were at Wuhan (see Fig.  1 ). The city converted exhibition centers and stadiums into shelter hospitals within mere weeks. Epidemiological evidence at the beginning of the pandemic revealed high intrafamily transmission, with 75–80% of all clustered infections diagnosed within families [ 26 , 27 ]. Quickly emerging alternative hospitals, such as the Fangcang Shelter Hospitals, dedicated to testing and admitting only COVID-19 patients may have led to a reduction in the spread of the virus in the community, thereby decreasing the number of new cases during the pandemic.

On January 22, 2020, the WHO announced the presence of travel-related cases linked to Wuhan City, human-to-human transmission, and reported COVID-19 had been observed outside of China. The WHO strongly advised individuals to report their travel history to their health care providers [ 28 ]. However, the UK did not track travel history as it was not considered valuable information in their testing criteria. This was problematic since people who traveled to COVID-19-occurring areas could have potentially acted as carriers of the virus to their respective communities and families, which might have strongly influenced the increasingly steep confirmed case curves. Neither the American, Brazilian nor Haitian governments considered a history of travel to a region of high COVID-19 incidence to be a high priority for testing, or to be an important criterion for suspected cases. Those with a travel history to high spread areas were only encouraged to seek testing if they developed a fever or respiratory symptoms. In direct contrast, the Chinese guidelines suggested that any travelers who traveled to a region or country with occurrence of COVID-19 must be tested, regardless of whether they had developed symptoms.

Although WHO provided a definition of symptoms observed in suspected cases that warranted further surveillance [ 11 ], it was a challenge to define the full clinical characteristics of COVID-19. Fever (> 38 °C), breathing problems, and chest radiographs showing bilateral lung infiltrates were the main clinical signs and symptoms reported during the outbreak [ 13 , 29 ]. For this reason, most countries considered fever, respiratory symptoms, and pneumonia as clinical justification for initiating diagnostic testing. Although by March/April 2020, the UK and US countries were defined as ‘ countries experiencing larger outbreaks ’ (as referred to in Group 4 of the WHO guidelines), they did appear to be largely acting in accordance with WHO advice at that point in time, despite not acting on the previous advice regarding the screening of travelers [ 11 ].

Although there was ample evidence of human-to-human transmission, the US and UK did not include contact with confirmed or suspected cases as screening criteria very early in the pandemic. The absence of this criteria early in the pandemic may have led to increased risk of viral spread. In contrast, South Korea undertook an intense contact-tracing program: upon confirmation of a COVID-19 case through laboratory testing, the South Korean government conducted interviews with the infected person, traced their travel history, used GPS phone tracking, and checked their credit-card history. The anonymized data detailing the travel history before diagnosis was published on a public website by the South Korean government. This allowed government officials to quickly release information about potential COVID-19 exposed locations and help people who may have been near those locations make quick decisions on whether they needed to be tested. Though effective, there were and continue to be concerns regarding individual privacy.

With the global spike of COVID-19 and consequent surge in suspected cases and geographic areas affected, the need for implementing screening criteria to better cope with each country’s capacity for screening and laboratory testing became increasingly evident. However, beyond supply chain issues with provision of testing kits, there were significant limitations of the government guidelines for COVID-19 testing in several domains. National health systems and coverage of COVID-19 medical expenses were vital to fostering a sense of financial certainty and a safe environment for those who were infected. Testing and treatment support came mainly or totally from the government in South Korea, the UK, China, and Brazil. All US citizens were covered for FDA-approved COVID-19 testing, regardless of private or federal insurance status, however, treatment coverage was subject to the insurer’s policy. Despite the larger role the governments took in most of the countries examined, Haiti’s COVID-19 health care response was primarily financially supported by the private sector (60%). Hospitals and newly established screening clinics from the private sector worked together with the Haitian Ministry of Health to screen Haitians, however health care facilities from the private sector were not regulated by government officials (hence the paucity of government screening guidelines) [ 30 ]. Given these limitations in testing capacity, WHO launched the ‘ COVID-Solidarity Response Fund for WHO’ to support COVID-19 rapid tests for low and middle-income countries [ 31 ].

In March 19, 2020, WHO recommended that “when symptomatic, patients are required to wait, ensure they have a separate waiting area” [ 32 ]. As an example of the increased preparedness the WHO called for, the South Korean government created temporary ‘ Public Relief Hospitals ’ which provided isolated treatment rooms for patients with respiratory and non-respiratory symptoms to ensure safe medical services to general patients and to prevent viral spread. Public Relief Hospitals were divided into two types: Type A and Type B. Both had separate outpatient treatment zones for patients without respiratory symptoms and for patients with respiratory symptoms but differed in whether their testing centers were contained within the hospital. The Korean government also permitted patients who have a chronic disease, but did not have any respiratory symptoms, to receive counseling and prescriptions by telephone or by proxy, therefore decreasing the risk of internal cross-infection within health care facilities for higher-risk patients. This approach was also utilized in the US and UK. In South Korea, non-respiratory patients, such as cancer patients or patients with heart problems, were directed to the general outpatient area at a Public Relief Hospital . Patients with mild respiratory symptoms were directed to see a doctor nearby, or to go to a respiratory outpatient area at a Public Relief Hospital . Suspected patients or PUI who developed COVID-19 symptoms were referred to a COVID-19 testing center after receiving guidance from a competent clinic or the 1339 call center. Using this triage workflow, Korean hospital systems were better able to prevent internal spreading of the COVID-19 virus in the hospitals and potentially reduced a higher infection-related risk of mortality across the population. The South Korean death rate provided evidence to support this hypothesis, showing that although they had a high rate of confirmed cases (10,780), the total number of deaths was only 250.

WHO recommended healthcare facilities limit the number of visits to suspected or confirmed COVID-19 patients by health care providers, family members, and visitors while being treated in health care facilities. WHO also suggested maintaining a record of all staff and visitors who entered suspected or confirmed COVID-19 patients’ rooms [ 32 ]. Even though the US’s federal guidance on hospital visitation seemed more liberal than other countries, especially when contrasted with South Korea and the UK, more restrictions were adopted depending on the local circumstances. For example, although limiting visitors was not advised by the US CDC until April, several hospitals in New York city restricted visitor access as early as March. Brazil’s government strongly recommended individuals with flu or respiratory symptoms are not allowed entry to the hospitals. The government also recommend the hospitals reduce visitor numbers, which, while not mandatory, was heavily implied to be. Although limitations of visitors were not mandatory, wearing a face mask was mandatory for all visitors in Haiti.

The figure illustrates the incidence of confirmed cases and deaths in six countries from January to April.

Despite being consistently recommended for use by symptomatic individuals and those in health-care settings, discrepancies were observed in the recommendations on wearing face masks in the general public and community settings. The WHO consistently maintained that the benefits of healthy people using masks in the community setting was not supported by the current evidence, and additionally could contribute to uncertainties or create critical risks [ 29 ]. This advice to decision makers remained in place up until the time of this paper submission in May 2020.

Several nations, such as the US and Brazil, changed their face cover recommendations as new studies were conducted that supported the use of face masks as an effective means to limit viral spread. Some studies may under-estimate their protective effects, while observational studies exaggerate them [ 33 ]. However, with the emerging evidence of asymptomatic or presymptomatic COVID-19 transmission, the authors note that the community guidance regarding utilizing a face mask and not sharing personal items could significantly prevent potential asymptomatic or presymptomatic transmission, which corroborates other publications [ 16 ]. Mask shortages were prevalent across countries in their early stage of use. For example, at the beginning of the pandemic, there was a mask shortage in South Korea due to mass panic-induced purchases by citizens. The South Korean government requested manufacturers increase mask production, and then ensured the newly manufactured masks were directly allocated to pharmacies where only a limited number of masks could be provided to individuals. The number of available masks was displayed in government- and private sector-created apps to prevent citizens from lining up outside pharmacies, which could have resulted in violating physical distancing measures. Additionally, the National Health Insurance Service database showed how many masks were sold to individuals per week.

Generally, the guidance provided across the six nations regarding avoiding infection by washing hands or using alcohol-based hand sanitizer frequently, performing respiratory etiquette when coughing or sneezing, and avoiding touching the face corroborated the WHO guidelines [ 34 ].

Despite physical distancing being vital to mitigating the spread of the novel coronavirus, political beliefs affected compliance with COVID-19 social distancing guidelines. This was especially evident in the US, where, in general, people who held contrasting political beliefs to the resident state governing body were less responsive to stay-at-home orders. For example, Republicans did not fully respect and react to stay-at-home orders when Democratic counties announced the order. In a similar fashion, Democrats were less likely to respond to stay-at-home orders when a Republican governor issued the decree [ 35 ].

On that point, it is worth noting that although the countries examined all referred to the government issued COVID-19 notices as ‘guidelines,’ these notices were not enforceable equally across countries. As an example, in the US, the CDC’s guidance acted as a framework that could be adapted for use by individual hospitals or by local/state governments for legislative purposes. However, in South Korea the guidelines essentially acted as enforceable legislation with serious financial repercussions.

Another important political development to note occurred in Brazil, when the Ministry of Health included a video on their website focused on clarifying “fake news” about the coronavirus. The video requested users confirm whether information presented in various medias was true before sharing that information with others. It also suggested individuals consult with an official number via WhatsApp for information clarification and communication.

An additional concern was raised regarding the use of health-tracking apps. Various countries used voluntary health-tracking apps to manage the COVID-19 pandemic either for informational, health vigilance, or contact tracing purposes. However, a unique aspect of the South Korean response was the mandate for all Koreans and long-term expatriates to install a health tracking app for contact tracing purposes. Privacy concerns were raised by several publications, some of whom referenced the possibility of preserving data protection [ 36 ], while others reflected on the legal implications and the need to refine the data into an aggregate, rather than individual-level data, to better deter the misuse of the data [ 37 ].

The countries’ guidelines on how to care for people infected with COVID-19 experiencing mild symptoms at home aligned with the WHO guidance [ 38 ]. According to the WHO, ensuring the sick person used a separate room and bathroom in the home would be essential to containing the virus, however, only the US, South Korea, and Brazil made this recommendation to their respective communities. Haiti, the UK, and China did not mention this recommendation in their guidelines. Although those suspected of contracting the coronavirus were requested to stay at home in the UK, limited information was provided to guide the home care process, such as how to disinfect the ill person’s room or how to handle sharing household items in the home. In China, all people suspected of having the coronavirus were instructed to seek testing at a testing center and were admitted to ‘Fangcang Shelter Hospitals.’ Therefore, it could be argued it was not necessary to provide information to the community on how to deal with sick people at home. The decision to advise all people suspected of having the coronavirus to go directly to the hospital is at odds with at least one study, which proposed that instead of guiding the COVID-19 patient to seek healthcare facilities, it would be preferable to provide at-home testing and monitoring [ 39 ]. However, while staying at home it is critical to carefully monitor worsening symptoms since medical care is not necessarily immediately available.

The symptom thresholds to contact healthcare providers varied between countries, with a wider array of symptoms (beyond the respiratory types) being included by countries that had dealt with the epidemic for longer periods of time. Clearly a great deal of clinical judgement was necessary for monitoring disease progression, since acting in a timely manner to differentiate a more serious case of COVID-19 was crucial to limiting fatality.

Finally, WHO provided information regarding the transportation of patients with confirmed and suspected COVID-19 to referral health care facilities, however, WHO did not give any information regarding transport mode to individuals with suspected COVID-19 [ 40 ]. The guidelines on transportation to healthcare facilities varied in emphasis between governments. A publication from China showed key involvement of public transportation in the dissemination of coronavirus. According to the study, the daily frequency of public transportation entrance and exit from Wuhan was significantly related to the number of COVID-19 cases in other cities [ 41 ]. When traveling to a hospital due to the presence of potential COVID-19 symptoms, wearing a face mask, using a personal vehicle, avoiding public transports and/or calling an ambulance were recommended by the Korean, US, and Chinese government’s guidelines. The UK and Haiti advised such patients utilize ambulance transport when heading to the hospital. The Brazilian government did not provided advice regarding transport mode.

Limitations

These findings are related to the guidelines for healthcare facilities and communities, as updated until April 20, 2020, however some guidelines may have been continuously updated beyond this date. In Haiti, because of the low prevalence of COVID-19 (total confirmed case: 100, deaths: 8 as of May 1, 2020), some information was unable to be obtained from the government guidelines, even though it was provided by news outlets or other medias, which were not included here. This study only used government guidelines accessible by the public, which may have limited the scope of the study’s usable information.

In summary, all six countries updated their guidelines, especially screening criteria, as the incidence of COVID-19 increased to take more aggressive actions against the progression of COVID-19 spread and to help “flatten the curve,” thus easing some of the burden on the respective healthcare systems. In the initial stages of the outbreak, certain strategies were universally employed to control the deadly virus’s spread, including quarantining the sick, contact tracing, and social distancing. However, these measures would have limited value if the people suspected of contracting the disease were not tested. It is difficult, if not impossible, to identify any one factor as the greatest cause for coronavirus dissemination, but by comparing these countries’ approaches it is possible to identify multiple factors that contribute to an overall effective strategy for reducing its spread. Additionally, there are multiple characteristics that influence the prevalence and incidence of COVID-19, including population density, differences in healthcare infrastructure, and primary means of transportation. Future studies should focus in more detail on these factors and their influence on the prevalence and incidence of COVID-19.

Abbreviations

Coronavirus disease

Computed Tomography

Center for Disease Control and Prevention

Emergency room

Food and Drug Administration

Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

Intensive care unit

Korea Centers for Disease Control and Prevention

Middle East respiratory syndrome

National Health Service

Patient Under Investigation

Personal Protective Equipment

United States

United Kingdom

World Health Organization

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Acknowledgements

Samia Valeria Ozorio Dutra acknowledges support from the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES) for graduate education.

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Ji Youn Yoo and Samia Valeria Ozorio Dutra contributed equally to this work.

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College of Nursing, University of South Florida, 12901 Bruce B. Downs Blvd, Tampa, FL, 33612, USA

Ji Youn Yoo & Maureen Groer

College of Nursing, University of Tennessee – Knoxville, 1200 Volunteer Blvd, Knoxville, TN, 37902, USA

Samia Valeria Ozorio Dutra

College of Nursing, University of Florida, Health Professions, Nursing, Pharmacy Building, 1225 Center Dr, Gainesville, FL, 32603, USA

Dany Fanfan

Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 78, Tampa, FL, 33612, USA

Sarah Sniffen

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Jamile Siddiqui

Department of Emergency Medical Service, Daejeon Health Institute of Technology, 21 Chungjeong St., Dong-gu, Daejeon, 34504, Republic of Korea

Hyo-Suk Song

Department of Special Warfare Medical Non-Commissioned Officer, Daejeon Health Institute of Technology, 21 Chungjeong St., Dong-gu, Daejeon, 34504, Republic of Korea

Sung Hwan Bang

Department of Disaster Construction Safety, Daejeon Health Institute of Technology, 21 Chungjeong St., Dong-gu, Daejeon, 34504, Republic of Korea

Dong Eun Kim

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Yoo, J., Dutra, S.V.O., Fanfan, D. et al. Comparative analysis of COVID-19 guidelines from six countries: a qualitative study on the US, China, South Korea, the UK, Brazil, and Haiti. BMC Public Health 20 , 1853 (2020). https://doi.org/10.1186/s12889-020-09924-7

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How to Protect Yourself and Others

CDC’s Respiratory Virus Guidance  provides strategies you can use to help protect yourself and others from health risks caused by COVID-19 and other respiratory viruses. These actions can help you lower the risk of COVID-19 transmission (spreading or catching COVID-19) and lower the risk of severe illness if you get sick.

Core Prevention Strategies

CDC recommends that all people use core prevention strategies to protect themselves and others from COVID-19:

• Although vaccinated people sometimes get infected with the virus that causes COVID-19, staying up to date on COVID-19 vaccines significantly lowers the risk of getting very sick, being hospitalized, or dying from COVID-19.
• Practice good hygiene  (practices that improve cleanliness)
• Take steps for cleaner air

When you are sick:

• Learn when you can go back to your normal activities .
• Seek health care promptly for testing and/or treatment if you have risk factors for severe illness . Treatment may help lower your risk of severe illness, but it needs to be started within a few days of when your symptoms begin.

Additional Prevention Strategies

In addition, there are other prevention strategies that you can choose to further protect yourself and others.

• Wearing a mask and putting distance between yourself and others  can help lower the risk of COVID-19 transmission.
• Testing for COVID-19 can help you decide what to do next, like getting treatment to reduce your risk of severe illness and taking steps  to lower your chances of spreading COVID-19 to others.

Key Times for Prevention

Using these prevention strategies can be especially helpful when:

• Respiratory viruses, such as COVID-19, flu, and RSV, are causing a lot of illness in your community
• You or those around you have risk factors  for severe illness
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Find out if respiratory viruses are causing a lot of illness in your community. Data updated weekly.

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Effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality: systematic review and meta-analysis

Linked editorial.

Public health measures for covid-19

• Related content
• Peer review
• Stella Talic , lecturer in clinical epidemiology and public health 1 2 ,
• Shivangi Shah , honours student 1 ,
• Holly Wild , lecturer and honours student 1 3 ,
• Danijela Gasevic , senior lecturer in epidemiology and chronic disease prevention 1 4 ,
• Ashika Maharaj , lecturer quality and safety and cancer epidemiology 1 ,
• Zanfina Ademi , associate professor of medical outcomes and health economics 1 2 ,
• Xue Li , assistant professor 4 6 ,
• Wei Xu , research student 4 ,
• Ines Mesa-Eguiagaray , statistical geneticist 4 ,
• Jasmin Rostron , research student 4 ,
• Evropi Theodoratou , professor of cancer epidemiology and global health 4 5 ,
• Xiaomeng Zhang , research student 4 ,
• Ashmika Motee , research student 4 ,
• Danny Liew , professor of medical outcomes and health economics 1 2 ,
• Dragan Ilic , professor of medical education and public health 1
• 1 School of Public Health and Preventive Medicine, Monash University, Melbourne, 3004 VIC, Australia
• 2 Monash Outcomes Research and health Economics (MORE) Unit, Monash University, VIC, Australia
• 3 Torrens University, VIC, Australia
• 4 Centre for Global Health, The Usher Institute, University of Edinburgh, Edinburgh, UK
• 5 Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
• 6 School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
• Correspondence to: S Talic stella.talic{at}monash.edu
• Accepted 21 October 2021

Objective To review the evidence on the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality.

Design Systematic review and meta-analysis.

Data sources Medline, Embase, CINAHL, Biosis, Joanna Briggs, Global Health, and World Health Organization COVID-19 database (preprints).

Eligibility criteria for study selection Observational and interventional studies that assessed the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality.

Main outcome measures The main outcome measure was incidence of covid-19. Secondary outcomes included SARS-CoV-2 transmission and covid-19 mortality.

Data synthesis DerSimonian Laird random effects meta-analysis was performed to investigate the effect of mask wearing, handwashing, and physical distancing measures on incidence of covid-19. Pooled effect estimates with corresponding 95% confidence intervals were computed, and heterogeneity among studies was assessed using Cochran’s Q test and the I 2 metrics, with two tailed P values.

Results 72 studies met the inclusion criteria, of which 35 evaluated individual public health measures and 37 assessed multiple public health measures as a “package of interventions.” Eight of 35 studies were included in the meta-analysis, which indicated a reduction in incidence of covid-19 associated with handwashing (relative risk 0.47, 95% confidence interval 0.19 to 1.12, I 2 =12%), mask wearing (0.47, 0.29 to 0.75, I 2 =84%), and physical distancing (0.75, 0.59 to 0.95, I 2 =87%). Owing to heterogeneity of the studies, meta-analysis was not possible for the outcomes of quarantine and isolation, universal lockdowns, and closures of borders, schools, and workplaces. The effects of these interventions were synthesised descriptively.

Conclusions This systematic review and meta-analysis suggests that several personal protective and social measures, including handwashing, mask wearing, and physical distancing are associated with reductions in the incidence covid-19. Public health efforts to implement public health measures should consider community health and sociocultural needs, and future research is needed to better understand the effectiveness of public health measures in the context of covid-19 vaccination.

Systematic review registration PROSPERO CRD42020178692.

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Introduction

The impact of SARS-CoV-2 on global public health and economies has been profound. 1 As of 14 October 2021, there were 239 007 759 million cases of confirmed covid-19 and 4 871 841 million deaths with covid-19 worldwide. 2

A variety of containment and mitigation strategies have been adopted to adequately respond to covid-19, with the intention of deferring major surges of patients in hospitals and protecting the most vulnerable people from infection, including elderly people and those with comorbidities. 3 Strategies to achieve these goals are diverse, commonly based on national risk assessments that include estimation of numbers of patients requiring hospital admission and availability of hospital beds and ventilation support.

Globally, vaccination programmes have proved to be safe and effective and save lives. 4 5 Yet most vaccines do not confer 100% protection, and it is not known how vaccines will prevent future transmission of SARS-CoV-2, 6 given emerging variants. 7 8 9 The proportion of the population that must be vaccinated against covid-19 to reach herd immunity depends greatly on current and future variants. 10 This vaccination threshold varies according to the country and population’s response, types of vaccines, groups prioritised for vaccination, and viral mutations, among other factors. 6 Until herd immunity to covid-19 is reached, regardless of the already proven high vaccination rates, 11 public health preventive strategies are likely to remain as first choice measures in disease prevention, 12 particularly in places with a low uptake of covid-19 vaccination. Measures such as lockdown (local and national variant), physical distancing, mandatory use of face masks, and hand hygiene have been implemented as primary preventive strategies to curb the covid-19 pandemic. 13

Public health (or non-pharmaceutical) interventions have been shown to be beneficial in fighting respiratory infections transmitted through contact, droplets, and aerosols. 14 15 Given that SARS-CoV-2 is highly transmissible, it is a challenge to determine which measures might be more effective and sustainable for further prevention.

Substantial benefits in reducing mortality were observed in countries with universal lockdowns in place, such as Australia, New Zealand, Singapore, and China. Universal lockdowns are not, however, sustainable, and more tailored interventions need to be considered; the ones that maintain social lives and keep economies functional while protecting high risk individuals. 16 17 Substantial variation exists in how different countries and governments have applied public health measures, 18 and it has proved a challenge for assessing the effectiveness of individual public health measures, particularly in policy decision making. 19

Previous systematic reviews on the effectiveness of public health measures to treat covid-19 lacked the inclusion of analytical studies, 20 a comprehensive approach to data synthesis (focusing only on one measure), 21 a rigorous assessment of effectiveness of public health measures, 22 an assessment of the certainty of the evidence, 23 and robust methods for comparative analysis. 24 To tackle these gaps, we performed a systematic review of the evidence on the effectiveness of both individual and multiple public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality. When feasible we also did a critical appraisal of the evidence and meta-analysis.

This systematic review and meta-analysis were conducted in accordance with PRISMA 25 (supplementary material 1, table 1) and with PROSPERO (supplementary material 1, table 2).

Eligibility criteria

Articles that met the population, intervention, comparison, outcome, and study design criteria were eligible for inclusion in this systematic review (supplementary material 1, table 3). Specifically, preventive public health measures that were tested independently were included in the main analysis. Multiple measures, which generally contain a “package of interventions”, were included as supplementary material owing to the inability to report on the individual effectiveness of measures and comparisons on which package led to enhanced outcomes. The public health measures were identified from published World Health Organization sources that reported on the effectiveness of such measures on a range of communicable diseases, mostly respiratory infections, such as influenza.

Given that the scientific community is concerned about the ability of the numerous mathematical models, which are based on assumptions, to predict the course of virus transmission or effectiveness of interventions, 26 this review focused only on empirical studies. We excluded case reports and case studies, modelling and simulation studies, studies that provided a graphical summary of measures without clear statistical assessments or outputs, ecological studies that provided a descriptive summary of the measures without assessing linearity or having comparators, non‐empirical studies (eg, commentaries, editorials, government reports), other reviews, articles involving only individuals exposed to other pathogens that can cause respiratory infections, such as severe acute respiratory syndrome or Middle East respiratory syndrome, and articles in a language other than English.

Information sources

We carried out electronic searches of Medline, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature, Ebsco), Global Health, Biosis, Joanna Briggs, and the WHO COVID-19 database (for preprints). A clinical epidemiologist (ST) developed the initial search strategy, which was validated by two senior medical librarians (LR and MD) (supplementary material 1, table 4). The updated search strategy was last performed on 7 June 2021. All citations identified from the database searches were uploaded to Covidence, an online software designed for managing systematic reviews, 27 for study selection.

Study selection

Authors ST, DG, SS, AM, ET, JR, XL, WX, IME, and XZ independently screened the titles and abstracts and excluded studies that did not match the inclusion criteria. Discrepancies were resolved in discussion with the main author (ST). The same authors retrieved full text articles and determined whether to include or exclude studies on the basis of predetermined selection criteria. Using a pilot tested data extraction form, authors ST, SS, AM, JR, XL, WX, AM, IME, and XZ independently extracted data on study design, intervention, effect measures, outcomes, results, and limitations. ST, SS, AM, and HW verified the extracted data. Table 5 in supplementary material 1 provides the specific criteria used to assess study designs. Given the heterogeneity and diversity in how studies defined public health measures, we took a common approach to summarise evidence of these interventions (supplementary material 1, table 6).

Risk of bias within individual studies

SS, JR, XL, WX, IME, and XZ independently assessed risk of bias for each study, which was cross checked by ST and HW. For non-interventional observational studies, a ROBINS-I (risk of bias in non-randomised studies of interventions) risk of bias tool was used. 28 For interventional studies, a revised tool for assessing risk of bias in randomised trials (RoB 2) tool was used. 29 Reviewers rated each domain for overall risk of bias as low, moderate, high, or serious/critical.

Data synthesis

The DerSimonian and Laird method was used for random effects meta-analysis, in which the standard error of the study specific estimates was adjusted to incorporate a measure of the extent of variation, or heterogeneity, among the effects observed for public health measures across different studies. It was assumed that the differences between studies are a result of different, yet related, intervention effects being estimated. If fewer than five studies were included in meta-analysis, we applied a recommended modified Hartung-Knapp-Sidik-Jonkman method. 30

Statistical analysis

Because of the differences in the effect metrics reported by the included studies, we could only perform quantitative data synthesis for three interventions: handwashing, face mask wearing, and physical distancing. Odds ratios or relative risks with corresponding 95% confidence intervals were reported for the associations between the public health measures and incidence of covid-19. When necessary, we transformed effect metrics derived from different studies to allow pooled analysis. We used the Dersimonian Laird random effects model to estimate pooled effect estimates along with corresponding 95% confidence intervals for each measure. Heterogeneity among individual studies was assessed using the Cochran Q test and the I 2 test. 31 All statistical analyses were conducted in R (version 4.0.3) and all P values were two tailed, with P=0.05 considered to be significant. For the remaining studies, when meta-analysis was not feasible, we reported the results in a narrative synthesis.

Public and patient involvement

No patients or members of the public were directly involved in this study as no primary data were collected. A member of the public was, however, asked to read the manuscript after submission.

A total of 36 729 studies were initially screened, of which 36 079 were considered irrelevent. After exclusions, 650 studies were eligible for full text review and 72 met the inclusion criteria. Of these studies, 35 assessed individual interventions and were included in the final synthesis of results ( fig 1 ) and 37 assessed multiple interventions as a package and are included in supplementary material 3, tables 2 and 3. The included studies comprised 34 observational studies and one interventional study, eight of which were included in the meta-analysis.

