sample research title about covid 19

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100+ Best Research Titles About COVID-19 Examples

The covid-19 pandemic has been the most devastating thing to happen in humanity in the past decade or two. It caused global panic and changed people’s lives in multiple aspects. Therefore, it is the perfect research topic for high school, postgraduate, and undergraduate students.

Exciting Sample Research Title About Pandemic

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Academic research related to covid-19 would be perfect because of its relevance. Furthermore, it applies to any field of study thanks to the vast and immense impacts of the pandemic. For instance, business and finance students can research the effects of the covid-19 pandemic on the economy, while social science majors can discuss the various social results.

The pandemic research topics are a good path also because they are interesting. Additionally, research topic examples about covid-19 give you a great research opportunity because of the numerous materials. There are multiple topics you can consider, from the quantitative and qualitative research titles about covid 19 to the effects and reception of the vaccine, among others.

Ready for detailed quantitative and qualitative research topics ? Find a great research title about a covid-19 example from the samples below.

The impacts of the pandemic were and are still felt globally. So, this means that there are numerous creative directions you can pursue when choosing the perfect topic. Here are some research titles about the pandemic and argumentative essay topics :

• An exploration of the impacts of the pandemic on the global economy
• The covid-19 pandemic and the global recession: what is the link?
• The correlation between your country’s economy and its response to the pandemic
• The connection between kid’s immune system and their survival from the pandemic
• The impacts of the pandemic on third world countries
• A comparison of the effects of the pandemic on third and first-world countries
• A comparison of the response to the pandemic in Europe and America
• The role of the pandemic in the appreciation of the scientific research field
• An exploration of the long-term impacts of the pandemic on the education sector?
• What could global governments have done better to prevent the pandemic?

Quantitative research about the pandemic involves collecting and analyzing data. However, choosing a quantitative research topic is not easy since you must select a researchable one. An example of a quantitative research title about covid-19 may be a good start. So, let’s look at some quantitative research title examples about covid-19:

• How effective are detergents against germs during the pandemic?
• An exploration of coronavirus response and future preparedness against pandemics
• The global coronavirus pandemic: prevention and transmission of the virus
• A look into the ethical controversies during the pandemic
• A look into the effectiveness of the pandemic regulations
• The psychological effects of the pandemic’s control measures
• A link between intimate partner violence increase and the pandemic
• Impacts of the global pandemic on the sports sector
• The influences of the coronavirus pandemic on human relations
• The pandemic and its aftermath

A qualitative research title about covid-19 significantly depends on data collected from first-hand observations, interviews, recordings in natural settings, and case studies. So, qualitative social issues research topics are mostly non-numerical data. Find a qualitative research title about the pandemic from the samples below:

• How ethical are the covid-19 regulations?
• The rise of racist attacks during the coronavirus pandemic
• Racist attacks against the Asian community: what role did covid-19 pandemic play in this?
• Hoarding and selfish tendencies during the coronavirus pandemic
• The rise of the internet age during the coronavirus pandemic
• How streaming services have benefited from the covid-19 pandemic
• The role of pandemics and epidemics in promoting global change
• The rate of employee retention among local businesses during the covid-19 pandemic
• Companies that saw significant profits during the pandemic
• Controversial theories about the pandemic and the coronavirus

You can also find a quantitative research title about covid-19, specifically focusing on the pandemic and its resulting issues. In addition to a quantitative research topic during a pandemic, research topics for STEM students are also pretty interesting. Here are some research topics during the pandemic that you can write about:

• A link between the pandemic and employee retention rates in large corporations
• Global recovery from the pandemic
• The profoundly detrimental consequences of the covid-19 pandemic on the economy
• How the global economy can recover from the pandemic
• The long-term effects of the pandemic on the medical sector
• The correlation between a decrease in employees in the medical industry and the pandemic
• Mitigating the detrimental impacts of the pandemic on the education sector
• The link between the pandemic and increased mental health challenges
• The pandemic and depression: what is the link?
• An analysis of the death rates during the life cycle of the coronavirus pandemic

You can also explore various research topics related to the covid-19 vaccines. The vaccine has been a controversial topic to study from various angles. Here are some research topics about covid 19, especially about vaccines:

• The difference between the acceptance of the covid-19 vaccine in first and third-world countries
• The role of social media influencers in promoting covid-19 vaccines
• The controversies surrounding the covid-19 vaccine
• How effective is the covid-19 vaccines against the virus?
• An analysis of the covid-19 vaccination rates among conservative Americans?
• The adverse effects of the covid-19 vaccine
• An overview of the pros and cons of the covid-19 vaccines
• The rate of covid-19 vaccination in 2021 vs. 2022
• Covid-19 vaccine boosters: how many people go for the booster shots?
• What happens when you get covid-19 after the vaccination?