Flow of articles through the review. WHO=World Health Organization

Risk of bias

According to the ROBINS-I tool, 28 the risk of bias was rated as low in three studies, 32 33 34 moderate in 24 studies, 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 and high to serious in seven studies. 59 60 61 62 63 64 65 One important source of serious or critical risk of bias in most of the included studies was major confounding, which was difficult to control for because of the novel nature of the pandemic (ie, natural settings in which multiple interventions might have been enforced at once, different levels of enforcement across regions, and uncaptured individual level interventions such as increased personal hygiene). Variations in testing capacity and coverage, changes to diagnostic criteria, and access to accurate and reliable outcome data on covid-19 incidence and covid-19 mortality, was a source of measurement bias for numerous studies ( fig 2 ). These limitations were particularly prominent early in the pandemic, and in low income environments. 47 52 62 63 65 The randomised controlled trial 66 was rated as moderate risk of bias according to the ROB-2 tool. Missing data, losses to follow-up, lack of blinding, and low adherence to intervention all contributed to the reported moderate risk. Tables 1 and 2 in supplementary material 2 summarise the risk of bias assessment for each study assessing individual measures.

Summary of risk of bias across studies assessing individual measures using risk of bias in non-randomised studies of interventions (ROBINS-I) tool

Study characteristics

Studies assessing individual measures.

Thirty five studies provided estimates on the effectiveness of an individual public health measures. The studies were conducted in Asia (n=11), the United States (n=9), Europe (n=7), the Middle East (n=3), Africa (n=3), South America (n=1), and Australia (n=1). Thirty four of the studies were observational and one was a randomised controlled trial. The study designs of the observational studies comprised natural experiments (n=11), quasi-experiments (n=3), a prospective cohort (n=1), retrospective cohorts (n=8), case-control (n=2), and cross sectional (n=9). Twenty six studies assessed social measures, 32 34 35 37 38 39 40 41 42 44 46 47 48 52 53 55 56 57 58 59 60 61 63 64 65 67 12 studies assessed personal protective measures, 36 43 45 49 50 57 58 60 63 66 68 three studies assessed travel related measures, 54 58 62 and one study assessed environmental measures 57 (some interventions overlapped across studies). The most commonly measured outcome was incidence of covid-19 (n=18), followed by SARS-CoV-2 transmission, measured as reproductive number, growth number, or epidemic doubling time (n=13), and covid-19 mortality (n=8). Table 1 in supplementary material 3 provides detailed information on each study.

Effects of interventions

Personal protective measures.

Handwashing and covid-19 incidence —Three studies with a total of 292 people infected with SARS-CoV-2 and 10 345 participants were included in the analysis of the effect of handwashing on incidence of covid-19. 36 60 63 Overall pooled analysis suggested an estimated 53% non-statistically significant reduction in covid-19 incidence (relative risk 0.47, 95% confidence interval 0.19 to 1.12, I 2 =12%) ( fig 3 ). A sensitivity analysis without adjustment showed a significant reduction in covid-19 incidence (0.49, 0.33 to 0.72, I 2 =12%) ( fig 4 ). Risk of bias across the three studies ranged from moderate 36 60 to serious or critical 63 ( fig 2 ).

Meta-analysis of evidence on association between handwashing and incidence of covid-19 using modified Hartung-Knapp-Sidik-Jonkman adjusted random effect model

Meta-analysis of evidence on association between handwashing and incidence of covid-19 using unadjusted random effect model

Mask wearing and covid-19 incidence —Six studies with a total of 2627 people with covid-19 and 389 228 participants were included in the analysis examining the effect of mask wearing on incidence of covid-19 ( table 1 ). 36 43 57 60 63 66 Overall pooled analysis showed a 53% reduction in covid-19 incidence (0.47, 0.29 to 0.75), although heterogeneity between studies was substantial (I 2 =84%) ( fig 5 ). Risk of bias across the six studies ranged from moderate 36 57 60 66 to serious or critical 43 63 ( fig 2 ).

Study characteristics and main results from studies that assessed individual personal protective and environmental measures

• View inline

Meta-analysis of evidence on association between mask wearing and incidence of covid-19 using unadjusted random effect model

Mask wearing and transmission of SARS-CoV-2, covid-19 incidence, and covid-19 mortality —The results of additional studies that assessed mask wearing (not included in the meta-analysis because of substantial differences in the assessed outcomes) indicate a reduction in covid-19 incidence, SARS-CoV-2 transmission, and covid-19 mortality. Specifically, a natural experiment across 200 countries showed 45.7% fewer covid-19 related mortality in countries where mask wearing was mandatory ( table 1 ). 49 Another natural experiment study in the US reported a 29% reduction in SARS-CoV-2 transmission (measured as the time varying reproductive number Rt) (risk ratio 0.71, 95% confidence interval 0.58 to 0.75) in states where mask wearing was mandatory. 58

A comparative study in the Hong Kong Special Administrative Region reported a statistically significant lower cumulative incidence of covid-19 associated with mask wearing than in selected countries where mask wearing was not mandatory ( table 1 ). 68 Similarly, another natural experiment involving 15 US states reported a 2% statistically significant daily decrease in covid-19 transmission (measured as case growth rate) at ≥21 days after mask wearing became mandatory, 50 whereas a cross sectional study reported that a 10% increase in self-reported mask wearing was associated with greater odds for control of SARS-CoV-2 transmission (adjusted odds ratio 3.53, 95% confidence interval 2.03 to 6.43). 45 The five studies were rated at moderate risk of bias ( fig 2 ).

Environmental measures

Disinfection in household and covid-19 incidence.

Only one study, from China, reported the association between disinfection of surfaces and risk of secondary transmission of SARS-CoV-2 within households ( table 1 ). 57 The study assessed disinfection retrospectively by asking participants about their “daily use of chlorine or ethanol-based disinfectant in households,” and observed that use of disinfectant was 77% effective at reducing SARS-CoV-2 transmission (odds ratio 0.23, 95% confidence interval 0.07 to 0.84). The study did not collect data on the concentration of the disinfectant used by participants and was rated at moderate risk of bias ( fig 2 ).

Social measures

Physical distancing and covid-19 incidence.

Five studies with a total of 2727 people with SARS-CoV-2 and 108 933 participants were included in the analysis that examined the effect of physical distancing on the incidence of covid-19. 37 53 57 60 63 Overall pooled analysis indicated a 25% reduction in incidence of covid-19 (relative risk 0.75, 95% confidence interval 0.59 to 0.95, I 2 =87%) ( fig 6 ). Heterogeneity among studies was substantial, and risk of bias ranged from moderate 37 53 57 60 to serious or critical 63 ( fig 2 ).

Meta-analysis of evidence on association between physical distancing and incidence of covid-19 using unadjusted random effect model

Physical distancing and transmission of SARS-CoV-2 and covid-19 mortality

Studies that assessed physical distancing but were not included in the meta-analysis because of substantial differences in outcomes assessed, generally reported a positive effect of physical distancing ( table 2 ). A natural experiment from the US reported a 12% decrease in SARS-CoV-2 transmission (relative risk 0.88, 95% confidence interval 0.86 to 0.89), 40 and a quasi-experimental study from Iran reported a reduction in covid-19 related mortality (β −0.07, 95% confidence interval −0.05 to −0.10; P<0.001). 47 Another comparative study in Kenya also reported a reduction in transmission of SARS-CoV-2 after physical distancing was implemented, reporting 62% reduction in overall physical contacts (reproductive number pre-intervention was 2.64 and post-intervention was 0.60 (interquartile range 0.50 to 0.68)). 61 These three studies were rated at moderate risk of bias 40 61 to serious or critical risk of bias 47 ( fig 2 ).

Study characteristics and main results from studies assessing individual social measures

Stay at home or isolation and transmission of SARS-CoV-2

All the studies that assessed stay at home or isolation measures reported reductions in transmission of SARS-CoV-2 ( table 2 ). A retrospective cohort study from the US reported a significant reduction in the odds of having a positive reproductive number (R0) result (odds ratio 0.07, 95% confidence interval 0.01 to 0.37), 41 and a natural experiment reported a 51% reduction in time varying reproductive number (Rt) (risk ratio 0.49, 95% confidence interval 0.43 to 0.54). 58

A study from the UK reported a 74% reduction in the average daily number of contacts observed for each participant and estimated a decrease in reproductive number: the reproductive number pre-intervention was 3.6 and post-intervention was 0.60 (95% confidence interval 0.37 to 0.89). 65 Similarly, an Iranian study projected the reproductive number using serial interval distribution and the number of incidence cases and found a significant decrease: the reproductive number pre-intervention was 2.70 and post-intervention was 1.13 (95% confidence interval 1.03 to 1.25). 55 Three of the studies were rated at moderate to serious or critical risk of bias, 55 58 65 and one study was rated at low risk of bias 41 ( fig 2 ).

Quarantine and incidence and transmission of SARS-CoV-2

Quarantine was assessed in two studies ( table 2 ). 34 59 A prospective cohort study from Saudi Arabia reported a 4.9% decrease in the incidence of covid-19 at eight weeks after the implementation of quarantine. 34 This study was rated at low risk of bias ( fig 2 ). A retrospective cohort study from India reported a 14 times higher risk of SARS-CoV-2 transmission associated with no quarantine compared with strict quarantine (odds ratio 14.44, 95% confidence interval 2.42 to 86.17). 59 This study was rated at moderate risk of bias ( fig 2 ).

School closures and covid-19 incidence and covid-19 mortality

Two studies assessed the effectiveness of school closures on transmission of SARS-CoV-2, incidence of covid-19, or covid-19 mortality ( table 2 ). 44 48 A US population based longitudinal study reported on the effectiveness of state-wide closure of primary and secondary schools and observed a 62% decrease (95% confidence interval −49% to −71%) in incidence of covid-19 and a 58% decrease (−46% to−68%) in covid-19 mortality. 48 Conversely, a natural experiment from Japan reported no effect of school closures on incidence of covid-19 (α coefficient 0.08, 95% confidence interval −0.36 to 0.65). 44 Both studies were rated at moderate risk of bias ( fig 2 ).

School closures and transmission of SARS-CoV-2

Two natural experiments from the US reported a reduction in transmission (ie, reproductive number); with one study reporting a reduction of 13% (relative risk 0.87, 95% confidence interval 0.86 to 0.89) 40 and another reporting a 10% (0.90, 0.86 to 0.93) reduction ( table 2 ). 58 A Swedish study reported an association between school closures and a small increase in confirmed SARS-CoV-2 infections in parents (odds ratio 1.17, 95% confidence interval 1.03 to 1.32), but observed that teachers in lower secondary schools were twice as likely to become infected than teachers in upper secondary schools (2.01, 1.52 to 2.67). 32 All three studies were rated at moderate risk of bias ( fig 2 ).

Business closures and transmission of SARS-CoV-2

Two natural experiment studies assessed business closures across 50 US states and reported reductions in transmission of SARS-CoV-2 ( table 2 ). 40 58 One of the studies observed a significant reduction in transmission of 12% (relative risk 0.88, 95% confidence interval 0.86 to 0.89) 40 and the other reported a significant 16% (risk ratio 0.84, 0.79 to 0.90) reduction. 58 Both studies were rated at moderate risk of bias ( fig 2 ).

Lockdown and incidence of covid-19

A natural experiment involving 202 countries suggested that countries that implemented universal lockdown had fewer new cases of covid-19 than countries that did not (β coefficient −235.8 (standard error −11.04), P<0.01) ( table 2 ). 52 An Indian quasi-experimental study reported a 10.8% reduction in incidence of covid-19 post-lockdown, 56 whereas a South African retrospective cohort study observed a 14.1% reduction in risk after implementation of universal lockdown ( table 2 ). 46 These studies were rated at high risk of bias 52 and moderate risk of bias 46 56 ( fig 2 ).

Lockdown and covid-19 mortality

The three studies that assessed universal lockdown and covid-19 mortality generally reported a decrease in mortality ( table 2 ). 35 38 42 A natural experiment study involving 45 US states reported a decrease in covid-19 related mortality of 2.0% (95% confidence interval −3.0% to 0.9%) daily after lockdown had been made mandatory. 35 A Brazilian quasi-experimental study reported a 27.4% average difference in covid-19 related mortality rates in the first 25 days of lockdown. 42 In addition, a natural experiment study reported about 30% and 60% reductions in covid-19 related mortality post-lockdown in Italy and Spain over four weeks post-intervention, respectively. 38 All three studies were rated at moderate risk of bias ( fig 2 ).

Lockdown and transmission of SARS-CoV-2

Four studies assessed universal lockdown and transmission of SARS-CoV-2 during the first few months of the pandemic ( table 2 ). The decrease in reproductive number (R0) ranged from 1.27 in Italy (pre-intervention 2.03, post-intervention 0.76) 39 to 2.09 in India (pre-intervention 3.36, post-intervention 1.27), 64 and 3.97 in China (pre-intervention 4.95, post-intervention 0.98). 33 A natural experiment from the US reported that lockdown was associated with an 11% reduction in transmission of SARS-CoV-2 (relative risk 0.89, 95% confidence interval 0.88 to 0.91). 40 All the studies were rated at low risk of bias 33 39 to moderate risk 40 64 ( fig 2 ).

Travel related measures

Restricted travel and border closures.

Border closure was assessed in one natural experiment study involving nine African countries ( table 3 ). 62 Overall, the countries recorded an increase in the incidence of covid-19 after border closure. These studies concluded that the implementation of border closures within African countries had minimal effect on the incidence of covid-19. The study had important limitations and was rated at serious or critical risk of bias. In the US, a natural experiment study reported that restrictions on travel between states contributed about 11% to a reduction in SARS-CoV-2 transmission ( table 3 ). 36 The study was rated at moderate risk of bias ( fig 2 ).

Study characteristics and main results from studies that assessed individual travel measures

Entry and exit screening (virus or symptom screening)

One retrospective cohort study assessed screening of symptoms, which involved testing 65 000 people for fever ( table 3 ). 54 The study found that screening for fever lacked sensitivity (ranging from 18% to 24%) in detecting people with SARS-CoV-2 infection. This translated to 86% of the population with SARS-CoV-2 remaining undetected when screening for fever. The study was rated at moderate risk of bias ( fig 2 ).

Multiple public health measures

Overall, 37 studies provided estimates on the effectiveness of multiple public health measures, assessed as a collective group. Studies were mostly conducted in Asia (n=15), the US (n=11), Europe (n=6), Africa (n=4), and South America (n=1). All the studies were observational. The most commonly measured outcome was transmission of disease (ie, measured as reproductive number, growth number, or epidemic doubling time) (n=23), followed by covid-19 incidence (n=19) and covid-19 mortality (n=8). This review attempted to assess the overall effectiveness of the public health intervention packages by reporting the percentage difference in outcome before and after implementation of measures or between regions or countries studied. Eleven of the 37 included studies noted a difference of between 26% and 50% in transmission of SARS-CoV-2 and incidence of covid-19, 70 71 72 73 74 75 76 77 78 79 80 nine noted a difference of between 51% and 75% in SARS-CoV-2 transmission, covid-19 incidence, and covid-19 mortality, 81 82 83 84 85 86 87 88 89 and 14 noted a difference of more than 75% in transmission of SARS-CoV-2, covid-19 incidence and covid-19 mortality. 79 80 89 90 91 92 93 94 95 96 97 98 99 100 For the remaining studies, the overall effectiveness was not assessed owing to a lack of comparators (see supplementary material 3, table 3). Two studies that assessed universal lockdown and physical distancing reported a decrease of between 0% and 25% in SARS-CoV-2 transmission and covid-19 incidence. 79 101 Studies that included school and workplace closures, 91 95 96 isolation or stay at home measures, 80 94 or a combination of both 79 89 93 97 98 99 reported decreases of more than 75% in SARS-CoV-2 transmission. Supplementary material 3, table 2 provides detailed information on each study.

Worldwide, government and public health organisations are mitigating the spread of SARS-CoV-2 by implementing various public health measures. This systematic review identified a statistically significant reduction in the incidence of covid-19 through the implementation of mask wearing and physical distancing. Handwashing interventions also indicated a substantial reduction in covid-19 incidence, albeit not statistically significant in the adjusted model. As the random effects model tends to underestimate confidence intervals when a meta-analysis includes a small number of individual studies (<5), the adjusted model for handwashing showed a statistically non-significant association in reducing the incidence of covid-19 compared with the unadjusted model.

Overall effectiveness of these interventions was affected by clinical heterogeneity and methodological limitations, such as confounding and measurement bias. It was not possible to evaluate the impact of type of face maks (eg, surgical, fabric, N95 respirators) and compliance and frequency of wearing masks owing to a lack of data. Similarly, it was not feasible to assess the differences in effect that different recommendations for physical distancing (ie, 1.5 m, 2m, or 3 m) have as preventive strategies.

The effectiveness of measures such as universal lockdowns and closures of businesses and schools for the containment of covid-19 have largely been effective, but depended on early implementation when incidence rates of covid-19 were still low. 42 52 58 Only Japan reported no decrease in covid-19 incidence after school closures, 44 and other studies found that different public health measures were sometimes implemented simultaneously or soon after one another, thus the results should be interpreted with caution. 32 46 56

Isolation or stay at home was an effective measure in reducing the transmission of SARS-CoV-2, but the included studies used results for mobility to assess stay at home or isolation and therefore could have been limited by potential flaws in publicly available phone data, 41 58 102 and variations in the enforcement of public health measures in different states or regions were not assessed. 55 58 102 Quarantine was found to be as effective in reducing the incidence of covid-19 and transmission of SARS-CoV-2, yet variation in testing and case detection in low income environments was substantial. 59 96 98 Another study reported that quarantine was effective in reducing the transmission of SARS-CoV-2 in a cohort with a low prevalence of the virus, yet it is unknown if the same effect would be observed with higher prevalence. 34

It was not possible to draw conclusions about the effectiveness of restricted travel and full border closures because the number of empirical studies was insufficient. Single studies identified that border closure in Africa had a minimal effect in reducing SARS-CoV-2 transmission, but the study was assessed as being at high risk of bias. 62 Screening for fever was also identified to be ineffective, with only 24% of positive cases being captured by screening. 54

Comparison with other studies

Previous literature reviews have identified mask wearing as an effective measure for the containment of SARS-CoV-2 103 ; the caveat being that more high level evidence is required to provide unequivocal support for the effectiveness of the universal use of face masks. 104 105 Additional empirical evidence from a recent randomised controlled trial (originally published as a preprint) indicates that mask wearing achieved a 9.3% reduction in seroprevalence of symptomatic SARS-CoV-2 infection and an 11.9% reduction in the prevalence of covid-19-like symptoms. 106 Another systematic review showed stronger effectiveness with the use of N95, or similar, respirators than disposable surgical masks, 107 and a study evaluating the protection offered by 18 different types of fabric masks found substantial heterogeneity in protection, with the most effective mask being multilayered and tight fitting. 108 However, transmission of SARS-CoV-2 largely arises in hospital settings in which full personal protective measures are in place, which suggests that when viral load is at its highest, even the best performing face masks might not provide adequate protection. 51 Additionally, most studies that assessed mask wearing were prone to important confounding bias, which might have altered the conclusions drawn from this review (ie, effect estimates might have been underestimated or overestimated or can be related to other measures that were in place at the time the studies were conducted). Thus, the extent of such limitations on the conclusions drawn remain unknown.

A 2020 rapid review concluded that quarantine is largely effective in reducing the incidence of covid-19 and covid-19 mortality. However, uncertainty over the magnitude of such an effect still remains, 109 with enhanced management of quality quarantine facilities for improved effective control of the epidemics urgently needed. 110 In addition, findings on the application of school and workplace closures are still inconclusive. Policy makers should be aware of the ambiguous evidence when considering school closures, as other potentially less disruptive physical distancing interventions might be more appropriate. 21 Numerous findings from studies on the efficacy of school closures showed that the risk of transmission within the educational environment often strongly depends on the incidence of covid-19 in the community, and that school closures are most successfully associated with control of SARS-CoV-2 transmission when other mitigation strategies are in place in the community. 111 112 113 114 115 116 117 School closures have been reported to be disruptive to students globally and are likely to impair children’s social, psychological, and educational development 118 119 and to result in loss of income and productivity in adults who cannot work because of childcare responsibilities. 120

Speculation remains as how best to implement physical distancing measures. 121 Studies that assess physical distancing measures might interchangeably study physical distancing with lockdown 35 52 56 64 and other measures and thus direct associations are difficult to assess.

Empirical evidence from restricted travel and full border closures is also limited, as it is almost impossible to study these strategies as single measures. Current evidence from a recent narrative literature review suggested that control of movement, along with mandated quarantine, travel restrictions, and restricting nationals from entering areas of high infection, are effective measures, but only with good compliance. 122 A narrative literature review of travel bans, partial lockdowns, and quarantine also suggested effectiveness of these measures, 123 and another rapid review further supported travel restrictions and cross border restrictions to stop the spread of SARS-CoV-2. 124 It was impossible to make such observations in the current review because of limited evidence. A German review, however, suggested that entry, exit, and symptom screening measures to prevent transmission of SARS-CoV-2 are not effective at detecting a meaningful proportion of cases, 125 and another review using real world data from multiple countries found that border closures had minimal impact on the control of covid-19. 126

Although universal lockdowns have shown a protective effect in lowering the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality, these measures are also disruptive to the psychosocial and mental health of children and adolescents, 127 global economies, 128 and societies. 129 Partial lockdowns could be an alternative, as the associated effectiveness can be high, 125 especially when implemented early in an outbreak, 85 and such measures would be less disruptive to the general population.

It is important to also consider numerous sociopolitical and socioeconomic factors that have been shown to increase SARS-CoV-2 infection 130 131 and covid-19 mortality. 132 Immigration status, 82 economic status, 81 101 and poverty and rurality 98 can influence individual and community compliance with public health measures. Poverty can impact the ability of communities to physically distance, 133 especially in crowded living environments, 134 135 as well as reduce access to personal protective measures. 134 135 A recent study highlights that “a one size fits all” approach to public health measures might not be effective at reducing the spread of SARS-CoV-2 in vulnerable communities 136 and could exacerbate social and economic inequalities. 135 137 As such, a more nuanced and community specific approach might be required. Even though screening is highly recommended by WHO 138 because a proportion of patients with covid-19 can be asymptomatic, 138 screening for symptoms might miss a larger proportion of the population with covid-19. Hence, temperature screening technologies might need to be reconsidered and evaluated for cost effectiveness, given such measures are largely depended on symptomatic fever cases.

Strengths and limitations of this review

The main strength of this systematic review was the use of a comprehensive search strategy to identify and select studies for review and thereby minimise selection bias. A clinical epidemiologist developed the search strategy, which was validated by two senior medical librarians. This review followed a comprehensive appraisal process that is recommended by the Cochrane Collaboration 31 to assess the effectiveness of public health measures, with specifically validated tools used to independently and individually assess the risk of bias in each study by study design.

This review has some limitations. Firstly, high quality evidence on SARS CoV-2 and the effectiveness of public health measures is still limited, with most studies having different underlying target variables. Secondly, information provided in this review is based on current evidence, so will be modified as additional data become available, especially from more prospective and randomised studies. Also, we excluded studies that did not provide certainty over the effect measure, which might have introduced selection bias and limited the interpretation of effectiveness. Thirdly, numerous studies measured interventions only once and others multiple times over short time frames (days v month, or no timeframe). Additionally, the meta-analytical portion of this study was limited by significant heterogeneity observed across studies, which could neither be explored nor explained by subgroup analyses or meta-regression. Finally, we quantitatively assessed only publications that reported individual measures; studies that assessed multiple measures simultaneously were narratively analysed with a broader level of effectiveness (see supplementary material 3, table 3). Also, we excluded studies in languages other than English.

Methodological limitations of studies included in the review

Several studies failed to define and assess for potential confounders, which made it difficult for our review to draw a one directional or causal conclusion. This problem was mainly because we were unable to study only one intervention, given that many countries implemented several public health measures simultaneously; thus it is a challenge to disentangle the impact of individual interventions (ie, physical distancing when other interventions could be contributing to the effect). Additionally, studies measured different primary outcomes and in varied ways, which limited the ability to statistically analyse other measures and compare effectiveness.

Further pragmatic randomised controlled trials and natural experiment studies are needed to better inform the evidence and guide the future implementation of public health measures. Given that most measures depend on a population’s adherence and compliance, it is important to understand and consider how these might be affected by factors. A lack of data in the assessed studies meant it was not possible to understand or determine the level of compliance and adherence to any of the measures.

Conclusions and policy implications

Current evidence from quantitative analyses indicates a benefit associated with handwashing, mask wearing, and physical distancing in reducing the incidence of covid-19. The narrative results of this review indicate an effectiveness of both individual or packages of public health measures on the transmission of SARS-CoV-2 and incidence of covid-19. Some of the public health measures seem to be more stringent than others and have a greater impact on economies and the health of populations. When implementing public health measures, it is important to consider specific health and sociocultural needs of the communities and to weigh the potential negative effects of the public health measures against the positive effects for general populations. Further research is needed to assess the effectiveness of public health measures after adequate vaccination coverage has been achieved. It is likely that further control of the covid-19 pandemic depends not only on high vaccination coverage and its effectiveness but also on ongoing adherence to effective and sustainable public health measures.

What is already known on this topic

Public health measures have been identified as a preventive strategy for influenza pandemics

The effectiveness of such interventions in reducing the transmission of SARS-CoV-2 is unknown

What this study adds

The findings of this review suggest that personal and social measures, including handwashing, mask wearing, and physical distancing are effective at reducing the incidence of covid-19

More stringent measures, such as lockdowns and closures of borders, schools, and workplaces need to be carefully assessed by weighing the potential negative effects of these measures on general populations

Further research is needed to assess the effectiveness of public health measures after adequate vaccination coverage

Ethics statements

Ethical approval.

Not required.

Data availability statement

No additional data available.

Acknowledgments

We thank medical subject librarians Lorena Romero (LR) and Marshall Dozier (MD) for their expert advice and assistance with the study search strategy.

Contributors: ST, DG, DI, DL, and ZA conceived and designed the study. ST, DG, SS, AM, HW, WX, JR, ET, AM, XL, XZ, and IME collected and screened the data. ST, DG, and DI acquired, analysed, or interpreted the data. ST, HW, and SS drafted the manuscript. All authors critically revised the manuscript for important intellectual content.. XL and ST did the statistical analysis. NA obtained funding. LR and MD provided administrative, technical, or material support. ST and DI supervised the study. ST and DI had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. ST is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

Funding: No funding was available for this research. ET is supported by a Cancer Research UK Career Development Fellowship (grant No C31250/A22804). XZ is supported by The Darwin Trust of Edinburgh.

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: ET is supported by a Cancer Research UK Career Development Fellowship and XZ is supported by The Darwin Trust of Edinburgh; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

The lead author (ST) affirms that the manuscript is an honest, accurate, and transparent account of the study reported; no important aspects of the study have been omitted. Dissemination to participants and related patient and public communities: It is anticipated to disseminate the results of this research to wider community via press release and social media platforms.

Provenance and peer review: Not commissioned; externally peer reviewed.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .

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• Volume 76, Issue 2
• COVID-19 pandemic and its impact on social relationships and health
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• http://orcid.org/0000-0003-1512-4471 Emily Long 1 ,
• Susan Patterson 1 ,
• Karen Maxwell 1 ,
• Carolyn Blake 1 ,
• http://orcid.org/0000-0001-7342-4566 Raquel Bosó Pérez 1 ,
• Ruth Lewis 1 ,
• Mark McCann 1 ,
• Julie Riddell 1 ,
• Kathryn Skivington 1 ,
• Rachel Wilson-Lowe 1 ,
• http://orcid.org/0000-0002-4409-6601 Kirstin R Mitchell 2
• 1 MRC/CSO Social and Public Health Sciences Unit , University of Glasgow , Glasgow , UK
• 2 MRC/CSO Social and Public Health Sciences Unit, Institute of Health & Wellbeing , University of Glasgow , Glasgow , UK
• Correspondence to Dr Emily Long, MRC/CSO Social and Public Health Sciences Unit, University of Glasgow, Glasgow G3 7HR, UK; emily.long{at}glasgow.ac.uk

This essay examines key aspects of social relationships that were disrupted by the COVID-19 pandemic. It focuses explicitly on relational mechanisms of health and brings together theory and emerging evidence on the effects of the COVID-19 pandemic to make recommendations for future public health policy and recovery. We first provide an overview of the pandemic in the UK context, outlining the nature of the public health response. We then introduce four distinct domains of social relationships: social networks, social support, social interaction and intimacy, highlighting the mechanisms through which the pandemic and associated public health response drastically altered social interactions in each domain. Throughout the essay, the lens of health inequalities, and perspective of relationships as interconnecting elements in a broader system, is used to explore the varying impact of these disruptions. The essay concludes by providing recommendations for longer term recovery ensuring that the social relational cost of COVID-19 is adequately considered in efforts to rebuild.

• inequalities

Data availability statement

Data sharing not applicable as no data sets generated and/or analysed for this study. Data sharing not applicable as no data sets generated or analysed for this essay.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/ .

https://doi.org/10.1136/jech-2021-216690

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Introduction

Infectious disease pandemics, including SARS and COVID-19, demand intrapersonal behaviour change and present highly complex challenges for public health. 1 A pandemic of an airborne infection, spread easily through social contact, assails human relationships by drastically altering the ways through which humans interact. In this essay, we draw on theories of social relationships to examine specific ways in which relational mechanisms key to health and well-being were disrupted by the COVID-19 pandemic. Relational mechanisms refer to the processes between people that lead to change in health outcomes.

At the time of writing, the future surrounding COVID-19 was uncertain. Vaccine programmes were being rolled out in countries that could afford them, but new and more contagious variants of the virus were also being discovered. The recovery journey looked long, with continued disruption to social relationships. The social cost of COVID-19 was only just beginning to emerge, but the mental health impact was already considerable, 2 3 and the inequality of the health burden stark. 4 Knowledge of the epidemiology of COVID-19 accrued rapidly, but evidence of the most effective policy responses remained uncertain.

The initial response to COVID-19 in the UK was reactive and aimed at reducing mortality, with little time to consider the social implications, including for interpersonal and community relationships. The terminology of ‘social distancing’ quickly became entrenched both in public and policy discourse. This equation of physical distance with social distance was regrettable, since only physical proximity causes viral transmission, whereas many forms of social proximity (eg, conversations while walking outdoors) are minimal risk, and are crucial to maintaining relationships supportive of health and well-being.

The aim of this essay is to explore four key relational mechanisms that were impacted by the pandemic and associated restrictions: social networks, social support, social interaction and intimacy. We use relational theories and emerging research on the effects of the COVID-19 pandemic response to make three key recommendations: one regarding public health responses; and two regarding social recovery. Our understanding of these mechanisms stems from a ‘systems’ perspective which casts social relationships as interdependent elements within a connected whole. 5

Social networks

Social networks characterise the individuals and social connections that compose a system (such as a workplace, community or society). Social relationships range from spouses and partners, to coworkers, friends and acquaintances. They vary across many dimensions, including, for example, frequency of contact and emotional closeness. Social networks can be understood both in terms of the individuals and relationships that compose the network, as well as the overall network structure (eg, how many of your friends know each other).

Social networks show a tendency towards homophily, or a phenomenon of associating with individuals who are similar to self. 6 This is particularly true for ‘core’ network ties (eg, close friends), while more distant, sometimes called ‘weak’ ties tend to show more diversity. During the height of COVID-19 restrictions, face-to-face interactions were often reduced to core network members, such as partners, family members or, potentially, live-in roommates; some ‘weak’ ties were lost, and interactions became more limited to those closest. Given that peripheral, weaker social ties provide a diversity of resources, opinions and support, 7 COVID-19 likely resulted in networks that were smaller and more homogenous.

Such changes were not inevitable nor necessarily enduring, since social networks are also adaptive and responsive to change, in that a disruption to usual ways of interacting can be replaced by new ways of engaging (eg, Zoom). Yet, important inequalities exist, wherein networks and individual relationships within networks are not equally able to adapt to such changes. For example, individuals with a large number of newly established relationships (eg, university students) may have struggled to transfer these relationships online, resulting in lost contacts and a heightened risk of social isolation. This is consistent with research suggesting that young adults were the most likely to report a worsening of relationships during COVID-19, whereas older adults were the least likely to report a change. 8

Lastly, social connections give rise to emergent properties of social systems, 9 where a community-level phenomenon develops that cannot be attributed to any one member or portion of the network. For example, local area-based networks emerged due to geographic restrictions (eg, stay-at-home orders), resulting in increases in neighbourly support and local volunteering. 10 In fact, research suggests that relationships with neighbours displayed the largest net gain in ratings of relationship quality compared with a range of relationship types (eg, partner, colleague, friend). 8 Much of this was built from spontaneous individual interactions within local communities, which together contributed to the ‘community spirit’ that many experienced. 11 COVID-19 restrictions thus impacted the personal social networks and the structure of the larger networks within the society.

Social support

Social support, referring to the psychological and material resources provided through social interaction, is a critical mechanism through which social relationships benefit health. In fact, social support has been shown to be one of the most important resilience factors in the aftermath of stressful events. 12 In the context of COVID-19, the usual ways in which individuals interact and obtain social support have been severely disrupted.

One such disruption has been to opportunities for spontaneous social interactions. For example, conversations with colleagues in a break room offer an opportunity for socialising beyond one’s core social network, and these peripheral conversations can provide a form of social support. 13 14 A chance conversation may lead to advice helpful to coping with situations or seeking formal help. Thus, the absence of these spontaneous interactions may mean the reduction of indirect support-seeking opportunities. While direct support-seeking behaviour is more effective at eliciting support, it also requires significantly more effort and may be perceived as forceful and burdensome. 15 The shift to homeworking and closure of community venues reduced the number of opportunities for these spontaneous interactions to occur, and has, second, focused them locally. Consequently, individuals whose core networks are located elsewhere, or who live in communities where spontaneous interaction is less likely, have less opportunity to benefit from spontaneous in-person supportive interactions.

However, alongside this disruption, new opportunities to interact and obtain social support have arisen. The surge in community social support during the initial lockdown mirrored that often seen in response to adverse events (eg, natural disasters 16 ). COVID-19 restrictions that confined individuals to their local area also compelled them to focus their in-person efforts locally. Commentators on the initial lockdown in the UK remarked on extraordinary acts of generosity between individuals who belonged to the same community but were unknown to each other. However, research on adverse events also tells us that such community support is not necessarily maintained in the longer term. 16

Meanwhile, online forms of social support are not bound by geography, thus enabling interactions and social support to be received from a wider network of people. Formal online social support spaces (eg, support groups) existed well before COVID-19, but have vastly increased since. While online interactions can increase perceived social support, it is unclear whether remote communication technologies provide an effective substitute from in-person interaction during periods of social distancing. 17 18 It makes intuitive sense that the usefulness of online social support will vary by the type of support offered, degree of social interaction and ‘online communication skills’ of those taking part. Youth workers, for instance, have struggled to keep vulnerable youth engaged in online youth clubs, 19 despite others finding a positive association between amount of digital technology used by individuals during lockdown and perceived social support. 20 Other research has found that more frequent face-to-face contact and phone/video contact both related to lower levels of depression during the time period of March to August 2020, but the negative effect of a lack of contact was greater for those with higher levels of usual sociability. 21 Relatedly, important inequalities in social support exist, such that individuals who occupy more socially disadvantaged positions in society (eg, low socioeconomic status, older people) tend to have less access to social support, 22 potentially exacerbated by COVID-19.

Social and interactional norms

Interactional norms are key relational mechanisms which build trust, belonging and identity within and across groups in a system. Individuals in groups and societies apply meaning by ‘approving, arranging and redefining’ symbols of interaction. 23 A handshake, for instance, is a powerful symbol of trust and equality. Depending on context, not shaking hands may symbolise a failure to extend friendship, or a failure to reach agreement. The norms governing these symbols represent shared values and identity; and mutual understanding of these symbols enables individuals to achieve orderly interactions, establish supportive relationship accountability and connect socially. 24 25

Physical distancing measures to contain the spread of COVID-19 radically altered these norms of interaction, particularly those used to convey trust, affinity, empathy and respect (eg, hugging, physical comforting). 26 As epidemic waves rose and fell, the work to negotiate these norms required intense cognitive effort; previously taken-for-granted interactions were re-examined, factoring in current restriction levels, own and (assumed) others’ vulnerability and tolerance of risk. This created awkwardness, and uncertainty, for example, around how to bring closure to an in-person interaction or convey warmth. The instability in scripted ways of interacting created particular strain for individuals who already struggled to encode and decode interactions with others (eg, those who are deaf or have autism spectrum disorder); difficulties often intensified by mask wearing. 27

Large social gatherings—for example, weddings, school assemblies, sporting events—also present key opportunities for affirming and assimilating interactional norms, building cohesion and shared identity and facilitating cooperation across social groups. 28 Online ‘equivalents’ do not easily support ‘social-bonding’ activities such as singing and dancing, and rarely enable chance/spontaneous one-on-one conversations with peripheral/weaker network ties (see the Social networks section) which can help strengthen bonds across a larger network. The loss of large gatherings to celebrate rites of passage (eg, bar mitzvah, weddings) has additional relational costs since these events are performed by and for communities to reinforce belonging, and to assist in transitioning to new phases of life. 29 The loss of interaction with diverse others via community and large group gatherings also reduces intergroup contact, which may then tend towards more prejudiced outgroup attitudes. While online interaction can go some way to mimicking these interaction norms, there are key differences. A sense of anonymity, and lack of in-person emotional cues, tends to support norms of polarisation and aggression in expressing differences of opinion online. And while online platforms have potential to provide intergroup contact, the tendency of much social media to form homogeneous ‘echo chambers’ can serve to further reduce intergroup contact. 30 31

Intimacy relates to the feeling of emotional connection and closeness with other human beings. Emotional connection, through romantic, friendship or familial relationships, fulfils a basic human need 32 and strongly benefits health, including reduced stress levels, improved mental health, lowered blood pressure and reduced risk of heart disease. 32 33 Intimacy can be fostered through familiarity, feeling understood and feeling accepted by close others. 34

Intimacy via companionship and closeness is fundamental to mental well-being. Positively, the COVID-19 pandemic has offered opportunities for individuals to (re)connect and (re)strengthen close relationships within their household via quality time together, following closure of many usual external social activities. Research suggests that the first full UK lockdown period led to a net gain in the quality of steady relationships at a population level, 35 but amplified existing inequalities in relationship quality. 35 36 For some in single-person households, the absence of a companion became more conspicuous, leading to feelings of loneliness and lower mental well-being. 37 38 Additional pandemic-related relational strain 39 40 resulted, for some, in the initiation or intensification of domestic abuse. 41 42

Physical touch is another key aspect of intimacy, a fundamental human need crucial in maintaining and developing intimacy within close relationships. 34 Restrictions on social interactions severely restricted the number and range of people with whom physical affection was possible. The reduction in opportunity to give and receive affectionate physical touch was not experienced equally. Many of those living alone found themselves completely without physical contact for extended periods. The deprivation of physical touch is evidenced to take a heavy emotional toll. 43 Even in future, once physical expressions of affection can resume, new levels of anxiety over germs may introduce hesitancy into previously fluent blending of physical and verbal intimate social connections. 44

The pandemic also led to shifts in practices and norms around sexual relationship building and maintenance, as individuals adapted and sought alternative ways of enacting sexual intimacy. This too is important, given that intimate sexual activity has known benefits for health. 45 46 Given that social restrictions hinged on reducing household mixing, possibilities for partnered sexual activity were primarily guided by living arrangements. While those in cohabiting relationships could potentially continue as before, those who were single or in non-cohabiting relationships generally had restricted opportunities to maintain their sexual relationships. Pornography consumption and digital partners were reported to increase since lockdown. 47 However, online interactions are qualitatively different from in-person interactions and do not provide the same opportunities for physical intimacy.

Recommendations and conclusions

In the sections above we have outlined the ways in which COVID-19 has impacted social relationships, showing how relational mechanisms key to health have been undermined. While some of the damage might well self-repair after the pandemic, there are opportunities inherent in deliberative efforts to build back in ways that facilitate greater resilience in social and community relationships. We conclude by making three recommendations: one regarding public health responses to the pandemic; and two regarding social recovery.

Recommendation 1: explicitly count the relational cost of public health policies to control the pandemic

Effective handling of a pandemic recognises that social, economic and health concerns are intricately interwoven. It is clear that future research and policy attention must focus on the social consequences. As described above, policies which restrict physical mixing across households carry heavy and unequal relational costs. These include for individuals (eg, loss of intimate touch), dyads (eg, loss of warmth, comfort), networks (eg, restricted access to support) and communities (eg, loss of cohesion and identity). Such costs—and their unequal impact—should not be ignored in short-term efforts to control an epidemic. Some public health responses—restrictions on international holiday travel and highly efficient test and trace systems—have relatively small relational costs and should be prioritised. At a national level, an earlier move to proportionate restrictions, and investment in effective test and trace systems, may help prevent escalation of spread to the point where a national lockdown or tight restrictions became an inevitability. Where policies with relational costs are unavoidable, close attention should be paid to the unequal relational impact for those whose personal circumstances differ from normative assumptions of two adult families. This includes consideration of whether expectations are fair (eg, for those who live alone), whether restrictions on social events are equitable across age group, religious/ethnic groupings and social class, and also to ensure that the language promoted by such policies (eg, households; families) is not exclusionary. 48 49 Forethought to unequal impacts on social relationships should thus be integral to the work of epidemic preparedness teams.

Recommendation 2: intelligently balance online and offline ways of relating

A key ingredient for well-being is ‘getting together’ in a physical sense. This is fundamental to a human need for intimate touch, physical comfort, reinforcing interactional norms and providing practical support. Emerging evidence suggests that online ways of relating cannot simply replace physical interactions. But online interaction has many benefits and for some it offers connections that did not exist previously. In particular, online platforms provide new forms of support for those unable to access offline services because of mobility issues (eg, older people) or because they are geographically isolated from their support community (eg, lesbian, gay, bisexual, transgender and queer (LGBTQ) youth). Ultimately, multiple forms of online and offline social interactions are required to meet the needs of varying groups of people (eg, LGBTQ, older people). Future research and practice should aim to establish ways of using offline and online support in complementary and even synergistic ways, rather than veering between them as social restrictions expand and contract. Intelligent balancing of online and offline ways of relating also pertains to future policies on home and flexible working. A decision to switch to wholesale or obligatory homeworking should consider the risk to relational ‘group properties’ of the workplace community and their impact on employees’ well-being, focusing in particular on unequal impacts (eg, new vs established employees). Intelligent blending of online and in-person working is required to achieve flexibility while also nurturing supportive networks at work. Intelligent balance also implies strategies to build digital literacy and minimise digital exclusion, as well as coproducing solutions with intended beneficiaries.

Recommendation 3: build stronger and sustainable localised communities

In balancing offline and online ways of interacting, there is opportunity to capitalise on the potential for more localised, coherent communities due to scaled-down travel, homeworking and local focus that will ideally continue after restrictions end. There are potential economic benefits after the pandemic, such as increased trade as home workers use local resources (eg, coffee shops), but also relational benefits from stronger relationships around the orbit of the home and neighbourhood. Experience from previous crises shows that community volunteer efforts generated early on will wane over time in the absence of deliberate work to maintain them. Adequately funded partnerships between local government, third sector and community groups are required to sustain community assets that began as a direct response to the pandemic. Such partnerships could work to secure green spaces and indoor (non-commercial) meeting spaces that promote community interaction. Green spaces in particular provide a triple benefit in encouraging physical activity and mental health, as well as facilitating social bonding. 50 In building local communities, small community networks—that allow for diversity and break down ingroup/outgroup views—may be more helpful than the concept of ‘support bubbles’, which are exclusionary and less sustainable in the longer term. Rigorously designed intervention and evaluation—taking a systems approach—will be crucial in ensuring scale-up and sustainability.

The dramatic change to social interaction necessitated by efforts to control the spread of COVID-19 created stark challenges but also opportunities. Our essay highlights opportunities for learning, both to ensure the equity and humanity of physical restrictions, and to sustain the salutogenic effects of social relationships going forward. The starting point for capitalising on this learning is recognition of the disruption to relational mechanisms as a key part of the socioeconomic and health impact of the pandemic. In recovery planning, a general rule is that what is good for decreasing health inequalities (such as expanding social protection and public services and pursuing green inclusive growth strategies) 4 will also benefit relationships and safeguard relational mechanisms for future generations. Putting this into action will require political will.

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Twitter @karenmaxSPHSU, @Mark_McCann, @Rwilsonlowe, @KMitchinGlasgow

Contributors EL and KM led on the manuscript conceptualisation, review and editing. SP, KM, CB, RBP, RL, MM, JR, KS and RW-L contributed to drafting and revising the article. All authors assisted in revising the final draft.

Funding The research reported in this publication was supported by the Medical Research Council (MC_UU_00022/1, MC_UU_00022/3) and the Chief Scientist Office (SPHSU11, SPHSU14). EL is also supported by MRC Skills Development Fellowship Award (MR/S015078/1). KS and MM are also supported by a Medical Research Council Strategic Award (MC_PC_13027).

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

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Face-to-face classes during COVID-19: a call for deliberate and well-planned school health protocols in the Philippine context

Philip joseph d sarmiento.

Christian Living Education Department, Holy Angel University, Angeles 2009, Philippines

Cora Lyn T Sarmiento

Sto. Rosario Elementary School, Department of Education-Schools Division of Angeles City, Angeles 2009, Philippines

Rina Lyn B Tolentino

Angeles Elementary School, Department of Education-Schools Division of Angeles City, Angeles 2009, Philippines

Schooling is one of the most affected aspects of human life due to coronavirus disease-2019 (COVID-19) pandemic. In a recent correspondence published, the authors reminded every country of their responsibility to come up with strategies to reopen schools safely. This paper reiterates the adherence of school health protocols as significant in the delivery of face-to-face classes following national and international guidelines in mitigating the effects of COVID-19 pandemic as a public health crisis.

Schooling is one of the most affected aspects of human life due to coronavirus disease-2019 (COVID-19) pandemic. Since the rise and threat of the pandemic, many countries around the world have decided to temporarily close schools that have affected millions of students. 1 Consequently, students who are mostly children have been facing a learning crisis due to the pandemic. 2 In a recent correspondence published in this journal, the authors cited that every country has the responsibility to come up with strategies to reopen schools in a safe manner. 3

In the Philippines, the government’s Department of Education has come up with guidelines to implement online and modular distance learning delivery of instruction. 4 This is to safeguard students from being infected by the disease. However, plans to conduct the pilot implementation of limited face-to-face delivery in low-risk areas of COVID-19 transmission for January 2021 have been approved by the president 5 but later recalled 6 due to the threat of the new strain of COVID-19. Predicaments are raised whether the country is ready to open its schools for students to go for face-to-face learning despite having been one of the longest and strictest lockdowns in the world.

School reopening for face-to-face interactions must be carefully planned to ensure the safety of students as well as teachers and school staff in a staged fashion especially in following physical distancing. 7 , 8 Planning and execution of school health protocols during this pandemic must be supported by the truthful data 9 being given by various institutions. Last 11 December 2020, the World Health Organization (WHO) has published a checklist to support school reopening and the preparation for the possible resurgence of COVID-19. 10 WHO cited that ‘The checklist is aligned with, and builds upon, existing COVID-19-related WHO guidelines and is structured around protective measures related to: 1) hand hygiene and respiratory etiquette; 2) physical distancing; 3) use of masks in schools; 4) environmental cleaning and ventilation; and 5) respecting procedures for isolation of all people with symptoms.’ 10 The checklist helps policymakers and school officials to enhance compliance and adherence to public health protocols in the time of the pandemic. 10

In conclusion, school health protocols in conducting face-to-face classes must be planned carefully following national and international guidelines to ensure that students will be safe or at least mitigate the effects of COVID-19. After all, students’ lives matter as education does to them. That is the responsibility of every government to ensure its fulfillment.

Acknowledgment

No funding was received from this paper.

Contributor Information

Philip Joseph D Sarmiento, Christian Living Education Department, Holy Angel University, Angeles 2009, Philippines.

Cora Lyn T Sarmiento, Sto. Rosario Elementary School, Department of Education-Schools Division of Angeles City, Angeles 2009, Philippines.

Rina Lyn B Tolentino, Angeles Elementary School, Department of Education-Schools Division of Angeles City, Angeles 2009, Philippines.

Conflict of interest

The authors declare no conflict of interest in this paper.

Authors’ contribution

All authors contributed to all aspects of the manuscript.

• Open access
• Published: 23 November 2020

Global strategies and effectiveness for COVID-19 prevention through contact tracing, screening, quarantine, and isolation: a systematic review

• Tadele Girum 1 ,
• Kifle Lentiro 1 ,
• Mulugeta Geremew 2 ,
• Biru Migora 2 &
• Sisay Shewamare 3  

Tropical Medicine and Health volume  48 , Article number:  91 ( 2020 ) Cite this article

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COVID-19 is an emerging disease caused by highly contagious virus called SARS-CoV-2. It caused an extensive health and economic burden around the globe. There is no proven effective treatment yet, except certain preventive mechanisms. Some studies assessing the effects of different preventive strategies have been published. However, there is no conclusive evidence. Therefore, this study aimed to review evidences related to COVID-19 prevention strategies achieved through contact tracing, screening, quarantine, and isolation to determine best practices.

We conducted a systematic review in accordance with the PRISMA and Cochrane guidelines by searching articles from major medical databases such as PubMed/Medline, Global Health Database, Embase, CINAHL, Google Scholar, and clinical trial registries. Non-randomized and modeling articles published to date in areas of COVID prevention with contact tracing, screening, quarantine, and isolation were included. Two experts screened the articles and assessed risk of bias with ROBINS-I tool and certainty of evidence with GRADE approach. The findings were presented narratively and in tabular form.

We included 22 (9 observational and 13 modeling) studies. The studies consistently reported the benefit of quarantine, contact tracing, screening, and isolation in different settings. Model estimates indicated that quarantine of exposed people averted 44 to 81% of incident cases and 31 to 63% of deaths. Quarantine along with others can also halve the reproductive number and reduce the incidence, thus, shortening the epidemic period effectively. Early initiation of quarantine, operating large-scale screenings, strong contact tracing systems, and isolation of cases can effectively reduce the epidemic. However, adhering only to screening and isolation with lower coverage can miss more than 75% of asymptomatic cases; hence, it is not effective.

Quarantine, contact tracing, screening, and isolation are effective measures of COVID-19 prevention, particularly when integrated together. In order to be more effective, quarantine should be implemented early and should cover a larger community.

Introduction

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel coronavirus was first identified in December 2019 in Wuhan China, then spread globally within weeks and resulted in an ongoing pandemic [ 1 , 2 , 3 , 4 , 5 ]. Currently, coronavirus is affecting 213 countries and territories around the world. As of 27 May 2020, more than 5.7 million cases and 353,664 deaths were reported globally [ 2 , 3 ]. Thirteen percent of the closed cohorts and 2–5% of the total cohort reportedly died [ 2 , 3 , 4 , 5 ]. The USA, Brazil, Russia, Spain, Italy, France, and the UK are the most affected countries [ 3 , 4 , 5 , 6 , 7 ].

The full spectrum of COVID-19 infection ranges from subclinical self-limiting respiratory tract illness to severe progressive pneumonia with multi-organ failure and death. As evidenced from studies and reports, more than 80% of cases remained asymptomatic and 15% of cases appeared as mild cases with common symptoms like fever, cough, fatigue, and loss of smell and taste [ 2 , 3 , 4 , 5 , 6 ]. Severe disease onset that needs intensive care might result in death due to massive alveolar damage and progressive respiratory failure [ 1 , 4 , 5 , 6 , 7 , 8 ].

The virus transmits through direct and indirect contacts. Person-to-person transmissions primarily occur during close contact, droplets produced through coughing, sneezing, and talking. Indirect transmission occurs through touching contaminated surfaces or objects and then touching the face. It is more contagious during the first few days after the onset of symptoms, but asymptomatic cases can also spread the disease [ 5 , 6 , 7 , 8 ].

Recommended prevention measures was designed based on overcoming the mode of transmissions including frequent hand washing, maintaining physical distance, quarantine, covering the mouth and nose during coughs, and avoiding contamination of face with unwashed hands. In addition, use of mask is recommended particularly for suspected individuals and their caregivers. There is limited evidence against the community wide use of masks in healthy individuals. However, most of these preventive measures are recommended and were not researched well [ 4 , 5 , 6 , 7 , 8 ].

To the extent of our search, there is no systematic review on the preventive aspects and effectiveness of COVID-19 infection through contact tracing, screening, quarantine, and isolation. The findings were inconclusive; in some studies, certain preventive mechanisms were shown to have minimal effects, while in others different preventive mechanisms have better effect than expected. On the other hand, some studies have reported that integration of interventions is more effective than specific interventions [ 2 , 6 , 8 ].

Therefore, we aimed to conduct a comprehensive systematic review through reviewing globally published studies on the strategies and effectiveness of different preventive mechanisms (contact tracing, screening, quarantine, and isolation) developed to prevent and control COVID-19. This synthesized measure will be important to bring conclusive evidence, so that policy makers and other stakeholders could have clear evidence to rely on during decision making.

To support the existing local and national COVID-19 prevention program with tangible evidence, we conducted a systematic review on global strategies for COVID-19 prevention through contact tracing, screening, quarantine, and isolation. We aimed to answer issues related to alternative strategic implementation and effectiveness in the prevention of the disease or death. The following key questions were considered:

Is contact tracing, screening, quarantine, and isolation effective to control the COVID-19 outbreak?

Is there difference in the effectiveness of contact tracing, screening, quarantine, and isolation in different settings?

How and when these strategies should be applied to control the COVID-19 outbreak?

We conducted the review in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidance for reporting of systematic reviews and meta-analyses [ 9 ] and the Cochrane Handbook of Systematic Review [ 10 ] through systematic literature search of articles published to date (June 02/2020) containing information on COVID-19 prevention by contact tracing, screening, quarantine, and isolation. First, a working protocol was developed (but unpublished) and followed in the process.

Eligibility (inclusion and exclusion) criteria for the review

Based on the relevance of the reported evidence for decision making at local, national, and international levels, the papers were selected and prioritized for the review. The relevant outcomes observed in the review were reduction in incidence, transmission, adverse outcome, and cost-effectiveness of COVID-19 prevention through contact tracing, screening, quarantine, and isolation.

Types of studies

Due to the infancy of the epidemic, lack of researches, and ethical concerns, randomized controlled trials were not included. Therefore, we considered non-randomized observational studies and modeling (mathematical and/or epidemiological) studies to supplement the existing evidences.

We included cohort studies, case-control studies, time series, case series, and mathematical modeling studies conducted anywhere, in any area, and in any setting reported in the English language. Whereas, commentaries, letter to editor, case reports, and governmental reports were excluded.

Types of participants

Depending on the type of the research, for each preventive methods, different participants were included. These includes individuals who have had contacts with confirmed or suspected case of COVID-19, or individuals who lived in areas with COVID-19 outbreak, or individuals considered to be at high risk for COVID-19/suspected cases or cases of COVID-19 infection. The number of participants varies according to the individual researches. Individuals who have confirmed other symptomatic respiratory diseases were excluded.

Types of interventions

We included different types of interventions applied specifically or in combination, either voluntary or mandatory and in different settings (facility or community). In comparative studies, the interventions were compared with the non-applied groups or other comparison groups. We excluded interventions other than the aforementioned strategies.

Types of outcome measures

To identify the extent to which these interventions were applied globally and to measure their effectiveness in COVID-19 prevention, we used the following outcome measures: incidence of COVID-19, onward transmission, mortality or other adverse outcomes, and cost-effectiveness. We did not address secondary outcomes such as psychological impacts, economic impacts, and social impacts.