When choosing a research topic, always pick an interesting and relevant topic. Doing so will simplify your research, help with data collection, and make your paper enjoyable. Get a research title about covid 19 quantitative for 2020 from the list below:

• An analysis of the start of the covid-19 pandemic
• An overview of the source of the coronavirus
• Breaking down the myths about the coronavirus, its inception, and its impacts
• The link between the spike in opioid addiction and the pandemic
• The effects of the pandemic on essential social values
• Quarantine in third-world countries compared to first-world countries
• The rates of covid-19 infections and deaths in Africa
• Social barriers during and after the coronavirus pandemic
• Consumer Psychonomic during the covid-19 pandemic
• The impact of the covid-19 pandemic on a globalized economy

The covid-19 pandemic offers multiple incredible research topic ideas. Choosing the best research title about the coronavirus can be tricky. So, let’s look at some qualitative research title examples about covid-19:

• The covid-19 pandemic and what we can learn from it
• What can global governments take away from the covid-19 pandemic?
• An exploration of the impact of the coronavirus on the body
• A look at how a strong immune system fights the coronavirus
• Mental well-being during the coronavirus pandemic
• Covid-19: managerial accounting during the pandemic
• The positive impacts of the pandemic on the environment
• A compelling city planning approach during the pandemic
• Covid-19 and social values: what is the link
• American administration responses to the covid-19 pandemic

The pandemic is a great study area for a thesis. You can choose various directions for your thesis depending on your study area and interest. Whether it is a quantitative research title about the pandemic or an example of a qualitative research title about covid-19, the following research titles about covid 19 should come in handy:

• The coronavirus pandemic: changes in public spaces and hygiene
• Development Control Regulations as the perfect medium to navigate and fight the pandemic
• A revision of housing topologies after the pandemic
• The drastic effects of the pandemic on the public transformation system
• Workspace design changes after the pandemic
• The effects of the pandemic on productivity and company culture
• The concept of social distancing during the pandemic and its effectiveness
• Sanitization practices in public spaces and residential buildings during the pandemic
• Pedestrianization during the coronavirus pandemic
• Public transportation and its impacts during the covid-19 pandemic

The covid-19 pandemic affected multiple sectors. However, the business industry is arguably the most impacted area beside the medical sector. So, a research title about business during the pandemic is an excellent study focus. Find a research title for the pandemic specifically focused on business:

• The rate of business launches during the pandemic
• How online businesses benefited from the pandemic
• The pandemic and the business sector: the correlation
• An overview of successful companies launched during the pandemic
• The rate of business closures during the pandemic
• How did businesses survive the pandemic
• How Amazon took advantage of the pandemic to become a global giant
• Lessons businesses can take away from the pandemic and its impacts
• Business consumer retention and the pandemic
• Crisis preparedness: what businesses learned from the coronavirus pandemic

A research title about the pandemic can be a great idea if you want to study a relevant topic. However, the topic relevance will depend on your study area. Find a great topic for research this pandemic from the list below:

• A comprehensive reflection on the covid-19 pandemic
• Leadership and management during the coronavirus pandemic
• Economic factors and consequences of the covid-19 pandemic
• Religion and the coronavirus pandemic: what is the overview?
• The role of social media in spreading misinformation on the covid-19 pandemic
• The role of social media in promoting the covid-19 pandemic
• How streaming services and the internet helped maintain peoples’ sanity in the pandemic
• Misinformation handling during the coronavirus pandemic
• Job satisfaction levels during the pandemic in 2020 and 2021
• A controversial argument on the benefits of the pandemic

A research title about the vaccine of covid 19 can be controversial. However, it makes an excellent topic for intellectual study. Find the best title for research about the pandemic related to vaccines

• Mental health during the coronavirus pandemic and what to improve
• Conspiracy theories regarding the covid-19 pandemic
• Conservative views on the covid-19 vaccine in the Christian community
• Public health: the issue of the coronavirus pandemic between 2020 to 2022
• The changing health behaviors following the coronavirus pandemic situation
• The impacts of the pandemic on early childhood development the pandemic
• The pandemic generation: children born during the pandemic and their view of the world
• A comparison of the influenza pandemic and the covid-19 pandemic
• The effect of the pandemic on workers in the medical sector
• Stress and coping mechanisms for nurses and doctors during the covid-19 sector

You can find a thesis statement about social media or a great research title about covid 19 vaccine and other topics online. However, not every research title about covid is relevant or great for academic research. You need the best social media research topics . Find a fantastic title of research about covid from the list below:

• How social media helped mitigate the impacts of the pandemic
• The rise of TikTok during the pandemic
• Social media influence during the pandemic and the changes
• The positive changes in the view of the coronavirus pandemic on social media tendencies
• School closure during the coronavirus pandemic and the role of social media
• The role of social media in promoting mental well-being during the covid-19 pandemic
• Streaming services for the elderly during the 2020 coronavirus pandemic
• How did the pandemic lead to increased adverse effects of social media
• The American mental health population: the impacts of the covid-19 pandemic
• Business negotiation strategies during the covid-19 pandemic

Third-world countries like the Philippines are among the most impacted nations by the pandemic. So, cover the research title example quantitative or qualitative, depending on your preferred data collection and analysis techniques. Some pandemic research title examples about the Philippines are:

• The Philippines’ medical sector during the pandemic
• Mitigation measures by the Philippines government during the pandemic
• How the pandemic impacted the Philippines’ public sector
• The Philippines’ education sector after the pandemic
• Religion and the covid-19 pandemic: God’s existence in Covid-19 times
• Philippines’ public policies after the pandemic
• The Philippines food and beverage plan: the impacts of the pandemic
• Covid-19 vaccination rates in the Philippines’
• The psychological impacts of the pandemic on the Philippines society
• A survey on conditions of low-income households during the pandemic

Title research about the pandemic will earn you excellent grades because of the topic’s relevance and multiple study opportunities. However, the quality of the subject matters significantly. Find an example of a research title about covid-19 pandemic below:

• What has the world learned from the covid-19 pandemic?
• How has the pandemic influenced the public’s view of health?
• Why are there fewer medical employees after the pandemic?
• How did nurses and doctors survive overworking during the pandemic?
• Is there a link between the global recession and the pandemic?
• How did the WHO’s response to the pandemic help mitigate its impacts?
• What challenges did the WHO face while addressing the covid-19 pandemic?
• Should people continue getting covid-19 vaccinations in 2022?
• What is the correlation between the pandemic and the current state of global society?
• What is social solidarity during the pandemic?

The covid-19 pandemic front liners were among the most impacted by the pandemic. So, it would make sense to focus your study on the frontliners. Find an incredible sample of a research title during the pandemic here:

• Frontliners during the pandemic: how were they affected?
• An overview of front liner’s view of the pandemic
• A look into the covid-19 pandemic through the eyes of the pandemic
• School closures during the pandemic: the impacts on frontline families
• Effects of the pandemic on social relationships among frontliners
• Frontliners: how their families suffered from the pandemic
• Frontliner mental health and the pandemic: the correlation
• Getting back into conventional practices in the medical sector after the pandemic
• How frontline helped mitigate the risks of the pandemic
• The age of online learning before and after the pandemic

You do not have to be in college or university to focus your research on the pandemic. Even high school students can write research topics about the pandemic. Here are some sample research topics for high school students:

• Organizational risk management strategies after the pandemic
• Social solidarity and the pandemic: the link
• A link between the social response to plagues and the covid-19 pandemic
• Social changes after the covid-19 pandemic
• The covid-19 pandemic and the World History
• Healthcare management and quality during the covid-19 pandemic
• The covid-19 pandemic: The story of the 21 st -century pandemic
• Child abuse and the pandemic: a correlation
• The covid-19 pandemic: causes and solutions
• The reality of the covid-19 pandemic in the elder community

Reach Out for More Interesting Topics About the Covid-19 Pandemic

You deserve the best research titles for high school, postgraduate, and undergraduate studies. Now that you know the best research title about covid-19 to choose from, reach out to us for help with COVID-19 assignments, research papers, essays, thesis for bachelor degree and even more topic suggestions in this area.

Scientists now agree that the COVID pandemic is arguably the most annoying thing to happen in the 21 st century, making it an ideal focus area. It will go down in history as the most challenging time for the economy, environment, and human health.

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• Research article
• Open access
• Published: 04 June 2021

Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews

• Israel Júnior Borges do Nascimento 1 , 2 ,
• Dónal P. O’Mathúna 3 , 4 ,
• Thilo Caspar von Groote 5 ,
• Hebatullah Mohamed Abdulazeem 6 ,
• Ishanka Weerasekara 7 , 8 ,
• Ana Marusic 9 ,
• Livia Puljak   ORCID: orcid.org/0000-0002-8467-6061 10 ,
• Vinicius Tassoni Civile 11 ,
• Irena Zakarija-Grkovic 9 ,
• Tina Poklepovic Pericic 9 ,
• Alvaro Nagib Atallah 11 ,
• Santino Filoso 12 ,
• Nicola Luigi Bragazzi 13 &
• Milena Soriano Marcolino 1

On behalf of the International Network of Coronavirus Disease 2019 (InterNetCOVID-19)

BMC Infectious Diseases volume  21 , Article number:  525 ( 2021 ) Cite this article

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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.

This research received no external funding.

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University Hospital and School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

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

Department of Physiotherapy, Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka

Cochrane Croatia, University of Split, School of Medicine, Split, Croatia

Ana Marusic, Irena Zakarija-Grkovic & Tina Poklepovic Pericic

Center for Evidence-Based Medicine and Health Care, Catholic University of Croatia, Ilica 242, 10000, Zagreb, Croatia

Livia Puljak

Cochrane Brazil, Evidence-Based Health Program, Universidade Federal de São Paulo, São Paulo, Brazil

Vinicius Tassoni Civile & Alvaro Nagib Atallah

Yorkville University, Fredericton, New Brunswick, Canada

Santino Filoso

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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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The Impact of COVID-19 on the Careers of Women in Academic Sciences, Engineering, and Medicine (2021)

Chapter: 8 major findings and research questions, 8 major findings and research questions, introduction.