Literature search strategy

A systematic literature search of articles was done by information system professionals and the researchers. Articles published between January 1, 2020, and June 2, 2020, containing information on different prevention strategies such as contact tracing, screening, quarantine, and isolation, and studies assessing their effectiveness were retained for the review. Electronic bibliographic databases and libraries such as PubMed/Medline, Global Health Database, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature; Ebsco), the Cochrane Library, and African Index Medicus were used.

In addition, we searched gray literatures, pre-prints, and resource centers of The Lancet , JAMA , and N Engl J Med . Lastly, we screened the reference lists of systematic reviews for additional source. Combination of the following search terms were used with (AND, OR, NOT) Boolean (Search) Operators.

Corona virus

Coronavirus Infections

Novel corona

Prevention/control

• Contact tracing

1 or 2 or 3 or 4 or 5 and 6 and 7 or 8 or 9 or 10

Data collection and analysis

Study selection process.

The team screened all the titles and abstracts based on predefined eligibility criteria. Two authors independently screened the titles and abstracts and reached consensus by discussion or by involving a third author. After that, the review author team retrieved the full texts of all included abstracts. Two review authors screened all the full-text publications independently, and disagreements were resolved with consensus or by a third person involvement.

Data extraction and management

Titles and abstracts found through primary electronic search were thoroughly assessed for the possibility of reporting the intended outcome and filtered for potential eligibility. One of the review authors who have experience extracted data from the included studies into standardized tables, and the second author checked completeness. From each eligible research, the following information was extracted based on the preformed format: author information, title, study participants, study design, study setting, type of intervention, length of intervention, year of publication, study duration, eligibility criteria, rate, and effect of intervention measures. For modeling studies, the data extraction items also included the type of model and the data source.

Assessment of risk of bias in included studies

Risk of bias was assessed through evaluating reliability and validity of data in included studies based on the Risk-Of-Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool [ 11 ]. The first author rated the risk of bias, the second author checked the ratings, and the third author was involved in the disagreements. For each studies, the study design, participants, outcome, and presence of bias were assessed based on the eligibility criteria and quality assessment check list. Moreover, all studies with the same participants and outcome were measured using the same standard.

On the other hand, modeling studies were assessed by the International Society for Pharmaco-economics and Outcomes (ISPOR) and the Society for Medical Decision making (SMDM) for dynamic mathematical transmission model tools [ 12 ]. Modeling studies that fulfilled all the three criteria were rated as “no concerns to minor concerns, ” and if one or more categories were unclear, it is rated as “moderate concerns,” and if one or more categories were not fulfilled, we had it rated as “major concerns.”

Data synthesis and analysis

The qualitative data was systematically reviewed and presented in accordance with the Cochrane guide line. We synthesized results from quantitative measures narratively and reported in tabular form. Because of the heterogeneity of the primary studies, quantitative analyses (meta-analysis) were not conducted.

Assessment of the certainty of the evidence

By using the GRADE approach [ 13 ], we graded the certainty of evidence for the main outcomes, reported in standard terms using tables. One of the authors conducted the certainty assessment which consists of assessments of risk of bias, indirectness, inconsistency, imprecision, and publication bias, and then, classified to one of the four categories: a high certainty (estimated effect lies close to the true effect), a moderate certainty (estimated effect is probably close to the true effect), a low certainty (estimated effect might substantially differ), and very low certainty (estimated effect is probably markedly different) from the true effect.

Studies included

The PRISMA flow diagram for the selected studies in the search process and the eligibility assessment are summarized in (Fig. 1 ). The initial electronic database search led to 1542 potentially relevant citations in the form of a title, abstract, bibliography, and full-text research. After removal of duplicates and initial screening, 125 articles were selected for further evaluation via full-text articles. Of these full-text articles, 103 articles were excluded due to the following reasons: 38 studies reported the prevention of SARS other than COVID-19; 36 have measured prevention measures other than contact tracing, screening, quarantine, and isolation; 19 had inappropriate study designs (commentaries, letters and case reports); and 10 were reviews or protocols. Thus, 22 studies [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] met the inclusion criteria and were included in the systematic review.

Flow chart for study search, selection, and screening for the review

Study characteristics

The 22 studies [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] that were retained for the final analysis were published in the period from January 15, 2020, to June 02, 2020, based on participant populations in the following countries: China ( n = 10), UK ( n = 4), USA ( n = 2), Hong Kong ( n = 2), and Netherlands, Japan, France, and Taiwan ( n = 1 from each). The included studies comprised of 9 observational [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ] and 13 modeling studies [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. With duplicates (repeated count), 3 of the studies assessed the overall prevention strategies [ 21 , 22 , 23 ], 5 assessed the effect of contact tracing [ 14 , 24 , 25 , 33 , 35 ], 2 assessed screening strategies [ 17 , 34 ], 12 assessed the effect of quarantine [ 15 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], and 6 assessed the effect of isolation [ 17 , 25 , 26 , 31 , 33 , 35 ]. The sample sizes in the studies varied from hundreds to millions. Four studies were investigated for effect at the health facility level, while the remaining 18 studies explored at the community or national level. Survey characteristics and summary results are described in Table  1 .

Quality (risk of bias) assessment within included studies

Summaries of the risk of bias assessment of non-randomized studies and quality rating of the modeling studies are presented in Tables 2 and 3 , respectively. Two studies [ 14 , 19 ] have low bias due to confounding, eight studies have low bias in selection of participants into the study, and all studies have low bias in classification of interventions. The overall risk of bias is moderate for eight studies and serious for one study. On the other hand, we have no concern for nine modeling studies, and two studies have major concerns.

COVID-19 prevention strategies and effectiveness

The summary result is presented in Table 1 . Among the nine observational studies, three of them assessed COVID-19 transmission with the existing prevention measures at a community level in Taiwan, China, and Hong Kong [ 18 , 19 , 20 ]. The other two studies assessed the effect of escalating prevention measures at health facilities in China and Hong Kong [ 21 , 22 ], and three studies [ 15 , 16 , 17 ] assessed national- and metropolitan-based quarantine strategies and the effect of laboratory-based quarantine in the prevention of COVID-19. The last study evaluated the effect of community-based contact tracing in UK [ 14 ].

The three studies [ 18 , 19 , 20 ] that assessed the overall prevention strategies found out that integration of interventions need to be applied instead of adhering to a single intervention. Cheng [ 18 ] reported that isolating symptomatic patients alone may not be sufficient enough to contain the epidemic. Wang [ 19 ] and Law [ 20 ] also concluded that in intimate contacts the transmission is 40–60%. Preventing contact through different strategies and integration is very important.

Studies conducted on the effect of quarantine [ 15 , 16 , 17 ] found that it can have a massive preventive effect. One of the studies [ 15 ] that assessed the effect of quarantine in different populations and quarantine strategies found that it should be integrated with input population reduction (travel restriction), and the other study [ 16 ] that assessed the effects of metropolitan-wide quarantine on the Spread of COVID-19 in China found that quarantine would prevent 79.27% (75.10–83.45%) of deaths and 87.08% (84.68–89.49%) of infections. Also, the other researcher [ 17 ] evidenced that laboratory-based screenings accomplished within hours can enhance the efficiency of quarantine.

Two studies described infection control preparedness measures in health care settings of Hong Kong and China [ 21 , 22 ]. One of these studies [ 21 ] reported that infection transmission is highly increased within a short period of time and multiplicity of infection prevention strategies were recommended for prevention in health care setups. The other study [ 22 ] also concluded that practicing working shift among professionals working in facilities can be used as strategy to prevent thetransmission of COVID infection.

A study conducted by Keeling et al. [ 14 ] assessed the efficacy of contact tracing for the containment of COVID-19 in the UK. The study evaluated the contact pattern of the community and concluded that rapid contact tracing to reduce the basic reproduction number ( R 0 ) from 3.11 to 0.21 enables the outbreak to be contained. Additionally, it was found that each new case requires an average of 36 individuals to be traced, with 8.7% of cases having more than 100 close traceable contacts.

In this review, we identified 13 modeling studies [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] that assessed the effectiveness of contact tracing, screening, quarantine, and isolation for prevention of COVID-19 in different settings and groups. The simulation was done in individual or group basis and with different assumptions. Most of these studies used a model parameter from Chinese reports.

Three of these researches [ 25 , 26 , 27 ] particularly emphasized on the way how the R 0 can be reduced and the epidemic would be reduced. The simulation by Tang et al. [ 25 ] aimed to estimate the R 0 of SARS-CoV-2 and infer the required effectiveness of isolation and quarantine to contain the outbreak. Their susceptible-exposed-infected-recovered (SEIR) model estimated R 0 of 6.47 and generalized that 50% reduction of contact rate achieved by isolation and quarantine would decrease the confirmed cases by 44%; reducing contacts by 90% also can decrease the number of cases by 65%. The other researcher, Rocklov (27), by using data from the Diamond Princess Cruise ship, concluded that quarantine of passengers prevented 67% of cases and lowered the R 0 from 14.8 to 1.78. Similarly, the reduction of R 0 was achieved from quarantine [ 28 ].

In addition to these, five studies [ 24 , 28 , 30 , 31 , 35 ] which modeled the effectiveness of different public interventions consistently reported that integrated intervention is better than a single intervention. One of these research conducted in the UK [ 24 ] found that combined isolation and tracing strategies would reduce transmission more than mass testing or self-isolation alone (50–60% compared to 2–30%). The other study [ 28 ] also reported that with R 0 of 2.4, a combination of case isolation and voluntary quarantine for 3 months could prevent 31% of deaths. The others also concluded that quarantine should be strict and integrated with contact tracing, screening, and other interventions [ 30 , 31 , 35 ].

Five modeling studies also assessed the effect of quarantine [ 23 , 29 , 32 ], contact tracing [ 33 ], and screening [ 34 ]. All of the studies [ 23 , 29 , 32 ] reported that quarantine has reduced the incidence of infection and shortened the duration of the epidemic. However, the effectiveness depends on the level of integration with other strategies. Similarly, model simulations that assessed the effect of contact tracing and screening reported that the strategies are effective. However, as the report of Hellewell [ 33 ] stated, contact tracing and isolation might not contain outbreaks of COVID-19 unless very high levels of contact tracing are achieved. Similarly, the other researcher [ 34 ] reported that in a stable epidemic, under the assumption that 25% of cases are subclinical, it is estimated that arrival screening alone would detect roughly one-third of infected travelers.

This study aimed to assess the effectiveness of contact tracing, screening, and quarantine and isolation to prevent COVID-19 infection by reviewing existing literatures. The review identified and systematically synthesized the findings of 22 studies (9 observational and 13 modeling studies) [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] to bring the best available evidence that policy makers and implementers can use in the process of infection prevention interventions.

The studies consistently reported the benefit of contact tracing, screening, quarantine, and isolation in the prevention of COVID-19. The effectiveness of quarantine in particular is very high. Compared to individuals without any intervention quarantined people exposed to a confirmed case highly averted infections and deaths [ 15 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Also, the effectiveness of quarantine increases whenever it is implemented along with other prevention measures such as isolation, contact tracing, and travel ban [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Although, screening and contact tracing are very important to control the epidemic, early initiation, larger coverage, and integration with other programs are very important. Unless the level of contact tracing and screening is high, prevention through isolation only is very limited, as the screening programs misses 75% of cases [ 3 , 24 ].

Quarantine measures applied alone or integrated with other measures were reported to be the most effective measures [ 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. However, integration of quarantine with other public health measures increases the effectiveness and efficiency of the program [ 36 ]. Implementation of early quarantine measures makes the strategy a more cost effective one [ 28 , 30 ]. Quarantine implemented as self-quarantine and group quarantine is effective at varying levels once effectively implemented [ 28 , 32 ]. Total lockdown measures enhance the effectiveness of quarantine measures [ 15 , 16 , 17 , 18 , 19 ]. When laboratory tests are very fast, laboratory-based quarantine could be an effective in health care setups [ 17 ].

This evidence is in line with the finding of other reviews and modeling studies conducted to assess the effectiveness of these measures in the prevention of SARS, MERS, and COVID-19 [ 28 , 35 , 36 , 37 ]. As reported before, combination of case isolation and voluntary quarantine for 3 months could prevent 31% of deaths compared to any single intervention. And adding social distancing on the previous interventions on people aged 70 years or older for 4 months increases the prevention proportion of deaths to 49%. It can also reduce the reproductive number by half; hence, it can tremendously reduce the incidence of infection, reduce the period of epidemic, and enhance effectiveness of control [ 28 , 36 ].

Our findings also witnessed the effectiveness of contact tracing measures used for pandemic response efforts at multiple levels of health care systems. Isolation of suspected and confirmed patients and their contact is at the heart of the prevention strategy. However, for the contact tracing to be an effective measure, it has to be integrated with other measures such as quarantine and screening. Because larger shares of individuals are asymptomatic, contact tracing may be difficult in areas where contact recording is unachievable. According to world health organization, contact tracing is also one of the most essential and effective strategies to control the epidemic [ 14 , 24 , 25 , 33 , 35 ]. Other studies also evidenced the importance of contact tracing and isolation in different settings [ 36 , 37 ].

The finding of our review revealed that screening and isolation are important measures of disease prevention [ 17 , 25 , 26 , 31 , 33 , 35 ]. Most of the researches recommend high-risk group screening and contact cases screening in a resource-limited setting. However, these programs are effective when the screening capacity is higher and contact tracing is effective. Otherwise, screening and isolation programs miss more than half of cases and may not be implemented alone [ 25 , 33 , 35 ]. Also evidences from different countries indicated that screening and isolation measures are implemented along with other measures, yet their role in the prevention of the epidemic is high [ 2 , 3 , 8 , 36 , 37 ].

This review included a wide variety of study designs (observational and model studies); hence, it failed to include meta-analysis (statistical measures). Modeled studies also assume different scenarios, where it may not be true in the general cases. Also, the review has included only publications reported in the English language and open access resources.

Conclusion and recommendation

Quarantine, contact tracing, screening, and isolation are effective measures of COVID-19 prevention, particularly whenever integrated together. In order to be more effective, quarantine should be implemented early and covers larger community. Controlling population travel will enhance the effectiveness of quarantine. Screening, contact tracing, and isolation are effective particularly in areas where contact tracing is easily attainable. Although screening is the effective measure recommended by the WHO, since the disease is asymptomatic, it may miss a larger share of the population. Therefore, this should be integrated with other preventive measures. In order to control the COVID-19 epidemic, the health care system should consider high level of contact tracing, early initiation of nationwide quarantine measures, increasing coverage of screening service, and preparing effective isolation centers.

Availability of data and materials

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Abbreviations

Coronavirus disease 2019

Middle East respiratory syndrome

Severe acute respiratory syndrome

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Basic reproduction number

Susceptible-exposed-infected-recovered

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Girum, T., Lentiro, K., Geremew, M. et al. Global strategies and effectiveness for COVID-19 prevention through contact tracing, screening, quarantine, and isolation: a systematic review. Trop Med Health 48 , 91 (2020). https://doi.org/10.1186/s41182-020-00285-w

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Navigating the rapidly growing body of scientific literature on the SARS-CoV-2 pandemic is challenging, and ongoing critical appraisal of this output is essential. We aimed to summarize and critically appraise systematic reviews of coronavirus disease (COVID-19) in humans that were available at the beginning of the pandemic.

Nine databases (Medline, EMBASE, Cochrane Library, CINAHL, Web of Sciences, PDQ-Evidence, WHO’s Global Research, LILACS, and Epistemonikos) were searched from December 1, 2019, to March 24, 2020. Systematic reviews analyzing primary studies of COVID-19 were included. Two authors independently undertook screening, selection, extraction (data on clinical symptoms, prevalence, pharmacological and non-pharmacological interventions, diagnostic test assessment, laboratory, and radiological findings), and quality assessment (AMSTAR 2). A meta-analysis was performed of the prevalence of clinical outcomes.

Eighteen systematic reviews were included; one was empty (did not identify any relevant study). Using AMSTAR 2, confidence in the results of all 18 reviews was rated as “critically low”. Identified symptoms of COVID-19 were (range values of point estimates): fever (82–95%), cough with or without sputum (58–72%), dyspnea (26–59%), myalgia or muscle fatigue (29–51%), sore throat (10–13%), headache (8–12%) and gastrointestinal complaints (5–9%). Severe symptoms were more common in men. Elevated C-reactive protein and lactate dehydrogenase, and slightly elevated aspartate and alanine aminotransferase, were commonly described. Thrombocytopenia and elevated levels of procalcitonin and cardiac troponin I were associated with severe disease. A frequent finding on chest imaging was uni- or bilateral multilobar ground-glass opacity. A single review investigated the impact of medication (chloroquine) but found no verifiable clinical data. All-cause mortality ranged from 0.3 to 13.9%.

Conclusions

In this overview of systematic reviews, we analyzed evidence from the first 18 systematic reviews that were published after the emergence of COVID-19. However, confidence in the results of all reviews was “critically low”. Thus, systematic reviews that were published early on in the pandemic were of questionable usefulness. Even during public health emergencies, studies and systematic reviews should adhere to established methodological standards.

Peer Review reports

The spread of the “Severe Acute Respiratory Coronavirus 2” (SARS-CoV-2), the causal agent of COVID-19, was characterized as a pandemic by the World Health Organization (WHO) in March 2020 and has triggered an international public health emergency [ 1 ]. The numbers of confirmed cases and deaths due to COVID-19 are rapidly escalating, counting in millions [ 2 ], causing massive economic strain, and escalating healthcare and public health expenses [ 3 , 4 ].

The research community has responded by publishing an impressive number of scientific reports related to COVID-19. The world was alerted to the new disease at the beginning of 2020 [ 1 ], and by mid-March 2020, more than 2000 articles had been published on COVID-19 in scholarly journals, with 25% of them containing original data [ 5 ]. The living map of COVID-19 evidence, curated by the Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre), contained more than 40,000 records by February 2021 [ 6 ]. More than 100,000 records on PubMed were labeled as “SARS-CoV-2 literature, sequence, and clinical content” by February 2021 [ 7 ].

Due to publication speed, the research community has voiced concerns regarding the quality and reproducibility of evidence produced during the COVID-19 pandemic, warning of the potential damaging approach of “publish first, retract later” [ 8 ]. It appears that these concerns are not unfounded, as it has been reported that COVID-19 articles were overrepresented in the pool of retracted articles in 2020 [ 9 ]. These concerns about inadequate evidence are of major importance because they can lead to poor clinical practice and inappropriate policies [ 10 ].

Systematic reviews are a cornerstone of today’s evidence-informed decision-making. By synthesizing all relevant evidence regarding a particular topic, systematic reviews reflect the current scientific knowledge. Systematic reviews are considered to be at the highest level in the hierarchy of evidence and should be used to make informed decisions. However, with high numbers of systematic reviews of different scope and methodological quality being published, overviews of multiple systematic reviews that assess their methodological quality are essential [ 11 , 12 , 13 ]. An overview of systematic reviews helps identify and organize the literature and highlights areas of priority in decision-making.

In this overview of systematic reviews, we aimed to summarize and critically appraise systematic reviews of coronavirus disease (COVID-19) in humans that were available at the beginning of the pandemic.

Methodology

Research question.

This overview’s primary objective was to summarize and critically appraise systematic reviews that assessed any type of primary clinical data from patients infected with SARS-CoV-2. Our research question was purposefully broad because we wanted to analyze as many systematic reviews as possible that were available early following the COVID-19 outbreak.

Study design

We conducted an overview of systematic reviews. The idea for this overview originated in a protocol for a systematic review submitted to PROSPERO (CRD42020170623), which indicated a plan to conduct an overview.

Overviews of systematic reviews use explicit and systematic methods for searching and identifying multiple systematic reviews addressing related research questions in the same field to extract and analyze evidence across important outcomes. Overviews of systematic reviews are in principle similar to systematic reviews of interventions, but the unit of analysis is a systematic review [ 14 , 15 , 16 ].

We used the overview methodology instead of other evidence synthesis methods to allow us to collate and appraise multiple systematic reviews on this topic, and to extract and analyze their results across relevant topics [ 17 ]. The overview and meta-analysis of systematic reviews allowed us to investigate the methodological quality of included studies, summarize results, and identify specific areas of available or limited evidence, thereby strengthening the current understanding of this novel disease and guiding future research [ 13 ].

A reporting guideline for overviews of reviews is currently under development, i.e., Preferred Reporting Items for Overviews of Reviews (PRIOR) [ 18 ]. As the PRIOR checklist is still not published, this study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 statement [ 19 ]. The methodology used in this review was adapted from the Cochrane Handbook for Systematic Reviews of Interventions and also followed established methodological considerations for analyzing existing systematic reviews [ 14 ].

Approval of a research ethics committee was not necessary as the study analyzed only publicly available articles.

Eligibility criteria

Systematic reviews were included if they analyzed primary data from patients infected with SARS-CoV-2 as confirmed by RT-PCR or another pre-specified diagnostic technique. Eligible reviews covered all topics related to COVID-19 including, but not limited to, those that reported clinical symptoms, diagnostic methods, therapeutic interventions, laboratory findings, or radiological results. Both full manuscripts and abbreviated versions, such as letters, were eligible.

No restrictions were imposed on the design of the primary studies included within the systematic reviews, the last search date, whether the review included meta-analyses or language. Reviews related to SARS-CoV-2 and other coronaviruses were eligible, but from those reviews, we analyzed only data related to SARS-CoV-2.

No consensus definition exists for a systematic review [ 20 ], and debates continue about the defining characteristics of a systematic review [ 21 ]. Cochrane’s guidance for overviews of reviews recommends setting pre-established criteria for making decisions around inclusion [ 14 ]. That is supported by a recent scoping review about guidance for overviews of systematic reviews [ 22 ].

Thus, for this study, we defined a systematic review as a research report which searched for primary research studies on a specific topic using an explicit search strategy, had a detailed description of the methods with explicit inclusion criteria provided, and provided a summary of the included studies either in narrative or quantitative format (such as a meta-analysis). Cochrane and non-Cochrane systematic reviews were considered eligible for inclusion, with or without meta-analysis, and regardless of the study design, language restriction and methodology of the included primary studies. To be eligible for inclusion, reviews had to be clearly analyzing data related to SARS-CoV-2 (associated or not with other viruses). We excluded narrative reviews without those characteristics as these are less likely to be replicable and are more prone to bias.

Scoping reviews and rapid reviews were eligible for inclusion in this overview if they met our pre-defined inclusion criteria noted above. We included reviews that addressed SARS-CoV-2 and other coronaviruses if they reported separate data regarding SARS-CoV-2.

Information sources

Nine databases were searched for eligible records published between December 1, 2019, and March 24, 2020: Cochrane Database of Systematic Reviews via Cochrane Library, PubMed, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Sciences, LILACS (Latin American and Caribbean Health Sciences Literature), PDQ-Evidence, WHO’s Global Research on Coronavirus Disease (COVID-19), and Epistemonikos.

The comprehensive search strategy for each database is provided in Additional file 1 and was designed and conducted in collaboration with an information specialist. All retrieved records were primarily processed in EndNote, where duplicates were removed, and records were then imported into the Covidence platform [ 23 ]. In addition to database searches, we screened reference lists of reviews included after screening records retrieved via databases.

Study selection

All searches, screening of titles and abstracts, and record selection, were performed independently by two investigators using the Covidence platform [ 23 ]. Articles deemed potentially eligible were retrieved for full-text screening carried out independently by two investigators. Discrepancies at all stages were resolved by consensus. During the screening, records published in languages other than English were translated by a native/fluent speaker.

Data collection process

We custom designed a data extraction table for this study, which was piloted by two authors independently. Data extraction was performed independently by two authors. Conflicts were resolved by consensus or by consulting a third researcher.

We extracted the following data: article identification data (authors’ name and journal of publication), search period, number of databases searched, population or settings considered, main results and outcomes observed, and number of participants. From Web of Science (Clarivate Analytics, Philadelphia, PA, USA), we extracted journal rank (quartile) and Journal Impact Factor (JIF).

We categorized the following as primary outcomes: all-cause mortality, need for and length of mechanical ventilation, length of hospitalization (in days), admission to intensive care unit (yes/no), and length of stay in the intensive care unit.

The following outcomes were categorized as exploratory: diagnostic methods used for detection of the virus, male to female ratio, clinical symptoms, pharmacological and non-pharmacological interventions, laboratory findings (full blood count, liver enzymes, C-reactive protein, d-dimer, albumin, lipid profile, serum electrolytes, blood vitamin levels, glucose levels, and any other important biomarkers), and radiological findings (using radiography, computed tomography, magnetic resonance imaging or ultrasound).

We also collected data on reporting guidelines and requirements for the publication of systematic reviews and meta-analyses from journal websites where included reviews were published.

Quality assessment in individual reviews

Two researchers independently assessed the reviews’ quality using the “A MeaSurement Tool to Assess Systematic Reviews 2 (AMSTAR 2)”. We acknowledge that the AMSTAR 2 was created as “a critical appraisal tool for systematic reviews that include randomized or non-randomized studies of healthcare interventions, or both” [ 24 ]. However, since AMSTAR 2 was designed for systematic reviews of intervention trials, and we included additional types of systematic reviews, we adjusted some AMSTAR 2 ratings and reported these in Additional file 2 .

Adherence to each item was rated as follows: yes, partial yes, no, or not applicable (such as when a meta-analysis was not conducted). The overall confidence in the results of the review is rated as “critically low”, “low”, “moderate” or “high”, according to the AMSTAR 2 guidance based on seven critical domains, which are items 2, 4, 7, 9, 11, 13, 15 as defined by AMSTAR 2 authors [ 24 ]. We reported our adherence ratings for transparency of our decision with accompanying explanations, for each item, in each included review.

One of the included systematic reviews was conducted by some members of this author team [ 25 ]. This review was initially assessed independently by two authors who were not co-authors of that review to prevent the risk of bias in assessing this study.

Synthesis of results

For data synthesis, we prepared a table summarizing each systematic review. Graphs illustrating the mortality rate and clinical symptoms were created. We then prepared a narrative summary of the methods, findings, study strengths, and limitations.

For analysis of the prevalence of clinical outcomes, we extracted data on the number of events and the total number of patients to perform proportional meta-analysis using RStudio© software, with the “meta” package (version 4.9–6), using the “metaprop” function for reviews that did not perform a meta-analysis, excluding case studies because of the absence of variance. For reviews that did not perform a meta-analysis, we presented pooled results of proportions with their respective confidence intervals (95%) by the inverse variance method with a random-effects model, using the DerSimonian-Laird estimator for τ 2 . We adjusted data using Freeman-Tukey double arcosen transformation. Confidence intervals were calculated using the Clopper-Pearson method for individual studies. We created forest plots using the RStudio© software, with the “metafor” package (version 2.1–0) and “forest” function.

Managing overlapping systematic reviews

Some of the included systematic reviews that address the same or similar research questions may include the same primary studies in overviews. Including such overlapping reviews may introduce bias when outcome data from the same primary study are included in the analyses of an overview multiple times. Thus, in summaries of evidence, multiple-counting of the same outcome data will give data from some primary studies too much influence [ 14 ]. In this overview, we did not exclude overlapping systematic reviews because, according to Cochrane’s guidance, it may be appropriate to include all relevant reviews’ results if the purpose of the overview is to present and describe the current body of evidence on a topic [ 14 ]. To avoid any bias in summary estimates associated with overlapping reviews, we generated forest plots showing data from individual systematic reviews, but the results were not pooled because some primary studies were included in multiple reviews.

Our search retrieved 1063 publications, of which 175 were duplicates. Most publications were excluded after the title and abstract analysis ( n = 860). Among the 28 studies selected for full-text screening, 10 were excluded for the reasons described in Additional file 3 , and 18 were included in the final analysis (Fig. 1 ) [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Reference list screening did not retrieve any additional systematic reviews.

PRISMA flow diagram

Characteristics of included reviews

Summary features of 18 systematic reviews are presented in Table 1 . They were published in 14 different journals. Only four of these journals had specific requirements for systematic reviews (with or without meta-analysis): European Journal of Internal Medicine, Journal of Clinical Medicine, Ultrasound in Obstetrics and Gynecology, and Clinical Research in Cardiology . Two journals reported that they published only invited reviews ( Journal of Medical Virology and Clinica Chimica Acta ). Three systematic reviews in our study were published as letters; one was labeled as a scoping review and another as a rapid review (Table 2 ).

All reviews were published in English, in first quartile (Q1) journals, with JIF ranging from 1.692 to 6.062. One review was empty, meaning that its search did not identify any relevant studies; i.e., no primary studies were included [ 36 ]. The remaining 17 reviews included 269 unique studies; the majority ( N = 211; 78%) were included in only a single review included in our study (range: 1 to 12). Primary studies included in the reviews were published between December 2019 and March 18, 2020, and comprised case reports, case series, cohorts, and other observational studies. We found only one review that included randomized clinical trials [ 38 ]. In the included reviews, systematic literature searches were performed from 2019 (entire year) up to March 9, 2020. Ten systematic reviews included meta-analyses. The list of primary studies found in the included systematic reviews is shown in Additional file 4 , as well as the number of reviews in which each primary study was included.

Population and study designs

Most of the reviews analyzed data from patients with COVID-19 who developed pneumonia, acute respiratory distress syndrome (ARDS), or any other correlated complication. One review aimed to evaluate the effectiveness of using surgical masks on preventing transmission of the virus [ 36 ], one review was focused on pediatric patients [ 34 ], and one review investigated COVID-19 in pregnant women [ 37 ]. Most reviews assessed clinical symptoms, laboratory findings, or radiological results.

Systematic review findings

The summary of findings from individual reviews is shown in Table 2 . Overall, all-cause mortality ranged from 0.3 to 13.9% (Fig. 2 ).

A meta-analysis of the prevalence of mortality

Clinical symptoms

Seven reviews described the main clinical manifestations of COVID-19 [ 26 , 28 , 29 , 34 , 35 , 39 , 41 ]. Three of them provided only a narrative discussion of symptoms [ 26 , 34 , 35 ]. In the reviews that performed a statistical analysis of the incidence of different clinical symptoms, symptoms in patients with COVID-19 were (range values of point estimates): fever (82–95%), cough with or without sputum (58–72%), dyspnea (26–59%), myalgia or muscle fatigue (29–51%), sore throat (10–13%), headache (8–12%), gastrointestinal disorders, such as diarrhea, nausea or vomiting (5.0–9.0%), and others (including, in one study only: dizziness 12.1%) (Figs. 3 , 4 , 5 , 6 , 7 , 8 and 9 ). Three reviews assessed cough with and without sputum together; only one review assessed sputum production itself (28.5%).

A meta-analysis of the prevalence of fever

A meta-analysis of the prevalence of cough

A meta-analysis of the prevalence of dyspnea

A meta-analysis of the prevalence of fatigue or myalgia

A meta-analysis of the prevalence of headache

A meta-analysis of the prevalence of gastrointestinal disorders

A meta-analysis of the prevalence of sore throat

Diagnostic aspects

Three reviews described methodologies, protocols, and tools used for establishing the diagnosis of COVID-19 [ 26 , 34 , 38 ]. The use of respiratory swabs (nasal or pharyngeal) or blood specimens to assess the presence of SARS-CoV-2 nucleic acid using RT-PCR assays was the most commonly used diagnostic method mentioned in the included studies. These diagnostic tests have been widely used, but their precise sensitivity and specificity remain unknown. One review included a Chinese study with clinical diagnosis with no confirmation of SARS-CoV-2 infection (patients were diagnosed with COVID-19 if they presented with at least two symptoms suggestive of COVID-19, together with laboratory and chest radiography abnormalities) [ 34 ].

Therapeutic possibilities

Pharmacological and non-pharmacological interventions (supportive therapies) used in treating patients with COVID-19 were reported in five reviews [ 25 , 27 , 34 , 35 , 38 ]. Antivirals used empirically for COVID-19 treatment were reported in seven reviews [ 25 , 27 , 34 , 35 , 37 , 38 , 41 ]; most commonly used were protease inhibitors (lopinavir, ritonavir, darunavir), nucleoside reverse transcriptase inhibitor (tenofovir), nucleotide analogs (remdesivir, galidesivir, ganciclovir), and neuraminidase inhibitors (oseltamivir). Umifenovir, a membrane fusion inhibitor, was investigated in two studies [ 25 , 35 ]. Possible supportive interventions analyzed were different types of oxygen supplementation and breathing support (invasive or non-invasive ventilation) [ 25 ]. The use of antibiotics, both empirically and to treat secondary pneumonia, was reported in six studies [ 25 , 26 , 27 , 34 , 35 , 38 ]. One review specifically assessed evidence on the efficacy and safety of the anti-malaria drug chloroquine [ 27 ]. It identified 23 ongoing trials investigating the potential of chloroquine as a therapeutic option for COVID-19, but no verifiable clinical outcomes data. The use of mesenchymal stem cells, antifungals, and glucocorticoids were described in four reviews [ 25 , 34 , 35 , 38 ].

Laboratory and radiological findings

Of the 18 reviews included in this overview, eight analyzed laboratory parameters in patients with COVID-19 [ 25 , 29 , 30 , 32 , 33 , 34 , 35 , 39 ]; elevated C-reactive protein levels, associated with lymphocytopenia, elevated lactate dehydrogenase, as well as slightly elevated aspartate and alanine aminotransferase (AST, ALT) were commonly described in those eight reviews. Lippi et al. assessed cardiac troponin I (cTnI) [ 25 ], procalcitonin [ 32 ], and platelet count [ 33 ] in COVID-19 patients. Elevated levels of procalcitonin [ 32 ] and cTnI [ 30 ] were more likely to be associated with a severe disease course (requiring intensive care unit admission and intubation). Furthermore, thrombocytopenia was frequently observed in patients with complicated COVID-19 infections [ 33 ].

Chest imaging (chest radiography and/or computed tomography) features were assessed in six reviews, all of which described a frequent pattern of local or bilateral multilobar ground-glass opacity [ 25 , 34 , 35 , 39 , 40 , 41 ]. Those six reviews showed that septal thickening, bronchiectasis, pleural and cardiac effusions, halo signs, and pneumothorax were observed in patients suffering from COVID-19.

Quality of evidence in individual systematic reviews

Table 3 shows the detailed results of the quality assessment of 18 systematic reviews, including the assessment of individual items and summary assessment. A detailed explanation for each decision in each review is available in Additional file 5 .

Using AMSTAR 2 criteria, confidence in the results of all 18 reviews was rated as “critically low” (Table 3 ). Common methodological drawbacks were: omission of prospective protocol submission or publication; use of inappropriate search strategy: lack of independent and dual literature screening and data-extraction (or methodology unclear); absence of an explanation for heterogeneity among the studies included; lack of reasons for study exclusion (or rationale unclear).

Risk of bias assessment, based on a reported methodological tool, and quality of evidence appraisal, in line with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method, were reported only in one review [ 25 ]. Five reviews presented a table summarizing bias, using various risk of bias tools [ 25 , 29 , 39 , 40 , 41 ]. One review analyzed “study quality” [ 37 ]. One review mentioned the risk of bias assessment in the methodology but did not provide any related analysis [ 28 ].

This overview of systematic reviews analyzed the first 18 systematic reviews published after the onset of the COVID-19 pandemic, up to March 24, 2020, with primary studies involving more than 60,000 patients. Using AMSTAR-2, we judged that our confidence in all those reviews was “critically low”. Ten reviews included meta-analyses. The reviews presented data on clinical manifestations, laboratory and radiological findings, and interventions. We found no systematic reviews on the utility of diagnostic tests.

Symptoms were reported in seven reviews; most of the patients had a fever, cough, dyspnea, myalgia or muscle fatigue, and gastrointestinal disorders such as diarrhea, nausea, or vomiting. Olfactory dysfunction (anosmia or dysosmia) has been described in patients infected with COVID-19 [ 43 ]; however, this was not reported in any of the reviews included in this overview. During the SARS outbreak in 2002, there were reports of impairment of the sense of smell associated with the disease [ 44 , 45 ].

The reported mortality rates ranged from 0.3 to 14% in the included reviews. Mortality estimates are influenced by the transmissibility rate (basic reproduction number), availability of diagnostic tools, notification policies, asymptomatic presentations of the disease, resources for disease prevention and control, and treatment facilities; variability in the mortality rate fits the pattern of emerging infectious diseases [ 46 ]. Furthermore, the reported cases did not consider asymptomatic cases, mild cases where individuals have not sought medical treatment, and the fact that many countries had limited access to diagnostic tests or have implemented testing policies later than the others. Considering the lack of reviews assessing diagnostic testing (sensitivity, specificity, and predictive values of RT-PCT or immunoglobulin tests), and the preponderance of studies that assessed only symptomatic individuals, considerable imprecision around the calculated mortality rates existed in the early stage of the COVID-19 pandemic.

Few reviews included treatment data. Those reviews described studies considered to be at a very low level of evidence: usually small, retrospective studies with very heterogeneous populations. Seven reviews analyzed laboratory parameters; those reviews could have been useful for clinicians who attend patients suspected of COVID-19 in emergency services worldwide, such as assessing which patients need to be reassessed more frequently.

All systematic reviews scored poorly on the AMSTAR 2 critical appraisal tool for systematic reviews. Most of the original studies included in the reviews were case series and case reports, impacting the quality of evidence. Such evidence has major implications for clinical practice and the use of these reviews in evidence-based practice and policy. Clinicians, patients, and policymakers can only have the highest confidence in systematic review findings if high-quality systematic review methodologies are employed. The urgent need for information during a pandemic does not justify poor quality reporting.

We acknowledge that there are numerous challenges associated with analyzing COVID-19 data during a pandemic [ 47 ]. High-quality evidence syntheses are needed for decision-making, but each type of evidence syntheses is associated with its inherent challenges.

The creation of classic systematic reviews requires considerable time and effort; with massive research output, they quickly become outdated, and preparing updated versions also requires considerable time. A recent study showed that updates of non-Cochrane systematic reviews are published a median of 5 years after the publication of the previous version [ 48 ].

Authors may register a review and then abandon it [ 49 ], but the existence of a public record that is not updated may lead other authors to believe that the review is still ongoing. A quarter of Cochrane review protocols remains unpublished as completed systematic reviews 8 years after protocol publication [ 50 ].

Rapid reviews can be used to summarize the evidence, but they involve methodological sacrifices and simplifications to produce information promptly, with inconsistent methodological approaches [ 51 ]. However, rapid reviews are justified in times of public health emergencies, and even Cochrane has resorted to publishing rapid reviews in response to the COVID-19 crisis [ 52 ]. Rapid reviews were eligible for inclusion in this overview, but only one of the 18 reviews included in this study was labeled as a rapid review.

Ideally, COVID-19 evidence would be continually summarized in a series of high-quality living systematic reviews, types of evidence synthesis defined as “ a systematic review which is continually updated, incorporating relevant new evidence as it becomes available ” [ 53 ]. However, conducting living systematic reviews requires considerable resources, calling into question the sustainability of such evidence synthesis over long periods [ 54 ].

Research reports about COVID-19 will contribute to research waste if they are poorly designed, poorly reported, or simply not necessary. In principle, systematic reviews should help reduce research waste as they usually provide recommendations for further research that is needed or may advise that sufficient evidence exists on a particular topic [ 55 ]. However, systematic reviews can also contribute to growing research waste when they are not needed, or poorly conducted and reported. Our present study clearly shows that most of the systematic reviews that were published early on in the COVID-19 pandemic could be categorized as research waste, as our confidence in their results is critically low.

Our study has some limitations. One is that for AMSTAR 2 assessment we relied on information available in publications; we did not attempt to contact study authors for clarifications or additional data. In three reviews, the methodological quality appraisal was challenging because they were published as letters, or labeled as rapid communications. As a result, various details about their review process were not included, leading to AMSTAR 2 questions being answered as “not reported”, resulting in low confidence scores. Full manuscripts might have provided additional information that could have led to higher confidence in the results. In other words, low scores could reflect incomplete reporting, not necessarily low-quality review methods. To make their review available more rapidly and more concisely, the authors may have omitted methodological details. A general issue during a crisis is that speed and completeness must be balanced. However, maintaining high standards requires proper resourcing and commitment to ensure that the users of systematic reviews can have high confidence in the results.

Furthermore, we used adjusted AMSTAR 2 scoring, as the tool was designed for critical appraisal of reviews of interventions. Some reviews may have received lower scores than actually warranted in spite of these adjustments.

Another limitation of our study may be the inclusion of multiple overlapping reviews, as some included reviews included the same primary studies. According to the Cochrane Handbook, including overlapping reviews may be appropriate when the review’s aim is “ to present and describe the current body of systematic review evidence on a topic ” [ 12 ], which was our aim. To avoid bias with summarizing evidence from overlapping reviews, we presented the forest plots without summary estimates. The forest plots serve to inform readers about the effect sizes for outcomes that were reported in each review.

Several authors from this study have contributed to one of the reviews identified [ 25 ]. To reduce the risk of any bias, two authors who did not co-author the review in question initially assessed its quality and limitations.

Finally, we note that the systematic reviews included in our overview may have had issues that our analysis did not identify because we did not analyze their primary studies to verify the accuracy of the data and information they presented. We give two examples to substantiate this possibility. Lovato et al. wrote a commentary on the review of Sun et al. [ 41 ], in which they criticized the authors’ conclusion that sore throat is rare in COVID-19 patients [ 56 ]. Lovato et al. highlighted that multiple studies included in Sun et al. did not accurately describe participants’ clinical presentations, warning that only three studies clearly reported data on sore throat [ 56 ].

In another example, Leung [ 57 ] warned about the review of Li, L.Q. et al. [ 29 ]: “ it is possible that this statistic was computed using overlapped samples, therefore some patients were double counted ”. Li et al. responded to Leung that it is uncertain whether the data overlapped, as they used data from published articles and did not have access to the original data; they also reported that they requested original data and that they plan to re-do their analyses once they receive them; they also urged readers to treat the data with caution [ 58 ]. This points to the evolving nature of evidence during a crisis.

Our study’s strength is that this overview adds to the current knowledge by providing a comprehensive summary of all the evidence synthesis about COVID-19 available early after the onset of the pandemic. This overview followed strict methodological criteria, including a comprehensive and sensitive search strategy and a standard tool for methodological appraisal of systematic reviews.

In conclusion, in this overview of systematic reviews, we analyzed evidence from the first 18 systematic reviews that were published after the emergence of COVID-19. However, confidence in the results of all the reviews was “critically low”. Thus, systematic reviews that were published early on in the pandemic could be categorized as research waste. Even during public health emergencies, studies and systematic reviews should adhere to established methodological standards to provide patients, clinicians, and decision-makers trustworthy evidence.

Availability of data and materials

All data collected and analyzed within this study are available from the corresponding author on reasonable request.

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Acknowledgments

We thank Catherine Henderson DPhil from Swanscoe Communications for pro bono medical writing and editing support. We acknowledge support from the Covidence Team, specifically Anneliese Arno. We thank the whole International Network of Coronavirus Disease 2019 (InterNetCOVID-19) for their commitment and involvement. Members of the InterNetCOVID-19 are listed in Additional file 6 . We thank Pavel Cerny and Roger Crosthwaite for guiding the team supervisor (IJBN) on human resources management.

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Israel Júnior Borges do Nascimento & Milena Soriano Marcolino

Medical College of Wisconsin, Milwaukee, WI, USA

Israel Júnior Borges do Nascimento

Helene Fuld Health Trust National Institute for Evidence-based Practice in Nursing and Healthcare, College of Nursing, The Ohio State University, Columbus, OH, USA

Dónal P. O’Mathúna

School of Nursing, Psychotherapy and Community Health, Dublin City University, Dublin, Ireland

Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany

Thilo Caspar von Groote

Department of Sport and Health Science, Technische Universität München, Munich, Germany

Hebatullah Mohamed Abdulazeem

School of Health Sciences, Faculty of Health and Medicine, The University of Newcastle, Callaghan, Australia

Ishanka Weerasekara

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Livia Puljak

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IJBN conceived the research idea and worked as a project coordinator. DPOM, TCVG, HMA, IW, AM, LP, VTC, IZG, TPP, ANA, SF, NLB and MSM were involved in data curation, formal analysis, investigation, methodology, and initial draft writing. All authors revised the manuscript critically for the content. The author(s) read and approved the final manuscript.

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Supplementary Information

Additional file 1: appendix 1..

Search strategies used in the study.

Additional file 2: Appendix 2.

Adjusted scoring of AMSTAR 2 used in this study for systematic reviews of studies that did not analyze interventions.

Additional file 3: Appendix 3.

List of excluded studies, with reasons.

Additional file 4: Appendix 4.

Table of overlapping studies, containing the list of primary studies included, their visual overlap in individual systematic reviews, and the number in how many reviews each primary study was included.

Additional file 5: Appendix 5.

A detailed explanation of AMSTAR scoring for each item in each review.

Additional file 6: Appendix 6.

List of members and affiliates of International Network of Coronavirus Disease 2019 (InterNetCOVID-19).

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Borges do Nascimento, I.J., O’Mathúna, D.P., von Groote, T.C. et al. Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews. BMC Infect Dis 21 , 525 (2021). https://doi.org/10.1186/s12879-021-06214-4

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Understanding COVID-19

How To Protect Yourself During the Pandemic

COVID-19 has claimed millions of lives around the world. But we learn more about this disease every day. Scientists are developing tools that promise to slow and eventu­ally help us overcome the pandemic.

COVID-19 is caused by a new coronavirus called SARS-CoV-2. There are many types of coronaviruses. Some cause the common cold. Others have led to fatal disease outbreaks. These include severe acute respiratory syndrome (SARS) in 2003, Middle East respiratory syndrome (MERS) in 2012, and now COVID-19.

Coronaviruses are named for the crown-like spikes on their surface. (Corona means crown.) The viruses use the spikes to help get inside your body’s cells. Once inside, they replicate, or make copies of themselves.

Scientists have learned how to turn these spikes against the virus through vaccines and treatments. They’ve also learned what you can do to protect yourself from the virus.

Protecting Yourself

You’re most likely to get COVID-19 through close contact with someone who’s infected. Coughing, sneezing, talking, and breathing produce small droplets of liquid. These are called respiratory droplets. They travel through the air and can be inhaled by someone else.

“COVID-19 is spread mainly through exposure to respiratory droplets that tend to drop within six feet,” says Dr. Anthony Fauci, director of NIH’s National Institute of Allergy and Infectious Diseases. That’s why it’s important to stay at least six feet (about two arm lengths) away from people who don’t live with you.

“Surfaces can be contaminated. But it is likely that this is a less common cause of infection rather than person-to-person directly,” Fauci says.

You can protect yourself and others by wearing a mask. Choose one that has at least two layers of fabric. Make sure that the mask covers your mouth and nose and doesn’t leak air around the edges.

“There’s very little transmission in places where masks are worn,” says Dr. Ben Cowling at the University of Hong Kong who studies how viruses spread. Cowling found that infections were most often spread in settings where masks aren’t worn.

“Masks work. But even with mandatory masking, you still need social distancing as well,” he says. You can lower your risk by avoiding crowds. Crowds increase the risk of coming in contact with someone who has COVID-19.

What to Look For

Common symptoms of COVID-19 include fever, cough, headaches, fatigue, and muscle or body aches. People with COVID-19 may also lose their sense of smell or taste. Symptoms usually appear two to 14 days after being exposed to the virus.

But even people who don’t seem sick can still infect others. The CDC estimates that 50% of infections are spread by people with no symptoms. While some with this virus develop life-threatening illness, others have mild symptoms, and some never develop any.

Catching the virus is more dangerous for some groups of people. This includes older adults and people with certain medical conditions. These medical conditions include obesity, diabetes, heart and lung disease, and asthma. About 40% of Americans have at least one of these risk factors.

Getting Treatment

Better COVID-19 treatments mean that fewer people now get severely sick if they catch the virus. Scientists have been working to test available drugs against the virus. They’ve found at least two that can help people who are hospitalized with the virus.

A drug called remdesivir can reduce the time a patient spends in the hospital. A steroid called dexamethasone helps stop the immune system The system that protects your body from invading viruses, bacteria, and other microscopic threats. from reacting too strongly to the virus. That can damage body tissues and organs.

Antibody treatments are also available. Antibodies are proteins that your body makes to fight germs. Scientists have learned how to make them in the lab. Antibody treatments can block SARS-CoV-2 to prevent the illness from getting worse. They seem to have the most benefit when given early in the disease.

“Antibody treatments really do have the potential to help people, especially for treating individuals who are not yet hospitalized,” says Dr. Mark Heise, who studies the genetics of viruses at the University of North Carolina at Chapel Hill. Heise is working to develop mouse models to test treatments and vaccines.

Studies are now testing combinations of treatments. “Combining drugs that target both the virus and the person’s immune response may help treat COVID-19,” says Heise. Scientists are also looking for new drugs that better target the virus.

A Shot of Hope: Vaccines

It used to take a decade or more to develop a new vaccine. In this pandemic, scientists created COVID-19 vaccines in less than a year.

The first two vaccines approved for emergency use are from Moderna and Pfizer/BioNTech. Moderna’s vaccine was co-developed with NIH scientists. Both are a new type of vaccine called mRNA vaccines. mRNA carries the genetic information for your body to make proteins.

The vaccines direct the body’s cells to make a piece of the virus called the spike protein. These proteins can’t cause illness by themselves. But they teach your immune system to make antibodies against the protein. If you encounter the virus later, the antibodies provide protection against it.

The mRNA vaccines now available were shown to be more than 90% effective in large clinical trials. They can cause side effects—such as fatigue, muscle aches, joint pain, and headache. But both vaccines were found to be safe in the clinical trials.

“Get vaccinated. The vaccines are safe. They’re incredibly effective,” says Dr. Jason McLellan, an expert on coronaviruses at the University of Texas at Austin. McLellan’s research was critical in developing these vaccines. His team, along with NIH scientists, figured out how to lock the shape of the spike protein to make the most effective antibodies.

As the pandemic has gone on, new versions of the virus, or variants, have appeared. “We’re all very confident that vaccines will continue to work well against these variants,” McLellan says. “Vaccination also helps stop the development of new variants, because it provides fewer opportunities for the virus to change as it replicates.”

Many people will need to be vaccinated for the pandemic to end. Fauci estimates that 70% to 85% of the U.S. population will need to be vaccinated to get “herd immunity.” That’s the point where enough people are immune to the virus to prevent its spread. That’s important because it protects vulnerable people who can’t get vaccinated.

“It is my hope that all Americans will protect themselves by getting vaccinated when the vaccine becomes available to them,” Fauci says. “That is how our country will begin to heal and move forward.”

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MINI REVIEW article

Covid-19: emergence, spread, possible treatments, and global burden.

• 1 Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India
• 2 Department of Health Sciences, School of Education and Health, Cape Breton University, Sydney, NS, Canada

The Coronavirus (CoV) is a large family of viruses known to cause illnesses ranging from the common cold to acute respiratory tract infection. The severity of the infection may be visible as pneumonia, acute respiratory syndrome, and even death. Until the outbreak of SARS, this group of viruses was greatly overlooked. However, since the SARS and MERS outbreaks, these viruses have been studied in greater detail, propelling the vaccine research. On December 31, 2019, mysterious cases of pneumonia were detected in the city of Wuhan in China's Hubei Province. On January 7, 2020, the causative agent was identified as a new coronavirus (2019-nCoV), and the disease was later named as COVID-19 by the WHO. The virus spread extensively in the Wuhan region of China and has gained entry to over 210 countries and territories. Though experts suspected that the virus is transmitted from animals to humans, there are mixed reports on the origin of the virus. There are no treatment options available for the virus as such, limited to the use of anti-HIV drugs and/or other antivirals such as Remdesivir and Galidesivir. For the containment of the virus, it is recommended to quarantine the infected and to follow good hygiene practices. The virus has had a significant socio-economic impact globally. Economically, China is likely to experience a greater setback than other countries from the pandemic due to added trade war pressure, which have been discussed in this paper.

Introduction

Coronaviridae is a family of viruses with a positive-sense RNA that possess an outer viral coat. When looked at with the help of an electron microscope, there appears to be a unique corona around it. This family of viruses mainly cause respiratory diseases in humans, in the forms of common cold or pneumonia as well as respiratory infections. These viruses can infect animals as well ( 1 , 2 ). Up until the year 2003, coronavirus (CoV) had attracted limited interest from researchers. However, after the SARS (severe acute respiratory syndrome) outbreak caused by the SARS-CoV, the coronavirus was looked at with renewed interest ( 3 , 4 ). This also happened to be the first epidemic of the 21st century originating in the Guangdong province of China. Almost 10 years later, there was a MERS (Middle East respiratory syndrome) outbreak in 2012, which was caused by the MERS-CoV ( 5 , 6 ). Both SARS and MERS have a zoonotic origin and originated from bats. A unique feature of these viruses is the ability to mutate rapidly and adapt to a new host. The zoonotic origin of these viruses allows them to jump from host to host. Coronaviruses are known to use the angiotensin-converting enzyme-2 (ACE-2) receptor or the dipeptidyl peptidase IV (DPP-4) protein to gain entry into cells for replication ( 7 – 10 ).

In December 2019, almost seven years after the MERS 2012 outbreak, a novel Coronavirus (2019-nCoV) surfaced in Wuhan in the Hubei region of China. The outbreak rapidly grew and spread to neighboring countries. However, rapid communication of information and the increasing scale of events led to quick quarantine and screening of travelers, thus containing the spread of the infection. The major part of the infection was restricted to China, and a second cluster was found on a cruise ship called the Diamond Princess docked in Japan ( 11 , 12 ).

The new virus was identified to be a novel Coronavirus and was thus initially named 2019-nCoV; later, it was renamed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ( 13 ), and the disease it causes is now referred to as Coronavirus Disease-2019 (COVID-19) by the WHO. The virus was suspected to have begun its spread in the Huanan seafood wholesale market in the Wuhan region. It is possible that an animal that was carrying the virus was brought into or sold in the market, causing the spread of the virus in the crowded marketplace. One of the first claims made was in an article published in the Journal of Medical Virology ( 14 ), which identified snakes as the possible host. A second possibility was that pangolins could be the wild host of SARS-CoV-2 ( 15 ), though the most likely possibility is that the virus originated from bats ( 13 , 16 – 19 ). Increasing evidence and experts are now collectively concluding the virus had a natural origin in bats, as with previous such respiratory viruses ( 2 , 20 – 24 ).

Similarly, SARS and MERS were also suspected to originate from bats. In the case of MERS, the dromedary camel is an intermediate host ( 5 , 10 ). Bats have been known to harbor coronaviruses for quite some time now. Just as in the case of avian flu, SARS, MERS, and possibly even HIV, with increasing selection and ecological pressure due to human activities, the virus made the jump from animal to man. Humans have been encroaching increasingly into forests, and this is true over much of China, as in Africa. Combined with additional ecological pressure due to climate change, such zoonotic spillovers are now more common than ever. It is likely that the next disease X will also have such an origin ( 25 ). We have learned the importance of identification of the source organism due to the Ebola virus pandemic. Viruses are unstable organisms genetically, constantly mutating by genetic shift or drift. It is not possible to predict when a cross-species jump may occur and when a seemingly harmless variant form of the virus may turn into a deadly strain. Such an incident occurred in Reston, USA, with the Reston virus ( 26 ), an alarming reminder of this possibility. The identification of the original host helps us to contain future spreads as well as to learn about the mechanism of transmission of viruses. Until the virus is isolated from a wild animal host, in this case, mostly bats, the zoonotic origin will remain hypothetical, though likely. It should further be noted that the virus has acquired several mutations, as noted by a group in China, indicating that there are more than two strains of the virus, which may have had an impact on its pathogenicity. However, this claim remains unproven, and many experts have argued otherwise; data proving this are not yet available ( 27 ). A similar finding was reported from Italy and India independently, where they found two strains ( 28 , 29 ). These findings need to be further cross-verified by similar analyses globally. If true, this finding could effectively explain why some nations are more affected than others.