The COVID-19 pandemic, which began in late 2019, created unprecedented global disruption and infused a significant level of uncertainty into the lives of individuals, both personally and professionally, around the world throughout 2020. The significant effect on vulnerable populations, such as essential workers and the elderly, is well documented, as is the devastating effect the COVID-19 pandemic had on the economy, particularly brick-and-mortar retail and hospitality and food services. Concurrently, the deaths of unarmed Black people at the hands of law enforcement officers created a heightened awareness of the persistence of structural injustices in U.S. society.

Against the backdrop of this public health crisis, economic upheaval, and amplified social consciousness, an ad hoc committee was appointed to review the potential effects of the COVID-19 pandemic on women in academic science, technology, engineering, mathematics, and medicine (STEMM) during 2020. The committee’s work built on the National Academies of Sciences, Engineering, and Medicine report Promising Practices for Addressing the Underrepresentation of Women in Science, Engineering, and Medicine: Opening Doors (the Promising Practices report), which presents evidence-based recommendations to address the well-established structural barriers that impede the advancement of women in STEMM. However, the committee recognized that none of the actions identified in the Promising Practices report were conceived within the context of a pandemic, an economic downturn, or the emergence of national protests against structural racism. The representation and vitality of academic women in STEMM had already warranted national attention prior to these events, and the COVID-19

pandemic appeared to represent an additional risk to the fragile progress that women had made in some STEMM disciplines. Furthermore, the future will almost certainly hold additional, unforeseen disruptions, which underscores the importance of the committee’s work.

In times of stress, there is a risk that the divide will deepen between those who already have advantages and those who do not. In academia, senior and tenured academics are more likely to have an established reputation, a stable salary commitment, and power within the academic system. They are more likely, before the COVID-19 pandemic began, to have established professional networks, generated data that can be used to write papers, and achieved financial and job security. While those who have these advantages may benefit from a level of stability relative to others during stressful times, those who were previously systemically disadvantaged are more likely to experience additional strain and instability.

As this report has documented, during 2020 the COVID-19 pandemic had overall negative effects on women in academic STEMM in areas such productivity, boundary setting and boundary control, networking and community building, burnout rates, and mental well-being. The excessive expectations of caregiving that often fall on the shoulders of women cut across career timeline and rank (e.g., graduate student, postdoctoral scholar, non-tenure-track and other contingent faculty, tenure-track faculty), institution type, and scientific discipline. Although there have been opportunities for innovation and some potential shifts in expectations, increased caregiving demands associated with the COVID-19 pandemic in 2020, such as remote working, school closures, and childcare and eldercare, had disproportionately negative outcomes for women.

The effects of the COVID-19 pandemic on women in STEMM during 2020 are understood better through an intentionally intersectional lens. Productivity, career, boundary setting, mental well-being, and health are all influenced by the ways in which social identities are defined and cultivated within social and power structures. Race and ethnicity, sexual orientation, gender identity, academic career stage, appointment type, institution type, age, and disability status, among many other factors, can amplify or diminish the effects of the COVID-19 pandemic for a given person. For example, non-cisgender women may be forced to return to home environments where their gender identity is not accepted, increasing their stress and isolation, and decreasing their well-being. Women of Color had a higher likelihood of facing a COVID-19–related death in their family compared with their white, non-Hispanic colleagues. The full extent of the effects of the COVID-19 pandemic for women of various social identities was not fully understood at the end of 2020.

Considering the relative paucity of women in many STEMM fields prior to the COVID-19 pandemic, women are more likely to experience academic isolation, including limited access to mentors, sponsors, and role models that share gender, racial, or ethnic identities. Combining this reality with the physical isolation stipulated by public health responses to the COVID-19 pandemic,

women in STEMM were subject to increasing isolation within their fields, networks, and communities. Explicit attention to the early indicators of how the COVID-19 pandemic affected women in academic STEMM careers during 2020, as well as attention to crisis responses throughout history, may provide opportunities to mitigate some of the long-term effects and potentially develop a more resilient and equitable academic STEMM system.

MAJOR FINDINGS

Given the ongoing nature of the COVID-19 pandemic, it was not possible to fully understand the entirety of the short- or long-term implications of this global disruption on the careers of women in academic STEMM. Having gathered preliminary data and evidence available in 2020, the committee found that significant changes to women’s work-life boundaries and divisions of labor, careers, productivity, advancement, mentoring and networking relationships, and mental health and well-being have been observed. The following findings represent those aspects that the committee agreed have been substantiated by the preliminary data, evidence, and information gathered by the end of 2020. They are presented either as Established Research and Experiences from Previous Events or Impacts of the COVID-19 Pandemic during 2020 that parallel the topics as presented in the report.

Established Research and Experiences from Previous Events

___________________

1 This finding is primarily based on research on cisgender women and men.

Impacts of the COVID-19 Pandemic during 2020

Research questions.