Transmission

When the spread of COVID-19 began ( Figure 1 ), the virus appeared to be contained within China and the cruise ship “Diamond Princess,” which formed the major clusters of the virus. However, as of April 2020, over 210 countries and territories are affected by the virus, with Europe, the USA, and Iran forming the new cluster of the virus. The USA ( Figure 2 ) has the highest number of confirmed COVID-19 cases, whereas India and China, despite being among the most population-dense countries in the world, have managed to constrain the infection rate by the implementation of a complete lockdown with arrangements in place to manage the confirmed cases. Similarly, the UK has also managed to maintain a low curve of the graph by implementing similar measures, though it was not strictly enforced. Reports have indicated that the presence of different strains or strands of the virus may have had an effect on the management of the infection rate of the virus ( 27 – 29 ). The disease is spread by droplet transmission. As of April 2020, the total number of infected individuals stands at around 3 million, with ~200,000 deaths and more than 1 million recoveries globally ( 30 , 34 ). The virus thus has a fatality rate of around 2% and an R 0 of 3 based on current data. However, a more recent report from the CDC, Atlanta, USA, claims that the R 0 could be as high as 5.7 ( 35 ). It has also been observed from data available from China and India that individuals likely to be infected by the virus from both these countries belong to the age groups of 20–50 years ( 36 , 37 ). In both of these countries, the working class mostly belongs to this age group, making exposure more likely. Germany and Singapore are great examples of countries with a high number of cases but low fatalities as compared to their immediate neighbors. Singapore is one of the few countries that had developed a detailed plan of action after the previous SARS outbreak to deal with a similar situation in the future, and this worked in their favor during this outbreak. Both countries took swift action after the outbreak began, with Singapore banning Chinese travelers and implementing screening and quarantine measures at a time when the WHO recommended none. They ordered the elderly and the vulnerable to strictly stay at home, and they ensured that lifesaving equipment and large-scale testing facilities were available immediately ( 38 , 39 ). Germany took similar measures by ramping up testing capacity quite early and by ensuring that all individuals had equal opportunity to get tested. This meant that young, old, and at-risk people all got tested, thus ensuring positive results early during disease progression and that most cases were mild like in Singapore, thus maintaining a lower death percentage ( 40 ). It allowed infected individuals to be identified and quarantined before they even had symptoms. Testing was carried out at multiple labs, reducing the load and providing massive scale, something which countries such as the USA did quite late and India restricted to select government and private labs. The German government also banned large gatherings and advocated social distancing to further reduce the spread, though unlike India and the USA, this was done quite late. South Korea is another example of how a nation has managed to contain the spread and transmission of the infection. South Korea and the USA both reported their first COVID-19 cases on the same day; however, the US administration downplayed the risks of the disease, unlike South Korean officials, who constantly informed their citizens about the developments of the disease using the media and a centralized messaging system. They also employed the Trace, Test, and Treat protocol to identify and isolate patients fast, whereas the USA restricted this to patients with severe infection and only later broadened this criterion, like many European countries as well as India. Unlike the USA, South Korea also has universal healthcare, ensuring free diagnostic testing.

Figure 1 . Timeline of COVID-19 progression ( 30 – 32 ).

Figure 2 . Total confirmed COVID 19 cases as of May 2020 ( 33 ).

The main mode of transmission of 2019-nCoV is human to human. As of now, animal-to-human transfer has not yet been confirmed. Asymptomatic carriers of the virus are at major risk of being superinfectors with this disease, as all those infected may not develop the disease ( 41 ). This is a concern that has been raised by nations globally, with the Indian government raising concerns on how to identify and contain asymptomatic carriers, who could account for 80% of those infected ( 42 ). Since current resources are directed towards understanding the hospitalized individuals showing symptoms, there is still a vast amount of information about asymptomatic individuals that has yet to be studied. For example, some questions that need to be answered include: Do asymptomatic individuals develop the disease at any point in time at all? Do they eventually develop antibodies? How long do they shed the virus for? Can any tissue of these individuals store the virus in a dormant state? Asymptomatic transmission is a gray area that encompasses major unknowns in COVID-19.

The main route of human-to-human transmission is by droplets, which are generated during coughing, talking, or sneezing and are then inhaled by a healthy individual. They can also be indirectly transmitted to a person when they land on surfaces that are touched by a healthy individual who may then touch their nose, mouth, or eyes, allowing the virus entry into the body. Fomites are also a common issue in such diseases ( 43 ).

Aerosol-based transmission of the virus has not yet been confirmed ( 43 ). Stool-based transmission via the fecal-oral route may also be possible since the SARS-CoV-2 has been found in patient feces ( 44 , 45 ). Some patients with COVID-19 tend to develop diarrhea, which can become a major route of transmission if proper sanitation and personal hygiene needs are not met. There is no evidence currently available to suggest intrauterine vertical transmission of the disease in pregnant women ( 46 ).

More investigation is necessary of whether climate has played any role in the containment of the infection in countries such as India, Singapore, China, and Israel, as these are significantly warmer countries as compared with the UK, the USA, and Canada ( Figure 2 ). Ideally, a warm climate should prevent the virus from surviving for longer periods of time on surfaces, reducing transmissibility.

Pathophysiology

On gaining entry via any of the mucus membranes, the single-stranded RNA-based virus enters the host cell using type 2 transmembrane serine protease (TMPRSS2) and ACE2 receptor protein, leading to fusion and endocytosis with the host cell ( 47 – 49 ). The uncoated RNA is then translated, and viral proteins are synthesized. With the help of RNA-dependant RNA polymerase, new RNA is produced for the new virions. The cell then undergoes lysis, releasing a load of new virions into the patients' body. The resultant infection causes a massive release of pro-inflammatory cytokines that causes a cytokine storm.

Clinical Presentation

The clinical presentation of the disease resembles beta coronavirus infections. The virus has an incubation time of 2–14 days, which is the reason why most patients suspected to have the illness or contact with an individual having the illness remain in quarantine for the said amount of time. Infection with SARS-CoV-2 causes severe pneumonia, intermittent fever, and cough ( 50 , 51 ). Symptoms of rhinorrhoea, pharyngitis, and sneezing have been less commonly seen. Patients often develop acute respiratory distress syndrome within 2 days of hospital admission, requiring ventilatory support. It has been observed that during this phase, the mortality tends to be high. Chest CT will show indicators of pneumonia and ground-glass opacity, a feature that has helped to improve the preliminary diagnosis ( 51 ). The primary method of diagnosis for SARS-CoV-2 is with the help of PCR. For the PCR testing, the US CDC recommends testing for the N gene, whereas the Chinese CDC recommends the use of ORF lab and N gene of the viral genome for testing. Some also rely on the radiological findings for preliminary screening ( 52 ). Additionally, immunodiagnostic tests based on the presence of antibodies can also play a role in testing. While the WHO recommends the use of these tests for research use, many countries have pre-emptively deployed the use of these tests in the hope of ramping up the rate and speed of testing ( 52 – 54 ). Later, they noticed variations among the results, causing them to stop the use of such kits; there was also debate among the experts about the sensitivity and specificity of the tests. For immunological tests, it is beneficial to test for antibodies against the virus produced by the body rather than to test for the presence of the viral proteins, since the antibodies can be present in larger titers for a longer span of time. However, the cross-reactivity of these tests with other coronavirus antibodies is something that needs verification. Biochemical parameters such as D-dimer, C-reactive protein, and variations in neutrophil and lymphocyte counts are some other parameters that can be used to make a preliminary diagnosis; however, these parameters vary in a number of diseases and thus cannot be relied upon conclusively ( 51 ). Patients with pre-existing diseases such as asthma or similar lung disorder are at higher risk, requiring life support, as are those with other diseases such as diabetes, hypertension, or obesity. Those above the age of 60 have displayed the highest mortality rate in China, a finding that is mirrored in other nations as well ( Figure 3 ) ( 55 ). If we cross-verify these findings with the population share that is above the age of 70, we find that Italy, the United Kingdom, Canada, and the USA have one of the highest elderly populations as compared to countries such as India and China ( Figure 4 ), and this also reflects the case fatality rates accordingly ( Figure 5 ) ( 33 ). This is a clear indicator that aside from comorbidities, age is also an independent risk factor for death in those infected by COVID-19. Also, in the US, it was seen that the rates of African American deaths were higher. This is probably due to the fact that the prevalence of hypertension and obesity in this community is higher than in Caucasians ( 56 , 57 ). In late April 2020, there are also claims in the US media that young patients in the US with COVID-19 may be at increased risk of stroke; however, this is yet to be proven. We know that coagulopathy is a feature of COVID-19, and thus stroke is likely in this condition ( 58 , 59 ). The main cause of death in COVID-19 patients was acute respiratory distress due to the inflammation in the linings of the lungs caused by the cytokine storm, which is seen in all non-survival cases and in respiratory failure. The resultant inflammation in the lungs, served as an entry point of further infection, associated with coagulopathy end-organ failure, septic shock, and secondary infections leading to death ( 60 – 63 ).

Figure 3 . Case fatality rate by age in selected countries as of April 2020 ( 33 ).

Figure 4 . Case fatality rate in selected countries ( 33 ).

Figure 5 . Population share above 70 years of age ( 33 ).

For COVID-19, there is no specific treatment available. The WHO announced the organization of a trial dubbed the “Solidarity” clinical trial for COVID-19 treatments ( 64 ). This is an international collaborative study that investigates the use of a few prime candidate drugs for use against COVID-19, which are discussed below. The study is designed to reduce the time taken for an RCT by over 80%. There are over 1087 studies ( Supplementary Data 1 ) for COVID-19 registered at clinicaltrials.gov , of which 657 are interventional studies ( Supplementary Data 2 ) ( 65 ). The primary focus of the interventional studies for COVID-19 has been on antimalarial drugs and antiviral agents ( Table 1 ), while over 200 studies deal with the use of different forms of oxygen therapy. Most trials focus on improvement of clinical status, reduction of viral load, time to improvement, and reduction of mortality rates. These studies cover both severe and mild cases.

Table 1 . List of therapeutic drugs under study for COVID-19 as per clinical trials registered under clinicaltrials.gov .

Use of Antimalarial Drugs Against SARS-CoV-2

The use of chloroquine for the treatment of corona virus-based infection has shown some benefit in the prevention of viral replication in the cases of SARS and MERS. However, it was not validated on a large scale in the form of a randomized control trial ( 50 , 66 – 68 ). The drugs of choice among antimalarials are Chloroquine (CQ) and Hydroxychloroquine (HCQ). The use of CQ for COVID-19 was brought to light by the Chinese, especially by the publication of a letter to the editor of Bioscience Trends by Gao et al. ( 69 ). The letter claimed that several studies found CQ to be effective against COVID-19; however, the letter did not provide many details. Immediately, over a short span of time, interest in these two agents grew globally. Early in vitro data have revealed that chloroquine can inhibit the viral replication ( 70 , 71 ).

HCQ and CQ work by raising the pH of the lysosome, the cellular organelle that is responsible for phagocytic degradation. Its function is to combine with cell contents that have been phagocytosed and break them down eventually, in some immune cells, as a downstream process to display some of the broken proteins as antigens, thus further enhancing the immune recruitment against an antigen/pathogen. The drug was to be administered alone or with azithromycin. The use of azithromycin may be advocated by the fact that it has been seen previously to have some immunomodulatory role in airway-related disease. It appears to reduce the release of pro-inflammatory cytokines in respiratory illnesses ( 72 ). However, HCQ and azithromycin are known to have a major drug interaction when co-administered, which increases the risk of QT interval prolongation ( 73 ). Quinine-based drugs are known to have adverse effects such as QT prolongation, retinal damage, hypoglycemia, and hemolysis of blood in patients with G-6-PD deficiency ( 66 ). Several preprints, including, a metanalysis now indicate that HCQ may have no benefit for severe or critically ill patients who have COVID-19 where the outcome is need for ventilation or death ( 74 , 75 ). As of April 21, 2020, after having pre-emptively recommended their use for SARS-CoV-2 infection, the US now advocates against the use of these two drugs based on the new data that has become available.

Use of Antiviral Drugs Against SARS-CoV-2

The antiviral agents are mainly those used in the case of HIV/AIDS, these being Lopinavir and Ritonavir. Other agents such as nucleoside analogs like Favipiravir, Ribavirin, Remdesivir, and Galidesivir have been tested for possible activity in the prevention of viral RNA synthesis ( 76 ). Among these drugs, Lopinavir, Ritonavir, and Remdesivir are listed in the Solidarity trial by the WHO.

Remdesivir is a nucleotide analog for adenosine that gets incorporated into the viral RNA, hindering its replication and causing chain termination. This agent was originally developed for Ebola Virus Disease ( 77 ). A study was conducted with rhesus macaques infected with SARS-CoV-2 ( 78 ). In that study, after 12 h of infection, the monkeys were treated with either Remdesivir or vehicle. The drug showed good distribution in the lungs, and the animals treated with the drug showed a better clinical score than the vehicle group. The radiological findings of the study also indicated that the animals treated with Remdesivir have less lung damage. There was a reduction in viral replication but not in virus shedding. Furthermore, there were no mutations found in the RNA polymerase sequences. A randomized clinical control study that became available in late April 2020 ( 79 ), having 158 on the Remdesivir arm and 79 on the placebo arm, found that Remdesivir reduced the time to recovery in the Remdesivir-treated arm to 11 days, while the placebo-arm recovery time was 15 days. Though this was not found to be statistically significant, the agent provided a basis for further studies. The 28-days mortality was found to be similar for both groups. This has now provided us with a basis on which to develop future molecules. The study has been supported by the National Institute of Health, USA. The authors of the study advocated for more clinical trials with Remdesivir with a larger population. Such larger studies are already in progress, and their results are awaited. Remdesivir is currently one of the drugs that hold most promise against COVID-19.

An early trial in China with Lopinavir and Ritonavir showed no benefit compared with standard clinical care ( 80 ). More studies with this drug are currently underway, including one in India ( 81 , 82 ).

Use of Convalescent Patient Plasma

Another possible option would be the use of serum from convalescent individuals, as this is known to contain antibodies that can neutralize the virus and aid in its elimination. This has been tried previously for other coronavirus infections ( 83 ). Early emerging case reports in this aspect look promising compared to other therapies that have been tried ( 84 – 87 ). A report from China indicates that five patients treated with plasma recovered and were eventually weaned off ventilators ( 84 ). They exhibited reductions in fever and viral load and improved oxygenation. The virus was not detected in the patients after 12 days of plasma transfusion. The US FDA has provided detailed recommendations for investigational COVID-19 Convalescent Plasma use ( 88 ). One of the benefits of this approach is that it can also be used for post-exposure prophylaxis. This approach is now beginning to be increasingly adopted in other countries, with over 95 trials registered on clinicaltrials.gov alone, of which at least 75 are interventional ( 89 ). The use of convalescent patient plasma, though mostly for research purposes, appears to be the best and, so far, the only successful option for treatment available.

From a future perspective, the use of monoclonal antibodies for the inhibition of the attachment of the virus to the ACE-2 receptor may be the best bet. Aside from this, ACE-2-like molecules could also be utilized to attach and inactivate the viral proteins, since inhibition of the ACE-2 receptor would not be advisable due to its negative repercussions physiologically. In the absence of drug regimens and a vaccine, the treatment is symptomatic and involves the use of non-invasive ventilation or intubation where necessary for respiratory failure patients. Patients that may go into septic shock should be managed as per existing guidelines with hemodynamic support as well as antibiotics where necessary.

The WHO has recommended that simple personal hygiene practices can be sufficient for the prevention of spread and containment of the disease ( 90 ). Practices such as frequent washing of soiled hands or the use of sanitizer for unsoiled hands help reduce transmission. Covering of mouth while sneezing and coughing, and disinfection of surfaces that are frequently touched, such as tabletops, doorknobs, and switches with 70% isopropyl alcohol or other disinfectants are broadly recommended. It is recommended that all individuals afflicted by the disease, as well as those caring for the infected, wear a mask to avoid transmission. Healthcare works are advised to wear a complete set of personal protective equipment as per WHO-provided guidelines. Fumigation of dormitories, quarantine rooms, and washing of clothes and other fomites with detergent and warm water can help get rid of the virus. Parcels and goods are not known to transmit the virus, as per information provided by the WHO, since the virus is not able to survive sufficiently in an open, exposed environment. Quarantine of infected individuals and those who have come into contact with an infected individual is necessary to further prevent transmission of the virus ( 91 ). Quarantine is an age-old archaic practice that continues to hold relevance even today for disease containment. With the quarantine being implemented on such a large scale in some countries, taking the form of a national lockdown, the question arises of its impact on the mental health of all individuals. This topic needs to be addressed, especially in countries such as India and China, where it is still a matter of partial taboo to talk about it openly within the society.

In India, the Ministry of Ayurveda, Yoga, and Naturopathy, Unani, Siddha and Homeopathy (AYUSH), which deals with the alternative forms of medicine, issued a press release that the homeopathic, drug Arsenicum album 30, can be taken on an empty stomach for 3 days to provide protection against the infection ( 92 ). It also provided a list of herbal drugs in the same press release as per Ayurvedic and Unani systems of medicine that can boost the immune system to deal with the virus. However, there is currently no evidence to support the use of these systems of medicine against COVID-19, and they need to be tested.

The prevention of the disease with the use of a vaccine would provide a more viable solution. There are no vaccines available for any of the coronaviruses, which includes SARS and MERS. The development of a vaccine, however, is in progress at a rapid pace, though it could take about a year or two. As of April 2020, no vaccine has completed the development and testing process. A popular approach has been with the use of mRNA-based vaccine ( 93 – 96 ). mRNA vaccines have the advantage over conventional vaccines in terms of production, since they can be manufactured easily and do not have to be cultured, as a virus would need to be. Alternative conventional approaches to making a vaccine against SARS-CoV-2 would include the use of live attenuated virus as well as using the isolated spike proteins of the virus. Both of these approaches are in progress for vaccine development ( 97 ). Governments across the world have poured in resources and made changes in their legislation to ensure rapid development, testing, and deployment of a vaccine.

Barriers to Treatment

Lack of transparency and poor media relations.

The lack of government transparency and poor reporting by the media have hampered the measures that could have been taken by healthcare systems globally to deal with the COVID-19 threat. The CDC, as well as the US administration, downplayed the threat and thus failed to stock up on essential supplies, ventilators, and test kits. An early warning system, if implemented, would have caused borders to be shut and early lockdowns. The WHO also delayed its response in sounding the alarm regarding the severity of the outbreak to allow nations globally to prepare for a pandemic. Singapore is a prime example where, despite the WHO not raising concerns and banning travel to and from China, a country banned travelers and took early measures, thus managing the outbreak quite well. South Korea is another example of how things may have played out had those measures by agencies been taken with transparency. Increased transparency would have allowed the healthcare sector to better prepare and reduced the load of patients they had to deal with, helping flatten the curve. The increased patient load and confusion among citizens arising from not following these practices has proved to be a barrier to providing effective treatments to patients with the disease elsewhere in the world.

Lack of Preparedness and Protocols

Despite the previous SARS outbreak teaching us important lessons and providing us with data on a potential outbreak, many nations did not take the important measures needed for a future outbreak. There was no allocation of sufficient funds for such an event. Many countries experienced severe lack of PPE, and the lockdown precautions hampered the logistics of supply and manufacturing of such essential equipment. Singapore and South Korea had protocols in place and were able to implement them at a moment's notice. The spurt of cases that Korea experienced was managed well, providing evidence to this effect. The lack of preparedness and lack of protocol in other nations has resulted in confusion as to how the treatment may be administered safely to the large volume of patients while dealing with diagnostics. Both of these factors have limited the accessibility to healthcare services due to sheer volume.

Socio-Economic Impact

During the SARS epidemic, China faced an economic setback, and experts were unsure if any recovery would be made. However, the global and domestic situation was then in China's favor, as it had a lower debt, allowing it to make a speedy recovery. This is not the case now. Global experts have a pessimistic outlook on the outcome of this outbreak ( 98 ). The fear of COVID-19 disease, lack of proper understanding of the dangers of the virus, and the misinformation spread on the social media ( 99 ) have caused a breakdown of the economic flow globally ( 100 ). An example of this is Indonesia, where a great amount of fear was expressed in responses to a survey when the nation was still free of COVID-19 ( 101 ). The pandemic has resulted in over 2.6 billion people being put under lockdown. This lockdown and the cancellation of the lunar year celebration has affected business at the local level. Hundreds of flights have been canceled, and tourism globally has been affected. Japan and Indonesia are estimated to lose over 2.44 billion dollars due to this ( 102 , 103 ). Workers are not able to work in factories, transportation in all forms is restricted, and goods are not produced or moved. The transport of finished products and raw materials out of China is low. The Economist has published US stock market details indicating that companies in the US that have Chinese roots fell, on average, 5 points on the stock market as compared to the S&P 500 index ( 104 ). Companies such as Starbucks have had to close over 4,000 outlets due to the outbreak as a precaution. Tech and pharma companies are at higher risk since they rely on China for the supply of raw materials and active pharmaceutical ingredients. Paracetamol, for one, has reported a price increase of over 40% in India ( 104 – 106 ). Mass hysteria in the market has caused selling of shares of these companies, causing a tumble in the Indian stock market. Though long-term investors will not be significantly affected, short-term traders will find themselves in soup. Politically, however, this has further bolstered support for world leaders in countries such as India, Germany, and the UK, who are achieving good approval ratings, with citizens being satisfied with the government's approach. In contrast, the ratings of US President Donald Trump have dropped due to the manner in which the COVID-19 pandemic was handled. These minor impacts may be of temporary significance, and the worst and direct impact will be on China itself ( 107 – 109 ), as the looming trade war with the USA had a negative impact on the Chinese and Asian markets. The longer production of goods continues to remain suspended, the more adversely it will affect the Chinese economy and the global markets dependent on it ( 110 ). If this disease is not contained, more and more lockdowns by multiple nations will severely affect the economy and lead to many social complications.

The appearance of the 2019 Novel Coronavirus has added and will continue to add to our understanding of viruses. The pandemic has once again tested the world's preparedness for dealing with such outbreaks. It has provided an outlook on how a massive-scale biological event can cause a socio-economic disturbance through misinformation and social media. In the coming months and years, we can expect to gain further insights into SARS-CoV-2 and COVID-19.

Author Contributions

KN: conceptualization. RK, AA, JM, and KN: investigation. RK and AA: writing—original draft preparation. KN, PN, and JM: writing—review and editing. KN: supervision.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

The authors would like to acknowledge the contributions made by Dr. Piya Paul Mudgal, Assistant Professor, Manipal Institute of Virology, Manipal Academy of Higher Education towards inputs provided by her during the drafting of the manuscript.

Supplementary Material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpubh.2020.00216/full#supplementary-material

Supplementary Data 1, 2. List of all studies registered for COVID-19 on clinicaltrials.gov .

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Keywords: 2019-nCoV, COVID-19, SARS-CoV-2, coronavirus, pandemic, SARS

Citation: Keni R, Alexander A, Nayak PG, Mudgal J and Nandakumar K (2020) COVID-19: Emergence, Spread, Possible Treatments, and Global Burden. Front. Public Health 8:216. doi: 10.3389/fpubh.2020.00216

Received: 21 February 2020; Accepted: 11 May 2020; Published: 28 May 2020.

Reviewed by:

Copyright © 2020 Keni, Alexander, Nayak, Mudgal and Nandakumar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Krishnadas Nandakumar, mailnandakumar77@gmail.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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• Published: 11 February 2021

Methodological quality of COVID-19 clinical research

• Richard G. Jung   ORCID: orcid.org/0000-0002-8570-6736 1 , 2 , 3   na1 ,
• Pietro Di Santo 1 , 2 , 4 , 5   na1 ,
• Cole Clifford 6 ,
• Graeme Prosperi-Porta 7 ,
• Stephanie Skanes 6 ,
• Annie Hung 8 ,
• Simon Parlow 4 ,
• Sarah Visintini   ORCID: orcid.org/0000-0001-6966-1753 9 ,
• F. Daniel Ramirez   ORCID: orcid.org/0000-0002-4350-1652 1 , 4 , 10 , 11 ,
• Trevor Simard 1 , 2 , 3 , 4 , 12 &
• Benjamin Hibbert   ORCID: orcid.org/0000-0003-0906-1363 2 , 3 , 4  

Nature Communications volume  12 , Article number:  943 ( 2021 ) Cite this article

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The COVID-19 pandemic began in early 2020 with major health consequences. While a need to disseminate information to the medical community and general public was paramount, concerns have been raised regarding the scientific rigor in published reports. We performed a systematic review to evaluate the methodological quality of currently available COVID-19 studies compared to historical controls. A total of 9895 titles and abstracts were screened and 686 COVID-19 articles were included in the final analysis. Comparative analysis of COVID-19 to historical articles reveals a shorter time to acceptance (13.0[IQR, 5.0–25.0] days vs. 110.0[IQR, 71.0–156.0] days in COVID-19 and control articles, respectively; p  < 0.0001). Furthermore, methodological quality scores are lower in COVID-19 articles across all study designs. COVID-19 clinical studies have a shorter time to publication and have lower methodological quality scores than control studies in the same journal. These studies should be revisited with the emergence of stronger evidence.

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Introduction

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic spread globally in early 2020 with substantial health and economic consequences. This was associated with an exponential increase in scientific publications related to the coronavirus disease 2019 (COVID-19) in order to rapidly elucidate the natural history and identify diagnostic and therapeutic tools 1 .

While a need to rapidly disseminate information to the medical community, governmental agencies, and general public was paramount—major concerns have been raised regarding the scientific rigor in the literature 2 . Poorly conducted studies may originate from failure at any of the four consecutive research stages: (1) choice of research question relevant to patient care, (2) quality of research design 3 , (3) adequacy of publication, and (4) quality of research reports. Furthermore, evidence-based medicine relies on a hierarchy of evidence, ranging from the highest level of randomized controlled trials (RCT) to the lowest level of case series and case reports 4 .

Given the implications for clinical care, policy decision making, and concerns regarding methodological and peer-review standards for COVID-19 research 5 , we performed a formal evaluation of the methodological quality of published COVID-19 literature. Specifically, we undertook a systematic review to identify COVID-19 clinical literature and matched them to historical controls to formally evaluate the following: (1) the methodological quality of COVID-19 studies using established quality tools and checklists, (2) the methodological quality of COVID-19 studies, stratified by median time to acceptance, geographical regions, and journal impact factor and (3) a comparison of COVID-19 methodological quality to matched controls.

Herein, we show that COVID-19 articles are associated with lower methodological quality scores. Moreover, in a matched cohort analysis with control articles from the same journal, we reveal that COVID-19 articles are associated with lower quality scores and shorter time from submission to acceptance. Ultimately, COVID-19 clinical studies should be revisited with the emergence of stronger evidence.

Article selection

A total of 14787 COVID-19 papers were identified as of May 14, 2020 and 4892 duplicate articles were removed. In total, 9895 titles and abstracts were screened, and 9101 articles were excluded due to the study being pre-clinical in nature, case report, case series <5 patients, in a language other than English, reviews (including systematic reviews), study protocols or methods, and other coronavirus variants with an overall inter-rater study inclusion agreement of 96.7% ( κ  = 0.81; 95% CI, 0.79–0.83). A total number of 794 full texts were reviewed for eligibility. Over 108 articles were excluded for ineligible study design or publication type (such as letter to the editors, editorials, case reports or case series <5 patients), wrong patient population, non-English language, duplicate articles, wrong outcomes and publication in a non-peer-reviewed journal. Ultimately, 686 articles were identified with an inter-rater agreement of 86.5% ( κ  = 0.68; 95% CI, 0.67–0.70) (Fig.  1 ).

A total of 14787 articles were identified and 4892 duplicate articles were removed. Overall, 9895 articles were screened by title and abstract leaving 794 articles for full-text screening. Over 108 articles were excluded, leaving a total of 686 articles that underwent methodological quality assessment.

COVID-19 literature methodological quality

Most studies originated from Asia/Oceania with 469 (68.4%) studies followed by Europe with 139 (20.3%) studies, and the Americas with 78 (11.4%) studies. Of included studies, 380 (55.4%) were case series, 199 (29.0%) were cohort, 63 (9.2%) were diagnostic, 38 (5.5%) were case–control, and 6 (0.9%) were RCTs. Most studies (590, 86.0%) were retrospective in nature, 620 (90.4%) reported the sex of patients, and 7 (2.3%) studies excluding case series calculated their sample size a priori. The method of SARS-CoV-2 diagnosis was reported in 558 studies (81.3%) and ethics approval was obtained in 556 studies (81.0%). Finally, journal impact factor of COVID-19 manuscripts was 4.7 (IQR, 2.9–7.6) with a time to acceptance of 13.0 (IQR, 5.0–25.0) days (Table  1 ).

Overall, when COVID-19 articles were stratified by study design, a mean case series score (out of 5) (SD) of 3.3 (1.1), mean NOS cohort study score (out of 8) of 5.8 (1.5), mean NOS case–control study score (out of 8) of 5.5 (1.9), and low bias present in 4 (6.4%) diagnostic studies was observed (Table  2 and Fig.  2 ). Furthermore, in the 6 RCTs in the COVID-19 literature, there was a high risk of bias with little consideration for sequence generation, allocation concealment, blinding, incomplete outcome data, and selective outcome reporting (Table  2 ).

A Distribution of COVID-19 case series studies scored using the Murad tool ( n  = 380). B Distribution of COVID-19 cohort studies scored using the Newcastle–Ottawa Scale ( n  = 199). C Distribution of COVID-19 case–control studies scored using the Newcastle–Ottawa Scale ( n  = 38). D Distribution of COVID-19 diagnostic studies scored using the QUADAS-2 tool ( n  = 63). In panel D , blue represents low risk of bias and orange represents high risk of bias.

For secondary outcomes, rapid time from submission to acceptance (stratified by median time of acceptance of <13.0 days) was associated with lower methodological quality scores for case series and cohort study designs but not for case–control nor diagnostic studies (Fig.  3A–D ). Low journal impact factor (<10) was associated with lower methodological quality scores for case series, cohort, and case–control designs (Fig.  3E–H ). Finally, studies originating from different geographical regions had no differences in methodological quality scores with the exception of cohort studies (Fig.  3I–L ). When dichotomized by high vs. low methodological quality scores, a similar trend was observed with rapid time from submission to acceptance (34.4% vs. 46.3%, p  = 0.01, Supplementary Fig.  1B ), low impact factor journals (<10) was associated with lower methodological quality score (38.8% vs. 68.0%, p  < 0.0001, Supplementary Fig.  1C ). Finally, studies originating in either Americas or Asia/Oceania was associated with higher methodological quality scores than Europe (Supplementary Fig.  1D ).

A When stratified by time of acceptance (13.0 days), increased time of acceptance was associated with higher case series score ( n  = 186 for <13 days and n  = 193 for >=13 days; p  = 0.02). B Increased time of acceptance was associated with higher NOS cohort score ( n  = 112 for <13 days and n  = 144 for >=13 days; p  = 0.003). C No difference in time of acceptance and case–control score was observed ( n  = 18 for <13 days and n  = 27 for >=13 days; p  = 0.34). D No difference in time of acceptance and diagnostic risk of bias (QUADAS-2) was observed ( n  = 43 for <13 days and n  = 33 for >=13 days; p  = 0.23). E When stratified by impact factor (IF ≥10), high IF was associated with higher case series score ( n  = 466 for low IF and n  = 60 for high IF; p  < 0.0001). F High IF was associated with higher NOS cohort score ( n  = 262 for low IF and n  = 68 for high IF; p  = 0.01). G No difference in IF and case–control score was observed ( n  = 62 for low IF and n  = 2 for high IF; p  = 0.052). H No difference in IF and QUADAS-2 was observed ( n  = 101 for low IF and n  = 2 for high IF; p  = 0.93). I When stratified by geographical region, no difference in geographical region and case series score was observed ( n  = 276 Asia/Oceania, n  = 135 Americas, and n  = 143 Europe/Africa; p  = 0.10). J Geographical region was associated with differences in cohort score ( n  = 177 Asia/Oceania, n  = 81 Americas, and n  = 89 Europe/Africa; p  = 0.01). K No difference in geographical region and case–control score was observed ( n  = 37 Asia/Oceania, n  = 13 Americas, and n  = 14 Europe/Africa; p  = 0.81). L No difference in geographical region and QUADAS-2 was observed ( n  = 49 Asia/Oceania, n  = 28 Americas, and n  = 28 Europe/Africa; p  = 0.34). In panels A – D , orange represents lower median time of acceptance and blue represents high median time of acceptance. In panels E – H , red is low impact factor and blue is high impact factor. In panels I – L , orange represents Asia/Oceania, blue represents Americas, and brown represents Europe. Differences in distributions were analysed by two-sided Kruskal–Wallis test. Differences in diagnostic risk of bias were quantified by Chi-squares test. p  < 0.05 was considered statistically significant.

Methodological quality score differences in COVID-19 versus historical control

We matched 539 historical control articles to COVID-19 articles from the same journal with identical study designs in the previous year for a final analysis of 1078 articles (Table  1 ). Overall, 554 (51.4%) case series, 348 (32.3%) cohort, 64 (5.9%) case–control, 106 (9.8%) diagnostic and 6 (0.6%) RCTs were identified from the 1078 total articles. Differences exist between COVID-19 and historical control articles in geographical region of publication, retrospective study design, and sample size calculation (Table  1 ). Time of acceptance was 13.0 (IQR, 5.0–25.0) days in COVID-19 articles vs. 110.0 (IQR, 71.0–156.0) days in control articles (Table  1 and Fig.  4A , p  < 0.0001). Case-series methodological quality score was lower in COVID-19 articles compared to the historical control (3.3 (1.1) vs. 4.3 (0.8); n  = 554; p  < 0.0001; Table  2 and Fig.  4B ). Furthermore, NOS score was lower in COVID-19 cohort studies (5.8 (1.6) vs. 7.1 (1.0); n  = 348; p  < 0.0001; Table  2 and Fig.  4C ) and case–control studies (5.4 (1.9) vs. 6.6 (1.0); n  = 64; p  = 0.003; Table  2 and Fig.  4D ). Finally, lower risk of bias in diagnostic studies was in 12 COVID-19 articles (23%; n  = 53) compared to 24 control articles (45%; n  = 53; p  = 0.02; Table  2 and Fig.  4E ). A similar trend was observed between COVID-19 and historical control articles when dichotomized by good vs. low methodological quality scores (Supplementary Fig.  2 ).

A Time to acceptance was reduced in COVID-19 articles compared to control articles (13.0 [IQR, 5.0–25.0] days vs. 110.0 [IQR, 71.0–156.0] days, n  = 347 for COVID-19 and n  = 414 for controls; p  < 0.0001). B When compared to historical control articles, COVID-19 articles were associated with lower case series score ( n  = 277 for COVID-19 and n  = 277 for controls; p  < 0.0001). C COVID-19 articles were associated with lower NOS cohort score compared to historical control articles ( n  = 174 for COVID-19 and n  = 174 for controls; p  < 0.0001). D COVID-19 articles were associated with lower NOS case–control score compared to historical control articles ( n  = 32 for COVID-19 and n  = 32 for controls; p  = 0.003). E COVID-19 articles were associated with higher diagnostic risk of bias (QUADAS-2) compared to historical control articles ( n  = 53 for COVID-19 and n  = 53 for controls; p  = 0.02). For panel A , boxplot captures 5, 25, 50, 75 and 95% from the first to last whisker. Orange represents COVID-19 articles and blue represents control articles. Two-sided Mann–Whitney U-test was conducted to evaluate differences in time to acceptance between COVID-19 and control articles. Differences in study quality scores were evaluated by two-sided Kruskal–Wallis test. Differences in diagnostic risk of bias were quantified by Chi-squares test. p  < 0.05 was considered statistically significant.

In this systematic evaluation of methodological quality, COVID-19 clinical research was primarily observational in nature with modest methodological quality scores. Not only were the study designs low in the hierarchy of scientific evidence, we found that COVID-19 articles were associated with a lower methodological quality scores when published with a shorter time of publication and in lower impact factor journals. Furthermore, in a matched cohort analysis with historical control articles identified from the same journal of the same study design, we demonstrated that COVID-19 articles were associated with lower quality scores and shorter time from submission to acceptance.

The present study demonstrates comparative differences in methodological quality scores between COVID-19 literature and historical control articles. Overall, the accelerated publication of COVID-19 research was associated with lower study quality scores compared to previously published historical control studies. Our research highlights major differences in study quality between COVID-19 and control articles, possibly driven in part by a combination of more thorough editorial and/or peer-review process as suggested by the time to publication, and robust study design with questions which are pertinent for clinicians and patient management 3 , 6 , 7 , 8 , 9 , 10 , 11 .

In the early stages of the COVID-19 pandemic, we speculate that an urgent need for scientific data to inform clinical, social and economic decisions led to shorter time to publication and explosion in publication of COVID-19 studies in both traditional peer-reviewed journals and preprint servers 1 , 12 . The accelerated scientific process in the COVID-19 pandemic allowed a rapid understanding of natural history of COVID-19 symptomology and prognosis, identification of tools including RT-PCR to diagnose SARS-CoV-2 13 , and identification of potential therapeutic options such as tocilizumab and convalescent plasma which laid the foundation for future RCTs 14 , 15 , 16 . A delay in publication of COVID-19 articles due to a slower peer-review process may potentially delay dissemination of pertinent information against the pandemic. Despite concerns of slow peer review, major landmark trials (i.e. RECOVERY and ACTT-1 trial) 17 , 18 published their findings in preprint servers and media releases to allow for rapid dissemination. Importantly, the data obtained in these initial studies should be revisited as stronger data emerges as lower quality studies may fundamentally risk patient safety, resource allocation and future scientific research 19 .

Unfortunately, poor evidence begets poor clinical decisions 20 . Furthermore, lower quality scientific evidence potentially undermines the public’s trust in science during this time and has been evident through misleading information and high-profile retractions 12 , 21 , 22 , 23 . For example, the benefits of hydroxychloroquine, which were touted early in the pandemic based on limited data, have subsequently failed to be replicated in multiple observational studies and RCTs 5 , 24 , 25 , 26 , 27 , 28 , 29 , 30 . One poorly designed study combined with rapid publication led to considerable investment of both the scientific and medical community—akin to quinine being sold to the public as a miracle drug during the 1918 Spanish Influenza 31 , 32 . Moreover, as of June 30, 2020, ClinicalTrials.gov listed an astonishing 230 COVID-19 trials with hydroxychloroquine/plaquenil, and a recent living systematic review of observational studies and RCTs of hydroxychloroquine or chloroquine for COVID-19 demonstrated no evidence of benefit nor harm with concerns of severe methodological flaws in the included studies 33 .

Our study has important limitations. We evaluated the methodological quality of existing studies using established checklists and tools. While it is tempting to associate methodological quality scores with reproducibility or causal inferences of the intervention, it is not possible to ascertain the impact on the study design and conduct of research nor results or conclusions in the identified reports 34 . Second, although the methodological quality scales and checklists used for the manuscript are commonly used for quality assessment in systematic reviews and meta-analyses 35 , 36 , 37 , 38 , they can only assess the methodology without consideration for causal language and are prone to limitations 39 , 40 . Other tools such as the ROBINS-I and GRADE exist to evaluate methodological quality of identified manuscripts, although no consensus currently exists for critical appraisal of non-randomized studies 41 , 42 , 43 . Furthermore, other considerations of quality such as sample size calculation, sex reporting or ethics approval are not considered in these quality scores. As such, the quality scores measured using these checklists only reflect the patient selection, comparability, diagnostic reference standard and methods to ascertain the outcome of the study. Third, the 1:1 ratio to identify our historical control articles may affect the precision estimates of our findings. Interestingly, a simulation of an increase from 1:1 to 1:4 control ratio tightened the precision estimates but did not significantly alter the point estimate 44 . Furthermore, the decision for 1:1 ratio in our study exists due to limitations of available historical control articles from the identical journal in the restricted time period combined with a large effect size and sample size in the analysis. Finally, our analysis includes early publications on COVID-19 and there is likely to be an improvement in quality of related studies and study design as the field matures and higher-quality studies. Accordingly, our findings are limited to the early body of research as it pertains to the pandemic and it is likely that over time research quality will improve over time.

In summary, the early body of peer-reviewed COVID-19 literature was composed primarily of observational studies that underwent shorter peer-review evaluation and were associated with lower methodological quality scores than comparable studies. COVID-19 clinical studies should be revisited with the emergence of stronger evidence.

A systematic literature search was conducted on May 14, 2020 (registered on June 3, 2020 at PROSPERO: CRD42020187318) and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Furthermore, the cohort study was reported according to the Strengthening The Reporting of Observational Studies in Epidemiology checklist. The data supporting the findings of this study is available as Supplementary Data  1 – 2 .

Data sources and searches

The search was created in MEDLINE by a medical librarian with expertise in systematic reviews (S.V.) using a combination of key terms and index headings related to COVID-19 and translated to the remaining bibliographic databases (Supplementary Tables  1 – 3 ). The searches were conducted in MEDLINE (Ovid MEDLINE(R) ALL 1946–), Embase (Ovid Embase Classic + Embase 1947–) and the Cochrane Central Register of Controlled Trials (from inception). Search results were limited to English-only publications, and a publication date limit of January 1, 2019 to present was applied. In addition, a Canadian Agency for Drugs and Technologies in Health search filter was applied in MEDLINE and Embase to remove animal studies, and commentary, newspaper article, editorial, letter and note publication types were also eliminated. Search results were exported to Covidence (Veritas Health Innovation, Melbourne, Australia) and duplicates were eliminated using the platform’s duplicate identification feature.

Study selection, data extraction and methodological quality assessment

We included all types of COVID-19 clinical studies, including case series, observational studies, diagnostic studies and RCTs. For diagnostic studies, the reference standard for COVID-19 diagnosis was defined as a nasopharyngeal swab followed by reverse transcriptase-polymerase chain reaction in order to detect SARS-CoV-2. We excluded studies that were exploratory or pre-clinical in nature (i.e. in vitro or animal studies), case reports or case series of <5 patients, studies published in a language other than English, reviews, methods or protocols, and other coronavirus variants such as the Middle East respiratory syndrome.

The review team consisted of trained research staff with expertise in systematic reviews and one trainee. Title and abstracts were evaluated by two independent reviewers using Covidence and all discrepancies were resolved by consensus. Articles that were selected for full review were independently evaluated by two reviewers for quality assessment using a standardized case report form following the completion of a training period where all reviewers were trained with the original manuscripts which derived the tools or checklists along with examples for what were deemed high scores 35 , 36 , 37 , 38 . Following this, reviewers completed thirty full-text extractions and the two reviewers had to reach consensus and the process was repeated for the remaining manuscripts independently. When two independent reviewers were not able reach consensus, a third reviewer (principal investigator) provided oversight in the process to resolve the conflicted scores.

First and corresponding author names, date of publication, title of manuscript and journal of publication were collected for all included full-text articles. Journal impact factor was obtained from the 2018 InCites Journal Citation Reports from Clarivate Analytics. Submission and acceptance dates were collected in manuscripts when available. Other information such as study type, prospective or retrospective study, sex reporting, sample size calculation, method of SARS-CoV-2 diagnosis and ethics approval was collected by the authors. Methodological quality assessment was conducted using the Newcastle–Ottawa Scale (NOS) for case–control and cohort studies 37 , QUADAS-2 tool for diagnostic studies 38 , Cochrane risk of bias for RCTs 35 and a score derived by Murad et al. for case series studies 36 .

Identification of historical control from identified COVID-19 articles

Following the completion of full-text extraction of COVID-19 articles, we obtained a historical control group by identifying reports matched in a 1:1 fashion. From the eligible COVID-19 article, historical controls were identified by searching the same journal in a systematic fashion by matching the same study design (“case series”, “cohort”, “case control” or “diagnostic”) starting in the journal edition 12 months prior to the COVID-19 article publication on the publisher website (i.e. COVID-19 article published on April 2020, going backwards to April 2019) and proceeding forward (or backward if a specific article type was not identified) in a temporal fashion until the first matched study was identified following abstract screening by two independent reviewers. If no comparison article was found by either reviewers, the corresponding COVID-19 article was excluded from the comparison analysis. Following the identification of the historical control, data extraction and quality assessment was conducted on the identified articles using the standardized case report forms by two independent reviewers and conflicts resolved by consensus. The full dataset has been made available as Supplementary Data  1 – 2 .

Data synthesis and statistical analysis

Continuous variables were reported as mean (SD) or median (IQR) as appropriate, and categorical variables were reported as proportions (%). Continuous variables were compared using Student t -test or Mann–Whitney U-test and categorical variables including quality scores were compared by χ 2 , Fisher’s exact test, or Kruskal–Wallis test.

The primary outcome of interest was to evaluate the methodological quality of COVID-19 clinical literature by study design using the Newcastle–Ottawa Scale (NOS) for case–control and cohort studies, QUADAS-2 tool for diagnostic studies 38 , Cochrane risk of bias for RCTs 35 , and a score derived by Murad et al. for case series studies 36 . Pre-specified secondary outcomes were comparison of methodological quality scores of COVID-19 articles by (i) median time to acceptance, (ii) impact factor, (iii) geographical region and (iv) historical comparator. Time of acceptance was defined as the time between submission to acceptance which captures peer review and editorial decisions. Geographical region was stratified into continents including Asia/Oceania, Europe/Africa and Americas (North and South America). Post hoc comparison analysis between COVID-19 and historical control article quality scores were evaluated using Kruskal–Wallis test. Furthermore, good quality of NOS was defined as 3+ on selection and 1+ on comparability, and 2+ on outcome/exposure domains and high-quality case series scores was defined as a score ≥3.5. Due to a small sample size of identified RCTs, they were not included in the comparison analysis.

The finalized dataset was collected on Microsoft Excel v16.44. All statistical analyses were performed using SAS v9.4 (SAS Institute, Inc., Cary, NC, USA). Statistical significance was defined as P  < 0.05. All figures were generated using GraphPad Prism v8 (GraphPad Software, La Jolla, CA, USA).

Reporting summary

Further information on research design is available in the  Nature Research Reporting Summary linked to this article.

Data availability

The authors can confirm that all relevant data are included in the paper and in Supplementary Data  1 – 2 . The original search was conducted on MEDLINE, Embase and Cochrane Central Register of Controlled Trials.

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Acknowledgements

This study received no specific funding or grant from any agency in the public, commercial, or not-for-profit sectors. R.G.J. was supported by the Vanier CIHR Canada Graduate Scholarship. F.D.R. was supported by a CIHR Banting Postdoctoral Fellowship and a Royal College of Physicians and Surgeons of Canada Detweiler Travelling Fellowship. The funder/sponsor(s) had no role in design and conduct of the study, collection, analysis and interpretation of the data.

Author information

These authors contributed equally: Richard G. Jung, Pietro Di Santo.

Authors and Affiliations

CAPITAL Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada

Richard G. Jung, Pietro Di Santo, F. Daniel Ramirez & Trevor Simard

Vascular Biology and Experimental Medicine Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada

Richard G. Jung, Pietro Di Santo, Trevor Simard & Benjamin Hibbert

Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada

Richard G. Jung, Trevor Simard & Benjamin Hibbert

Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada

Pietro Di Santo, Simon Parlow, F. Daniel Ramirez, Trevor Simard & Benjamin Hibbert

School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada

Pietro Di Santo

Faculty of Medicine, University of Ottawa, Ontario, Canada

Cole Clifford & Stephanie Skanes

Department of Medicine, Cumming School of Medicine, Calgary, Alberta, Canada

Graeme Prosperi-Porta

Division of Internal Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada

Berkman Library, University of Ottawa Heart Institute, Ottawa, Ontario, Canada

Sarah Visintini

Hôpital Cardiologique du Haut-Lévêque, CHU Bordeaux, Bordeaux-Pessac, France

F. Daniel Ramirez

L’Institut de Rythmologie et Modélisation Cardiaque (LIRYC), University of Bordeaux, Bordeaux, France

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA

Trevor Simard

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Contributions

R.G.J., P.D.S., S.V., F.D.R., T.S. and B.H. participated in the study conception and design. Data acquisition, analysis and interpretation were performed by R.G.J., P.D.S., C.C., G.P.P., S.P., S.S., A.H., F.D.R., T.S. and B.H. Statistical analysis was performed by R.G.J., P.D.S. and B.H. The manuscript was drafted by R.G.J., P.D.S., F.D.R., T.S. and B.H. All authors approved the final version of the manuscript and agree to be accountable to all aspects of the work.

Corresponding author

Correspondence to Benjamin Hibbert .

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Competing interests.

B.H. reports funding as a clinical trial investigator from Abbott, Boston Scientific and Edwards Lifesciences outside of the submitted work. The remaining authors declare no competing interests.

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How to Write About Coronavirus in a College Essay

Students can share how they navigated life during the coronavirus pandemic in a full-length essay or an optional supplement.

Writing About COVID-19 in College Essays

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Experts say students should be honest and not limit themselves to merely their experiences with the pandemic.

The global impact of COVID-19, the disease caused by the novel coronavirus, means colleges and prospective students alike are in for an admissions cycle like no other. Both face unprecedented challenges and questions as they grapple with their respective futures amid the ongoing fallout of the pandemic.

Colleges must examine applicants without the aid of standardized test scores for many – a factor that prompted many schools to go test-optional for now . Even grades, a significant component of a college application, may be hard to interpret with some high schools adopting pass-fail classes last spring due to the pandemic. Major college admissions factors are suddenly skewed.

"I can't help but think other (admissions) factors are going to matter more," says Ethan Sawyer, founder of the College Essay Guy, a website that offers free and paid essay-writing resources.

College essays and letters of recommendation , Sawyer says, are likely to carry more weight than ever in this admissions cycle. And many essays will likely focus on how the pandemic shaped students' lives throughout an often tumultuous 2020.

But before writing a college essay focused on the coronavirus, students should explore whether it's the best topic for them.

Writing About COVID-19 for a College Application

Much of daily life has been colored by the coronavirus. Virtual learning is the norm at many colleges and high schools, many extracurriculars have vanished and social lives have stalled for students complying with measures to stop the spread of COVID-19.

"For some young people, the pandemic took away what they envisioned as their senior year," says Robert Alexander, dean of admissions, financial aid and enrollment management at the University of Rochester in New York. "Maybe that's a spot on a varsity athletic team or the lead role in the fall play. And it's OK for them to mourn what should have been and what they feel like they lost, but more important is how are they making the most of the opportunities they do have?"

That question, Alexander says, is what colleges want answered if students choose to address COVID-19 in their college essay.

But the question of whether a student should write about the coronavirus is tricky. The answer depends largely on the student.

"In general, I don't think students should write about COVID-19 in their main personal statement for their application," Robin Miller, master college admissions counselor at IvyWise, a college counseling company, wrote in an email.

"Certainly, there may be exceptions to this based on a student's individual experience, but since the personal essay is the main place in the application where the student can really allow their voice to be heard and share insight into who they are as an individual, there are likely many other topics they can choose to write about that are more distinctive and unique than COVID-19," Miller says.

Opinions among admissions experts vary on whether to write about the likely popular topic of the pandemic.

"If your essay communicates something positive, unique, and compelling about you in an interesting and eloquent way, go for it," Carolyn Pippen, principal college admissions counselor at IvyWise, wrote in an email. She adds that students shouldn't be dissuaded from writing about a topic merely because it's common, noting that "topics are bound to repeat, no matter how hard we try to avoid it."

Above all, she urges honesty.

"If your experience within the context of the pandemic has been truly unique, then write about that experience, and the standing out will take care of itself," Pippen says. "If your experience has been generally the same as most other students in your context, then trying to find a unique angle can easily cross the line into exploiting a tragedy, or at least appearing as though you have."

But focusing entirely on the pandemic can limit a student to a single story and narrow who they are in an application, Sawyer says. "There are so many wonderful possibilities for what you can say about yourself outside of your experience within the pandemic."

He notes that passions, strengths, career interests and personal identity are among the multitude of essay topic options available to applicants and encourages them to probe their values to help determine the topic that matters most to them – and write about it.

That doesn't mean the pandemic experience has to be ignored if applicants feel the need to write about it.

Writing About Coronavirus in Main and Supplemental Essays

Students can choose to write a full-length college essay on the coronavirus or summarize their experience in a shorter form.

To help students explain how the pandemic affected them, The Common App has added an optional section to address this topic. Applicants have 250 words to describe their pandemic experience and the personal and academic impact of COVID-19.

"That's not a trick question, and there's no right or wrong answer," Alexander says. Colleges want to know, he adds, how students navigated the pandemic, how they prioritized their time, what responsibilities they took on and what they learned along the way.

If students can distill all of the above information into 250 words, there's likely no need to write about it in a full-length college essay, experts say. And applicants whose lives were not heavily altered by the pandemic may even choose to skip the optional COVID-19 question.

"This space is best used to discuss hardship and/or significant challenges that the student and/or the student's family experienced as a result of COVID-19 and how they have responded to those difficulties," Miller notes. Using the section to acknowledge a lack of impact, she adds, "could be perceived as trite and lacking insight, despite the good intentions of the applicant."

To guard against this lack of awareness, Sawyer encourages students to tap someone they trust to review their writing , whether it's the 250-word Common App response or the full-length essay.

Experts tend to agree that the short-form approach to this as an essay topic works better, but there are exceptions. And if a student does have a coronavirus story that he or she feels must be told, Alexander encourages the writer to be authentic in the essay.

"My advice for an essay about COVID-19 is the same as my advice about an essay for any topic – and that is, don't write what you think we want to read or hear," Alexander says. "Write what really changed you and that story that now is yours and yours alone to tell."

Sawyer urges students to ask themselves, "What's the sentence that only I can write?" He also encourages students to remember that the pandemic is only a chapter of their lives and not the whole book.

Miller, who cautions against writing a full-length essay on the coronavirus, says that if students choose to do so they should have a conversation with their high school counselor about whether that's the right move. And if students choose to proceed with COVID-19 as a topic, she says they need to be clear, detailed and insightful about what they learned and how they adapted along the way.

"Approaching the essay in this manner will provide important balance while demonstrating personal growth and vulnerability," Miller says.

Pippen encourages students to remember that they are in an unprecedented time for college admissions.

"It is important to keep in mind with all of these (admission) factors that no colleges have ever had to consider them this way in the selection process, if at all," Pippen says. "They have had very little time to calibrate their evaluations of different application components within their offices, let alone across institutions. This means that colleges will all be handling the admissions process a little bit differently, and their approaches may even evolve over the course of the admissions cycle."

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In a pandemic milestone, the NIH ends guidance on COVID treatment

Pfizer's Paxlovid combines two antiviral drugs to fight the virus that causes COVID-19. Joe Raedle/Getty Images hide caption

Pfizer's Paxlovid combines two antiviral drugs to fight the virus that causes COVID-19.

These days, if you're sick with COVID-19 and you're at risk of getting worse, you could take pills like Paxlovid or get an antiviral infusion.

By now, these drugs have a track record of doing pretty well at keeping people with mild to moderate COVID-19 out of the hospital.

The availability of COVID-19 treatments has evolved over the past four years, pushed forward by the rapid accumulation of data and by scientists and doctors who pored over every new piece of information to create evidence-based guidance on how to best care for COVID-19 patients.

One very influential set of guidelines — viewed more than 50 million times and used by doctors around the world — is the COVID-19 Treatment Guidelines from the National Institutes of Health (NIH).