While this report compiled much of the research, data, and evidence available in 2020 on the effects of the COVID-19 pandemic, future research is still needed to understand all the potential effects, especially any long-term implications. The research questions represent areas the committee identified for future research, rather than specific recommendations. They are presented in six categories that parallel the chapters of the report: Cross-Cutting Themes; Academic Productivity and Institutional Responses; Work-Life Boundaries and Gendered Divisions of Labor; Collaboration, Networking, and Professional Societies; Academic Leadership and Decision-Making; and Mental Health and Well-being. The committee hopes the report will be used as a basis for continued understanding of the impact of the COVID-19 pandemic in its entirety and as a reference for mitigating impacts of future disruptions that affect women in academic STEMM. The committee also hopes that these research questions may enable academic STEMM to emerge from the pandemic era a stronger, more equitable place for women. Therefore, the committee identifies two types of research questions in each category; listed first are those questions aimed at understanding the impacts of the disruptions from the COVID-19 pandemic, followed by those questions exploring the opportunities to help support the full participation of women in the future.

Cross-Cutting Themes

• What are the short- and long-term effects of the COVID-19 pandemic on the career trajectories, job stability, and leadership roles of women, particularly of Black women and other Women of Color? How do these effects vary across institutional characteristics, 2 discipline, and career stage?

2 Institutional characteristics include different institutional types (e.g., research university, liberal arts college, community college), locales (e.g., urban, rural), missions (e.g., Historically Black Colleges and Universities, Hispanic-Serving Institutions, Asian American/Native American/Pacific Islander-Serving Institutions, Tribal Colleges and Universities), and levels of resources.

• How did the confluence of structural racism, economic hardships, and environmental disruptions affect Women of Color during the COVID-19 pandemic? Specifically, how did the murder of George Floyd, Breonna Taylor, and other Black citizens impact Black women academics’ safety, ability to be productive, and mental health?
• How has the inclusion of women in leadership and other roles in the academy influenced the ability of institutions to respond to the confluence of major social crises during the COVID-19 pandemic?
• How can institutions build on the involvement women had across STEMM disciplines during the COVID-19 pandemic to increase the participation of women in STEMM and/or elevate and support women in their current STEMM-related positions?
• How can institutions adapt, leverage, and learn from approaches developed during 2020 to attend to challenges experienced by Women of Color in STEMM in the future?

Academic Productivity and Institutional Responses

• How did the institutional responses (e.g., policies, practices) that were outlined in the Major Findings impact women faculty across institutional characteristics and disciplines?
• What are the short- and long-term effects of faculty evaluation practices and extension policies implemented during the COVID-19 pandemic on the productivity and career trajectories of members of the academic STEMM workforce by gender?
• What adaptations did women use during the transition to online and hybrid teaching modes? How did these techniques and adaptations vary as a function of career stage and institutional characteristics?
• What are examples of institutional changes implemented in response to the COVID-19 pandemic that have the potential to reduce systemic barriers to participation and advancement that have historically been faced by academic women in STEMM, specifically Women of Color and other marginalized women in STEMM? How might positive institutional responses be leveraged to create a more resilient and responsive higher education ecosystem?
• How can or should funding arrangements be altered (e.g., changes in funding for research and/or mentorship programs) to support new ways of interaction for women in STEMM during times of disruption, such as the COVID-19 pandemic?

Work-Life Boundaries and Gendered Divisions of Labor

• How do different social identities (e.g., racial; socioeconomic status; culturally, ethnically, sexually, or gender diverse; immigration status; parents of young children and other caregivers; women without partners) influence the management of work-nonwork boundaries? How did this change during the COVID-19 pandemic?
• How have COVID-19 pandemic-related disruptions affected progress toward reducing the gender gap in academic STEMM labor-force participation? How does this differ for Women of Color or women with caregiving responsibilities?
• How can institutions account for the unique challenges of women faculty with parenthood and caregiving responsibilities when developing effective and equitable policies, practices, or programs?
• How might insights gained about work-life boundaries during the COVID-19 pandemic inform how institutions develop and implement supportive resources (e.g., reductions in workload, on-site childcare, flexible working options)?

Collaboration, Networking, and Professional Societies

• What were the short- and long-term effects of the COVID-19 pandemic-prompted switch from in-person conferences to virtual conferences on conference culture and climate, especially for women in STEMM?
• How will the increase in virtual conferences specifically affect women’s advancement and career trajectories? How will it affect women’s collaborations?
• How has the shift away from attending conferences and in-person networking changed longer-term mentoring and sponsoring relationships, particularly in terms of gender dynamics?
• How can institutions maximize the benefits of digitization and the increased use of technology observed during the COVID-19 pandemic to continue supporting women, especially marginalized women, by increasing accessibility, collaborations, mentorship, and learning?
• How can organizations that support, host, or facilitate online and virtual conferences and networking events (1) ensure open and fair access to participants who face different funding and time constraints; (2) foster virtual connections among peers, mentors, and sponsors; and (3) maintain an inclusive environment to scientists of all backgrounds?
• What policies, practices, or programs can be developed to help women in STEMM maintain a sense of support, structure, and stability during and after periods of disruption?

Academic Leadership and Decision-Making

• What specific interventions did colleges and universities initiate or prioritize to ensure that women were included in decision-making processes during responses to the COVID-19 pandemic?
• How effective were colleges and universities that prioritized equity-minded leadership, shared leadership, and crisis leadership styles at mitigating emerging and potential negative effects of the COVID-19 pandemic on women in their communities?
• What specific aspects of different leadership models translated to more effective strategies to advance women in STEMM, particularly during the COVID-19 pandemic?
• How can examples of intentional inclusion of women in decision-making processes during the COVID-19 pandemic be leveraged to develop the engagement of women as leaders at all levels of academic institutions?
• What are potential “top-down” structural changes in academia that can be implemented to mitigate the adverse effects of the COVID-19 pandemic or other disruptions?
• How can academic leadership, at all levels, more effectively support the mental health needs of women in STEMM?

Mental Health and Well-being

• What is the impact of the COVID-19 pandemic and institutional responses on the mental health and well-being of members of the academic STEMM workforce as a function of gender, race, and career stage?
• How are tools and diagnostic tests to measure aspects of wellbeing, including burnout and insomnia, used in academic settings? How does this change during times of increased stress, such as the COVID-19 pandemic?
• How might insights gained about mental health during the COVID-19 pandemic be used to inform preparedness for future disruptions?
• How can programs that focus on changes in biomarkers of stress and mood dysregulation, such as levels of sleep, activity, and texting patterns, be developed and implemented to better engage women in addressing their mental health?
• What are effective interventions to address the health of women academics in STEMM that specifically account for the effects of stress on women? What are effective interventions to mitigate the excessive levels of stress for Women of Color?

This page intentionally left blank.

The spring of 2020 marked a change in how almost everyone conducted their personal and professional lives, both within science, technology, engineering, mathematics, and medicine (STEMM) and beyond. The COVID-19 pandemic disrupted global scientific conferences and individual laboratories and required people to find space in their homes from which to work. It blurred the boundaries between work and non-work, infusing ambiguity into everyday activities. While adaptations that allowed people to connect became more common, the evidence available at the end of 2020 suggests that the disruptions caused by the COVID-19 pandemic endangered the engagement, experience, and retention of women in academic STEMM, and may roll back some of the achievement gains made by women in the academy to date.

The Impact of COVID-19 on the Careers of Women in Academic Sciences, Engineering, and Medicine identifies, names, and documents how the COVID-19 pandemic disrupted the careers of women in academic STEMM during the initial 9-month period since March 2020 and considers how these disruptions - both positive and negative - might shape future progress for women. This publication builds on the 2020 report Promising Practices for Addressing the Underrepresentation of Women in Science, Engineering, and Medicine to develop a comprehensive understanding of the nuanced ways these disruptions have manifested. The Impact of COVID-19 on the Careers of Women in Academic Sciences, Engineering, and Medicine will inform the academic community as it emerges from the pandemic to mitigate any long-term negative consequences for the continued advancement of women in the academic STEMM workforce and build on the adaptations and opportunities that have emerged.

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Coronapod: The big COVID research papers of 2020

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Benjamin Thompson, Noah Baker and Traci Watson discuss some of 2020's most significant coronavirus research papers.

In the final Coronapod of 2020, we dive into the scientific literature to reflect on the COVID-19 pandemic. Researchers have discovered so much about SARS-CoV-2 – information that has been vital for public health responses and the rapid development of effective vaccines. But we also look forward to 2021, and the critical questions that remain to be answered about the pandemic.

Papers discussed

A Novel Coronavirus from Patients with Pneumonia in China, 2019 - New England Journal of Medicine, 24 January

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China - The Lancet , 24 January

A pneumonia outbreak associated with a new coronavirus of probable bat origin - Nature , 3 February

A new coronavirus associated with human respiratory disease in China - Nature , 3 February

Temporal dynamics in viral shedding and transmissibility of COVID-19 - Nature Medicine , 15 April

Spread of SARS-CoV-2 in the Icelandic Population - New England Journal of Medicine , 11 June

High SARS-CoV-2 Attack Rate Following Exposure at a Choir Practice — Skagit County, Washington, March 2020 - Morbidity & Mortality Weekly Report , 15 August

Respiratory virus shedding in exhaled breath and efficacy of face masks - Nature Medicine , 3 April

Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1 - New England Journal of Medicine , 13 April

Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period - Science , 22 May

Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe - Nature, 8 June

The effect of large-scale anti-contagion policies on the COVID-19 pandemic - Nature , 8 June

Retraction—Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis - The Lancet, 20 June

A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 - New England Journal of Medicine , 3 June

Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19 - JAMA , 2 September

Immunological memory to SARS-CoV-2 assessed for greater than six months after infection - bioRxiv, 16 November

Coronavirus Disease 2019 (COVID-19) Re-infection by a Phylogenetically Distinct Severe Acute Respiratory Syndrome Coronavirus 2 Strain Confirmed by Whole Genome Sequencing - Clinical Infectious Diseases , 25 August

Nature’s COVID research updates – summarising key coronavirus papers as they appear

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Our COVID-19 Research Summary - 2021         

Related articles.