"I think everyone [reading this] will remember [spring of] 2020, when we did not know how to treat COVID and around the country, people were trying different things," recalls Dr. Rajesh Gandhi , an infectious diseases specialist at Massachusetts General Hospital and a member of the NIH's COVID-19 Treatment Guidelines Panel. Around that time, people were popping tablets of hydroxychloroquine and buying livestock stores out of ivermectin, when there was no proof that either of these drugs worked against infection by the coronavirus that causes COVID-19 ( later studies showed that they are ineffective ).

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Nih panel recommends against drug combination promoted by trump for covid-19.

It was early in the COVID-19 pandemic when the NIH convened a panel of more than 40 experts and put out its first guidelines, which became a reference for doctors around the world.

For the next few years, it was an "all hands on deck" endeavor, says Dr. Cliff Lane , director of the clinical research division at the National Institute of Allergy and Infectious Diseases (NIAID) and a co-chair of the panel.

Panel members met several times a week to review the latest scientific literature and debate data in preprints. They updated their official guidance frequently, sometimes two or three times a month.

End of an era

Lately, the development of new COVID-19 treatments has slowed to a drip, prompting the guideline group to rethink its efforts. "I don't know that there was a perfect moment [to end it], but ... the frequency of calls that we needed to have began to decrease, and then on occasion we would be canceling one of our regularly scheduled calls," says Lane. "It's probably six months ago we started talking about — What will be the end? How do we end it in a way that we don't create a void?"

The last version of the NIH's COVID-19 Treatment Guidelines was issued in February. The archives of the guidance — available online until August — document how scientific understanding and technological progress evolved during the pandemic.

Lane says specialty doctors groups — such as the American College of Physicians and the Infectious Diseases Society of America — will be the keepers of COVID-19 treatment guidance from now on. They're the usual stewards of best-practice guidelines anyway, he says.

At this transition point, panel members say the evolution of COVID-19 treatments offers lessons for dealing with new emerging infectious diseases.

Turning points in treatment

In the spring of 2020, hospitals in parts of the U.S. were filling up with the first pandemic wave of COVID-19 patients. "We were just learning how the disease progressed. Our first guideline [ issued that April ] was, basically, we don't know what does and doesn't work," says Gandhi, of Massachusetts General Hospital. "But we did learn fairly quickly — mostly in hospitalized patients — what did work."

By June 2020, data supported a treatment plan for very ill patients: Use steroids like dexamethasone to stop the body's immune system from attacking itself, and combine them with antivirals, to stop the virus from replicating.

Then, about a year into the pandemic, came another turning point: solid evidence that early treatment with lab-made antibodies could help keep COVID-19 patients out of the hospital. "This was a somewhat unexpected and dramatic [positive] effect," Lane says, noting that previous attempts to develop antibody therapies against influenza were unsuccessful.

The way these drugs, called monoclonal antibodies, worked out "provided so much insight into the virus itself," says Dr. Phyllis Tien , of the University of California, San Francisco, and a member of the COVID-19 treatment panel. While initially successful, the antibodies targeted the coronavirus's fast-changing spike protein. New strains of the coronavirus would knock out each new antibody version in about a year .

This cat-and-mouse strategy didn't last.

Shots - Health News

How monoclonal antibodies lost the fight with new covid variants.

By the end of 2021, the Food and Drug Administration authorized two pill courses that COVID-19 patients could try taking at home to get better: Merck's molnupiravir and Pfizer's Paxlovid, a combination of two antiviral drugs: ritonavir and nirmatrelvir.

"Both have, as I like to say, warts," says Carl Dieffenbach , director of the AIDS division at NIAID and part of the agency's program to develop antivirals for pandemics. "Molnupiravir's warts are that it works marginally," meaning the data shows that it isn't very effective. And while Paxlovid works pretty well, it can't be taken with a lot of common drugs. "[Many] doctors are uncomfortable or unwilling to manage ... [patients] who should take it, but are on a statin or some other drug through the process," Dieffenbach says.

Another antiviral drug, remdesivir , is also considered fairly effective for treating mild to moderate COVID-19, though it's harder for patients to access, as it's administered intravenously. The drug company Gilead tried to make it into a pill, but it didn't work .

Underuse of effective treatment

The hurdles that come with each of these outpatient treatments have contributed to low usage rates among the patients they're intended to help, says Jenny Shen , a research scientist at the CUNY Institute for Implementation Science in Population Health.

Shen's research found that at the height of the pandemic, just 2% of COVID-19 patients reported getting molnupiravir and 15% reported getting Paxlovid, among those considered to be eligible for the drugs.

The study uses data from 2021-2022 — a time when the federal government bought these drugs from manufacturers and provided them free to states, health centers and pharmacies. Shen notes that rates of use have likely further declined since late 2023, after the drugs got transitioned to the commercial market , since they're "not as free as before" and, in many cases, require copayments.

Goats and Soda

Coronavirus faq: is paxlovid the best treatment is it underused in the u.s..

Another part of the problem is that doctors can be reluctant to prescribe these outpatient treatments, since they can be difficult to manage if a patient has other health problems, Shen says.

Yet another challenge is that many patients with risk factors just don't believe they'll get very sick. "A dilemma we have observed is that patients want to see how severe their disease may become," but in waiting, they become ill beyond the point where the treatment would help, Shen says.

Even now, when some 13,000 people are getting hospitalized with COVID-19 each week, more patient education on how the drugs work and when they're most effective could help those who are sick make better-informed decisions, she says.

There's one more COVID-19 drug in late-stage clinical trials that could be promising, says Dieffenbach. It's a pill course by the Japanese company Shionogi that's getting tested for its efficacy against both acute and long COVID. "I'm waiting to see how this all turns out," he says, "But then that's it. That's what's in the pipeline" for the near future.

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Exercise Therapy for Post–COVID-19 Condition—Does No Harm

• 1 Academic Department of Military Rehabilitation, Defence Medical Rehabilitation Centre (DMRC) Stanford Hall, Loughborough, United Kingdom
• 2 Department for Health, University of Bath, Bath, United Kingdom
• 3 National Heart and Lung Institute, Imperial College London, London, United Kingdom
• 4 Academic Unit of Injury, Recovery and Inflammation Science, School of Medicine, University of Nottingham, Nottingham, United Kingdom
• Original Investigation Exercise Intolerance in Patients With Post-COVID Condition Andrea Tryfonos, PhD; Kaveh Pourhamidi, MD, PhD; Gustav Jörnåker, MSc; Martin Engvall, MD; Lisa Eriksson, MSc; Sara Elhallos, BSc; Nicole Asplund; Mirko Mandić, PhD; Patrik Sundblad, MD, PhD; Atif Sepic, MSc; Eric Rullman, MD, PhD; Lars Hyllienmark, MD, PhD; Helene Rundqvist, PhD; Tommy R. Lundberg, PhD; Thomas Gustafsson, MD, PhD JAMA Network Open

International guidelines from public health organizations, including the World Health Organization, caution against graded exercise for treating patients with postexertional symptom exacerbation (PESE), a commonly reported feature of post–COVID-19 condition (PCC). These recommendations are provided despite the well-documented deleterious effects of physical inactivity and its close association with secondary health conditions and deterioration in quality of life. Subsequently, there has been confusion and reluctance among health care practitioners to prescribe exercise-based rehabilitation to individuals with PCC to avoid the debilitating effects of postexertional malaise, fatigue, or PESE. Consequently, the effects of exercise-based rehabilitation for individuals with persistent PESE remain poorly understood. Studies have shown that among individuals with PCC, up to 48% of female individuals and 41% of male individuals experience postexertional malaise, and 29% of female individuals and 28% of male individuals experience orthostatic intolerance. 1 The article by Tryfonos and colleagues 2 is, therefore, timely and necessary because it addresses an important topic in the debate surrounding patient acceptability and the therapeutic effects of different exercise modalities in the treatment of patients with PCC and their acute risks of developing PESE.

Tryfonos et al 2 recruited 31 nonhospitalized, community-based participants with a mean (SD) symptom duration of 21.6 (9.2) months following COVID-19 illness (with 31 age-matched and sex-matched healthy controls for comparison). This previously healthy and working-age population represents an important section of society; 78% of the PCC group were employed full-time before SARS-CoV-2 infection. Subsequently, 74% had to take sick leave lasting longer than 12 months. PCC, therefore, has a substantial economic impact on nonhospitalized, working-aged individuals, a challenge that is magnified if job roles are cognitively and/or physically demanding. 3 The careful introduction and future management of exercise therapy in the treatment of individuals with postviral conditions has been previously proposed following a comprehensive needs analysis to mitigate PESE. 4 This can be achieved by individually tailoring exercise prescription and/or management and incorporating both resistance exercise and cardiorespiratory fitness, in an approach termed symptom-guided exercise rehabilitation . 4 Testing this theory, Tryfonos and colleagues 2 monitored the acute effects of 3 different types of exercise stimulus in those with PESE, compared with healthy controls, aware that patients with PCC spent 43% less time in moderate-to-vigorous physical activity compared with controls (approximately 26.5 minutes per day). The 3 exercise modalities were (1) high-intensity interval training (HIIT), (2) moderate-intensity continuous training (MICT), and strength-based training (ST) performed in a randomized, crossover design with 2 to 4 weeks of washout between sessions. The primary outcome measure was the difference in fatigue level (from baseline to 48 hours after exercise) between groups. The authors chose this time, citing that those with phenotypically similar myalgic encephalomyelitis–chronic fatigue syndrome commonly report PESE between 24 and 72 hours after exertion. Reassuringly, there were no between-group differences in fatigue 48 hours after any exercise modality (HIIT, MICT, or ST). However, subtle differences in self-reported symptoms were observed following each exercise condition, with patients with PCC reporting higher levels of concentration impairment following MICT and greater increases in muscle soreness after ST (commensurate with delayed onset of muscle soreness, which is expected after completing unfamiliar loaded resistance exercise).

Compared with healthy controls, the PCC group had higher overall self-reported symptom scores at all time points (before exercise, immediately after exercise, and at 48 hours follow-up) alongside substantial physiological characteristics; indeed, a particular strength of this study 2 is the range of physiological assessments undertaken. The PCC group demonstrated underlying dysfunction in multiple organ systems that may contribute to activity limitations, including muscular impairment (ie, higher incidence of myogenic-derived myopathies observed alongside decreased isometric muscle strength), indices of orthostatic intolerance, lower peak and submaximal aerobic capacity (ie, maximal oxygen consumption at peak and ventilatory threshold), lower heart rate variability (recorded during deep breathing), higher resting heart rate, and increased arterial stiffness. Tryfonos et al 2 proposed mechanisms, including physical inactivity, peripheral tissue damage, and/or neurophysiological changes, for these physiological limitations, echoing findings from other research groups. 5 These clinical manifestations present a complex rehabilitation challenge, requiring modulation of activity duration and/or intensity, with concurrent pacing, to avoid PESE or fatigue.

Debunking the controversies surrounding graded exercise therapy, reinforcing the importance of physical activity, and integrating resistance exercise and cardiorespiratory fitness into the rehabilitation programs for individuals with postviral conditions formed the basis of a recent clinical commentary. 4 The article by Tryfonos and colleagues 2 reinforces some of those key messages with quantifiable data. The ability of individuals with PCC to tolerate various exercise activities, particularly hard-intensity activities (scoring ≥16 on the 6-20 rate of perceived exertion Borg scale) without major escalation of symptoms, fatigue, or exercise capacity is important for advancing rehabilitation provision and practice in those with PESE. From an exercise prescription perspective, continued engagement with either endurance-based exercise session (HIIT and MICT) provides the opportunity to improve cardiorespiratory fitness. Importantly, both exercise types meet patient acceptability, do not exacerbate symptoms of fatigue, and provide options to patients with PCC regarding individual training preferences (vigorous-intensity 10-minute HIIT session vs moderate-intensity, 30-minute MICT session).

This study 2 demonstrates the acute response to different exercise modalities, which was largely comparable between groups with no profound symptom exacerbation. These findings are extremely important as a proof of concept but require a longitudinal trial to determine whether these exercise modalities remain feasible to deliver in a community setting, are acceptable on behalf of the patient, and elicit favorable longer-term outcomes. However, it is important to note that this study involved individuals with no known comorbidities. Prescreening and appropriate adjustments to exercise volume and/or intensity may be warranted when accommodating secondary health conditions and to a wider population. We recognize that greater rehabilitation support, education, and creativity may be warranted to attain favorable long-term changes in physical function and counteract the effects of prolonged muscle deconditioning in individuals with complex rehabilitation needs. If these exercise sessions can be carefully incorporated into a longitudinal exercise protocol, they may have far-reaching positive health consequences for individuals with PCC, including improvements in cardiorespiratory, musculoskeletal, and mental health, with subsequently reduced work absenteeism. Further complementing this study’s findings is a recent prospective cohort study 6 that reported increased physical activity levels alongside reductions in PESE episodes (from 3.4 to 1.1 per week) following a supervised progressively structured 6-week pacing protocol within a post–COVID-19 rehabilitation service.

Given the consequences of physical inactivity on muscle mass, muscle strength, and cardiorespiratory fitness, strategies that encourage participation in exercise rehabilitation programs are vital if we are to rehabilitate and reintegrate individuals with PCC back into society and/or employment. 4 We would, therefore, like to end this commentary by quoting the authors’ 2 concluding sentences from their article: “However, given that exercise was generally well tolerated, guidelines cautioning against exercise in similar populations may need to be revised. It seems advisable to cautiously incorporate exercise into rehabilitation protocols and adjust the intensity progressively, considering patients’ symptoms and abilities.” 2

Published: April 4, 2024. doi:10.1001/jamanetworkopen.2024.6959

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2024 Ladlow P et al. JAMA Network Open .

Corresponding Author: Peter Ladlow, PhD, Academic Department of Military Rehabilitation, Defence Medical Rehabilitation Centre (DMRC) Stanford Hall, Loughborough LE12 5BL, United Kingdom ( [email protected] ).

Conflict of Interest Disclosures: None reported.

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Ladlow P , Bennett AN , O’Sullivan O. Exercise Therapy for Post–COVID-19 Condition—Does No Harm. JAMA Netw Open. 2024;7(4):e246959. doi:10.1001/jamanetworkopen.2024.6959

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An effective treatment for COVID-19 is underused, research shows

A safe and effective medication designed to prevent mild-to-moderate COVID-19 infections from becoming more dangerous has been available for almost two years. But recent studies have shown many patients eligible for the drug—Paxlovid—haven't been prescribed it.

In a clinical trial, the orally taken medication reduced the risk of hospitalization and death by 86%. Paxlovid was fully approved by the Food and Drug Administration in May 2023 but has been available through an emergency use authorization since 2022.

A pre-print study available on medRxiv of more than a million COVID-19 patients found that less than 10% of eligible patients were prescribed Paxlovid, also known as nirmatrelvir-ritonavir. The reasons behind the treatment's slow uptake could include confusion over who's eligible or even unfamiliarity with the drug.

How does it work?

The antiviral drug works to stop the replication of the virus which causes COVID-19 at the cellular level. It comes as a dose pack; two of the pills are the active medicine, nirmatrelvir, and one is a "booster" medicine, ritonavir, which helps the nirmatrelvir maintain effective levels in the bloodstream.

Paxlovid is most effective when taken within five days of developing symptoms.

Who's eligible?

The treatment is designed for high-risk patients who have a mild or moderate case of COVID-19 but hope to avoid more severe consequences. You might be considered high-risk if you're:

• Not up to date on COVID vaccinations
• Immunocompromised
• Or have any other medical conditions like diabetes, hypertension or asthma

A full list of medical conditions that may leave you at high-risk for a severe case of COVID-19 are listed on the CDC's website here.

When should I ask my doctor about Paxlovid?

If you are at high-risk for complications from COVID-19, it's best not to wait before asking your doctor about Paxlovid. The treatment should be taken within five days of the onset of symptoms.

A study from the University of Hong Kong, published in Nature Communications , which analyzed data from more than 87,000 patients who took nirmatrelvir-ritonavir, found that earlier treatment even within that five-day window leads to better outcomes.

The treatment will be free for Medicare or Medicaid beneficiaries through the end of 2024 via the U.S. government's Patient Assistance Program. Those with private insurance can enroll in the Paxcess program to help lower out-of-pocket costs.

When you ask your health care provider about Paxlovid, make sure to update them on all other medications you are taking. While most medications are generally safe to take with Paxlovid, there are some which need dose adjustments or should be held during and for a short while after treatment. On very rare occasions, treatments other than Paxlovid are needed for people at high-risk for complications from COVID-19 who take certain medications.

How can I best protect myself from COVID-19?

Improvements in how COVID-19 is prevented and treated have led to a relative relaxation in guidance on how to avoid the virus. In early March, the CDC began to group its COVID-19 guidelines with other diseases caused by respiratory viruses such as flu and respiratory syncytial virus (RSV).

The basic guidelines around avoiding respiratory viruses include:

• Staying up to date on your immunizations
• Practicing good hygiene like proper handwashing or covering coughs
• Access cleaner air by opening windows or gathering outdoors

If you get sick with a respiratory virus, it's best to stay home and away from others.

More information: Kristen Hansen et al, Paxlovid (nirmatrelvir/ritonavir) effectiveness against hospitalization and death in N3C: A target trial emulation study, medRxiv (2023). DOI: 10.1101/2023.05.26.23290602

Carlos K. H. Wong et al, Optimal timing of nirmatrelvir/ritonavir treatment after COVID-19 symptom onset or diagnosis: target trial emulation, Nature Communications (2023). DOI: 10.1038/s41467-023-43706-0

Provided by University of Kentucky

Do you need a spring COVID-19 vaccine? Research backs extra round for high-risk groups

Recent studies suggest staying up-to-date on covid shots helps protect high-risk groups from severe illness.

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New guidelines suggest certain high-risk groups could benefit from having another dose of a COVID-19 vaccine this spring — and more frequent shots in general — while the broader population could be entering once-a-year territory, much like an annual flu shot.

Medical experts told CBC News that falling behind on the latest shots can come with health risks, particularly for individuals who are older or immunocompromised.

"Even when the risk of infection starts to increase, the vaccines still do a really good job at decreasing risk of severe disease," said McMaster University researcher and immunologist Matthew Miller.

Who needs another COVID shot?

Back in January, Canada's national vaccine advisory body set the stage for another round of spring vaccinations. In a statement , the National Advisory Committee on Immunization (NACI) stated that starting in spring 2024, individuals at an increased risk of severe COVID may get an extra dose of the latest XBB.1.5-based vaccines, which better protect against circulating virus variants.

That means:

• Adults aged 65 and up.
• Adult residents of long-term care homes and other congregate living settings for seniors.
• Anyone six months of age or older who is moderately to severely immunocompromised.

The various spring recommendations don't focus on pregnancy, despite research showing clear links between a COVID infection while pregnant, and increased health risks. However, federal guidance does note that getting vaccinated during pregnancy can protect against serious outcomes.

"Vaccinated people can also pass antibodies to their baby through the placenta and through breastmilk," that guidance states .

What do the provinces now recommend?

Multiple provinces have started rolling out their own regional guidance based on those early recommendations — with a focus on allowing similar high-risk groups to get another round of vaccinations.

B.C. is set to announce guidance on spring COVID vaccines in early April, officials told CBC News, and those recommendations are expected to align with NACI's guidance. 

In Manitoba , high-risk individuals are already eligible for another dose, provided it's been at least three months since their latest COVID vaccine.

• Older P.E.I. residents, others at risk, urged to get spring COVID vaccine booster
• High-risk groups can now book spring COVID-19 vaccination in Nova Scotia

Meanwhile Ontario's latest guidance , released on March 21, stresses that high-risk individuals may get an extra dose during a vaccine campaign set to run between April and June. Eligibility will involve waiting six months after someone's last dose or COVID infection.

Having a spring dose "is particularly important for individuals at increased risk of severe illness from COVID-19 who did not receive a dose during the Fall 2023 program," the guidance notes. 

And in Nova Scotia , the spring campaign will run from March 25 to May 31, also allowing high-risk individuals to get another dose.

Specific eligibility criteria vary slightly from province-to-province, so Canadians should check with their primary care provider, pharmacist or local public health team for exact guidelines in each area.

Age still best determines when to get COVID vaccines, new research suggests

Why do the guidelines focus so much on age.

The rationale behind the latest spring guidelines, Miller said, is that someone's age remains one of the greatest risk factors associated with severe COVID outcomes, including hospitalization, intensive care admission and death. 

"So that risk starts to shoot up at about 50, but really takes off in individuals over the age of 75," he noted.

Canadian data suggests the overwhelming majority of COVID deaths have been among older adults, with nearly 60 per cent of deaths among those aged 80 or older, and roughly 20 per cent among those aged 70 to 79.

People with compromised immune systems or serious medical conditions are also more vulnerable, Miller added.

Will people always need regular COVID shots?

While the general population may not require shots as frequently as higher-risk groups, Miller said it's unlikely there will be recommendations any time soon to have a COVID shot less than once a year, given ongoing uncertainty about COVID's trajectory.

"Going forward, I suspect for pragmatic reasons, [COVID vaccinations] will dovetail with seasonal flu vaccine campaigns, just because it makes the implementation much more straightforward," Miller said.

• Just 15% of Canadians got updated COVID vaccines this fall, new figures show
• Spring COVID-19 vaccines available April 2 in N.B. for those at high-risk

"And although we haven't seen really strong seasonal trends with SARS-CoV-2 now, I suspect we'll get to a place where it's more seasonal than it has been."

In the meantime, the guidance around COVID shots remains simple at its core: Whenever you're eligible to get another dose — whether that's once or twice a year — you might as well do it.

What does research say?

One analysis, published in early March in the medical journal Lancet Infectious Diseases , studied more than 27,000 U.S. patients who tested positive for SARS-CoV-2, the virus behind COVID, between September and December 2023. 

The team found individuals who had an updated vaccine reduced their risk of severe illness by close to a third — and the difference was more noticeable in older and immunocompromised individuals.

Another American research team from Stanford University recently shared the results from a modelling simulation looking at the ideal frequency for COVID vaccines. 

• Elderly Canadians remain at higher risk of serious COVID from first infections, study suggests
• Spring vaccine dose suggested to protect seniors in Canada from severe COVID

The study in Nature Communications suggests that for individuals aged 75 and up, having an annual COVID shot could reduce severe infections from an estimated 1,400 cases per 100,000 people to around 1,200 cases — while bumping to twice a year could cut those cases even further, down to 1,000.

For younger, healthier populations, however, the benefit of regular shots against severe illness was more modest.

The outcome wasn't a surprise to Stanford researcher Dr. Nathan Lo, an infectious diseases specialist, since old age has consistently been a risk factor for severe COVID.

"It's almost the same pattern that's been present the entire pandemic," he said. "And I think that's quite striking."

More frequent vaccination won't prevent all serious infections, he added, or perhaps even a majority of those infections, which highlights the need for ongoing mitigation efforts.

ABOUT THE AUTHOR

Senior Health & Medical Reporter

Lauren Pelley covers health and medical science for CBC News, including the global spread of infectious diseases, Canadian health policy, pandemic preparedness, and the crucial intersection between human health and climate change. Two-time RNAO Media Award winner for in-depth health reporting in 2020 and 2022. Contact her at: [email protected]

• @LaurenPelley

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Opinion: How should we deal with COVID now?

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This month, the Centers for Disease Control and Prevention released new COVID guidelines ending the five-day isolation recommendation . The agency now advises staying home only if you have symptoms, such as fever. Otherwise, you can return “to normal activities ” if, for at least 24 hours, your symptoms are improving overall and any fever has gone away without the use of fever-reducing medication. The official announcement follows unconfirmed reports in February of this change.

As is often the case with COVID-19, the news has started a back-and-forth as to whether the latest government rules are too strict or too loose. Our approach to the virus as endemic remains uneasy as the annual death toll, estimated at below 70,000 in 2023, drops closer to but remains significantly higher than the toll of the flu .

Some experts have questioned the policy shift, since there is no new science strongly defining COVID’s contagious period by an active fever. Others have supported the agency’s goal of making COVID-19 guidelines “ easy to understand ” and follow, aligning them with recommendations for other seasonal viruses. Many, including me, want to see flexibility for high-risk environments such as hospitals and nursing homes to implement more conservative guidelines, with longer isolation periods and lower thresholds for staying at home.

But these conversations dodge many of the realities of COVID-19 in this phase. While we continue to debate ways to shape individual human behavior for collective protection, we’re squandering some of the resources we’ve already put toward fighting this disease.

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Vaccination got us past the worst of the pandemic, yet now we’re under-using it to control COVID-19 and, more importantly, reduce deaths. In the United States, immunization rates for the recommended boosters remain low even in high-risk groups, such as older adults and the immunocompromised. As of early March, the rate among those 60 years or older was 42% (and just 23% for all adults eligible for the latest version of the vaccine).

The reasons for this extend well beyond the often-blamed mistrust in science. For one thing, we’re missing opportunities to vaccinate people who might not on their own pursue a shot. Inoculation should be easily available to those who show up at health facilities for whatever reason — testing, routine care, emergencies — and would be open to being vaccinated then. There are also people who could still be persuaded into getting boosters. Doctors, nurses and other healthcare providers remain the most trusted sources of vaccine information. A strong recommendation from a provider makes it more likely that a patient will get a vaccine.

Counseling patients about vaccines requires providers’ time. The Centers for Medicare & Medicaid Services reimburses physicians if they counsel certain patients, or their caregivers, about receiving a recommended vaccine even if the patient declines the vaccine that day. This provision covers beneficiaries of Medicaid and the Children’s Health Insurance Program. But for most other insurers, vaccination costs are reimbursed only if a patient ends up getting vaccinated, which providers won’t know before giving counsel. Not consistently making vaccine counseling reimbursable, unlike, say, nutritional counseling, disincentivizes healthcare providers to spend the time needed.

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The chaos of healthcare expenses creates further obstacles. The U.S. reimbursement system is primarily designed for treatment, not prevention. After the federal government stopped directly covering the cost of the vaccine , it fell to the patchwork of largely insurance-based payers. People have found it hard to navigate the new payment process.

Another payment problem arises around antiviral medications such as Paxlovid — imperfect but useful tools to reduce death among those infected with the SARS-CoV-2 virus. The drugs are most useful if administered soon after infection, and Pfizer set the out-of-pocket price for a five-day course at $1,390 . After the COVID-19 public health emergency ended, the Department of Health and Human Services reached an agreement with Pfizer to increase access through the Paxcess program, which ensures that the drug is free for those on Medicaid and Medicare and the underinsured. There’s also a copay assistance program for others who cannot afford the drug.

Unfortunately many people, including pharmacists, are not aware of this program. Access to a mortality-reducing drug should not be a well-kept secret. The Department of Health and Human Services should embark on an expanded pharmacist and healthcare provider information initiative, working with all major pharmacy chains, to add electronic prompts for Paxcess to prescription fulfillment systems.

Another underused COVID resource: improved indoor ventilation and air filtration. These interventions include increasing indoor airflow through mechanical means (such as modification to HVAC systems) or natural means (such as keeping the windows open); proper filtration of circulating air through air cleaners or through heating, ventilation and air conditioning; and installing ultraviolet irradiation equipment to kill viruses.

Fortunately, there is federal funding available for locations with high population density, including schools , to improve indoor air quality. But far too few have since upgraded their ventilation and air filtration systems. More use of that funding, alongside support from the private sector, could make buildings healthier.

These meat-and-potatoes approaches — vaccination, access to treatment and clean air — may not be the most exciting tools. But they reflect the best of public health: strategies that are so effective they almost invisibly reduce life-threatening illness.

Saad B. Omer is an epidemiologist and vaccine expert.

More to Read

U.S. health officials drop 5-day isolation time for COVID-19

March 1, 2024

In a milestone, California says those with COVID-19 can leave home sooner — but there’s a catch

Jan. 29, 2024

California relaxes COVID isolation guidance. What you need to know

Jan. 25, 2024

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