The published literature on COVID now exceeds 211,000 papers, books, and documents, which include: 22,866 observational studies, 19,591 reviews, 1496 meta-analyses and 781 randomized control trials. These publications comprise the backdrop for our research and writing. The project began in the spring of 2020 based on a limited source of cumulative COVID-19 data and has broadened considerably. Here is what we have learned.

Our objectives remain to

• Describe trends and the geographic extent of the pandemic, including associated predictors
• Evaluate the effectiveness of vaccinations and exposure limitations.
• Provide public health perspectives.

“We know that people’s behavior, the mode of transmission, and the virus‘s characteristics all play a role but we don’t have a clear quantitative understanding of how all of these forces interact. With COVID, the biggest wild card has been human behavior.”

Dr. R. Rosenfeld , Head, Department of Machine Learning, Carnegie Mellon

Our findings along with other COVID studies are observational , focusing on numbers rather than people. Since the annual COVID mortality rate is about is only about 1 in 700, achieving reliable statistics by state would require a cohort approaching a million subjects, each of which would have to be tracked over time in order to estimate exposures. Observational studies are thus the only practical option and uncertainties about causality vs. association are inevitable.

COVID-19 trends continue to defy analysis in large part because of unpredictable variants, the latest of which is still unfolding. However, some aspects remain and will continue to dominate:

• Daily cases, deaths, and incidence of long-haul COVID can be reduced more than 10-fold by vaccination, notwithstanding deterioration over time that requires boosting. 
• Acceptance of vaccination remains a personal choice - a choice that may be associated with personal characteristics including income, education, and political perspective.
• COVID-19 comprises a major cause of death in the United States and may continue to do so.

Findings In 2021 .

January . We showed that COVID-19 cases increased 10-fold, by 30% per month, during the 2020-21 winter; deaths generally followed suit, while case fatality rates (CFRs) decreased up to 10-fold. The Northeast region had shifted from worst to best, so that urban predictor variables like population density were no longer important. Regional rates coalesced in January.

February . The regional trend analyses showed declining cases but not deaths, with steady CFRs. We reported that “No plausible hypotheses have been advanced for the order-of-magnitude increases in cases and deaths since September”, now referred to as the “winter surge”. We compared urban and rural rates and noted the shift towards higher cases, deaths, and CFRs in rural areas.

March . We found that cases and deaths declined while CFRs increased 5-fold. Regional trends, which had ranged 4-fold for cases and deaths now coalesced. We analyzed short-term deaths and found a strong day-of-week effect, probably due to reporting error, but no evidence of important holiday surges.

April . We tried explaining the cyclical behavior of cases in terms of “susceptibles;” predicting an underlying trend of 5000 new cases per million per month. By contrast, the average case rate is now about 8000 cases per million per month - 53 million cases in total. However, after vaccinations got underway and prior to the Delta variant, new cases dropped to levels similar to those at the beginning of the pandemic. CFR’s ranged from about 0.015 in northern regions to 0.05 in the Southwest by April. We showed that Caucasian and mixed-race subjects had far lower COVID death rates than persons of color, and that COVID death rates increased with age at the same rate as non-COVID deaths.

May . COVID rates remained low in May. Comparing states, we reported significant relationships between COVID rates and political preference along with situational factors like household crowding. An increase in Republican voters of 60 percentage points, used as a marker of political perspective, was associated with a doubling of cumulative cases.

June . We revisited our previous consideration of airborne virus transmission, which had been espoused by CDC and the epidemiological community. We estimated ventilation rates and concluded that exposures in a small apartment were likely worse than in subways or aircraft. We also revisited urban-rural differences in more detail and showed that regional COVID rates had continued to coalesce.

July . We did a detailed analysis of vaccination rates and benefits. Daily vaccination rates peaked in April, at about 50% higher in the Northeast than elsewhere. We showed a strong significant decrease in daily state-level cases associated with full vaccination. We estimated unvaccinated case rates to be hundred-folds higher than with full vaccinations. We compared vaccination effects with education, and air pollution concluding that such personal characteristics could also be important. We also showed a negative state-level relationship between voting Republican and cumulative vaccination rates. Interestingly, vaccination rates correlated with COVID rates in 2020  before  mass vaccinations began, and vaccinations at this time, also apparently, reduced mortality not associated with COVID.  “ Could the decision to vaccinate have been more critical than the vaccination itself? ”

August . We reported that COVID case rates showed a sharp upturn, followed by death, likely due to the arrival of the Delta variant. Death rates and cases had decreased steadily until July to about 30 per million or 10,000 per day – a level the CDC considered as a “tolerable” endemic. We have not had these low levels since then. CFRs peaked in July, growing six-fold with substantial geographic variability.

September . We examined cyclical variations in daily infection rates and found substantial heterogeneity. State-level vaccination rates predicted both cases and death; and complete vaccination decreased case and death rates about 100-fold, even in the presence of the Delta variant.

October . We compared October’s COVID rates with those of the 2018-19 influenza to obtain a public health perspective. Total COVID-19 and influenza cases were similar at about 30 million and both were controlled by vaccination.  Compare to influenza, COVID hospitalizations were 4-fold higher and deaths were 20-fold higher - COVID is clearly the more serious disease. We concluded that 178,000 lives may have been saved by COVID-19 vaccination.

November . We continued examining vaccine effects and found no difference in the real-world effectiveness of Pfizer or Moderna vaccines. We found that COVID vaccinations were associated with reduced non-COVID deaths by 3-fold. We built an empirical mathematical model of the temporal variation of cases that fit the existing data very well but grossly underestimated the current situation. We predicted that full vaccinations for the U.S. might reach 72% in the next year, but with a range of 50-90% among states.

December . Cases began a sharp upward trend at years end, with deaths lagging behind. Regional gradients shifted, with Northwest highest and Northeast lowest. Vaccination rates continued to increase slowly, led by the Northeast. Previous beneficial effects of vaccination had been overshadowed by the severity of the Delta variant. We reported that vaccine effectiveness appears to decrease substantially over time. Long-haul COVID, neglected by the epidemiology community, was inversely associated with  vaccination rates and the socioeconomic factors underlying vaccine reluctance or refusal. We estimated trends and the contributions of immunity acquired from previous infection, which we found to be statistically modest.

View the discussion thread.

By Fred Lipfert, PhD

Latest from Fred Lipfert, PhD :

A Descriptive Study of COVID-19-Related Experiences and Perspectives of a National Sample of College Students in Spring 2020

Affiliations.

• 1 Department of Public and Nonprofit Administration, School of Management, University of San Francisco, San Francisco, California. Electronic address: [email protected].
• 2 Department of Psychology, Fordham University, New York, New York.
• PMID: 32593564
• PMCID: PMC7313499
• DOI: 10.1016/j.jadohealth.2020.06.009

Purpose: This is one of the first surveys of a USA-wide sample of full-time college students about their COVID-19-related experiences in spring 2020.

Methods: We surveyed 725 full-time college students aged 18-22 years recruited via Instagram promotions on April 25-30, 2020. We inquired about their COVID-19-related experiences and perspectives, documented opportunities for transmission, and assessed COVID-19's perceived impacts to date.

Results: Thirty-five percent of participants experienced any COVID-19-related symptoms from February to April 2020, but less than 5% of them got tested, and only 46% stayed home exclusively while experiencing symptoms. Almost all (95%) had sheltered in place/stayed primarily at home by late April 2020; 53% started sheltering in place before any state had an official stay-at-home order, and more than one-third started sheltering before any metropolitan area had an order. Participants were more stressed about COVID-19's health implications for their family and for American society than for themselves. Participants were open to continuing the restrictions in place in late April 2020 for an extended period of time to reduce pandemic spread.

Conclusions: There is substantial opportunity for improved public health responses to COVID-19 among college students, including for testing and contact tracing. In addition, because most participants restricted their behaviors before official stay-at-home orders went into effect, they may continue to restrict movement after stay-at-home orders are lifted, including when colleges reopen for in-person activities, if they decide it is not yet prudent to circulate freely. The public health, economic, and educational implications of COVID-19 are continuing to unfold; future studies must continue to monitor college student experiences and perspectives.

Keywords: COVID-19; College students; Epidemiology; Health behavior; Public health; USA.

Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

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SARS-CoV-2 and COVID-19: The most important research questions

Kit-san yuen.

1 School of Biomedical Sciences, The University of Hong Kong, 3/F Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong

2 Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong

Sin-Yee Fung

Chi-ping chan, dong-yan jin, associated data.

Not applicable.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Here we highlight nine most important research questions concerning virus transmission, asymptomatic and presymptomatic virus shedding, diagnosis, treatment, vaccine development, origin of virus and viral pathogenesis.

The 2019-nCoV causes an ongoing outbreak of lower respiratory tract disease called novel coronavirus pneumonia (NCP) by the Chinese government initially. The disease name was subsequently recommended as COVID-19 by the World Health Organization. Meanwhile, 2019-nCoV was renamed SARS-CoV-2 by the International Committee on Taxonomy of Viruses. As of February 24, 2020, more than 80,000 confirmed cases including more than 2,700 deaths have been reported worldwide, affecting at least 37 countries. The WHO has declared this a global health emergency at the end of January 2020. The epicenter of this ongoing outbreak is in the city of Wuhan in Hubei Province of central China and the Huanan seafood wholesale market was thought to be at least one of the places where SARS-CoV-2 from an unknown animal source might have crossed the species barrier to infect humans.

A pioneering study conducted in the city of Shenzhen near Hong Kong by a group of clinicians and scientists from the University of Hong Kong has provided the first concrete evidence for human-to-human transmission of SARS-CoV-2 [ 1 ]. This is an excellent example of how a high-quality clinical study can make a major difference in policy setting. Several important clinical features of COVID-19 have also been documented in this study. First, an attack rate of 83% within the family context is alarmingly high, indicating the high transmissibility of SARS-CoV-2. Second, the clinical manifestations of COVID-19 in this family range from mild to moderate, with more systematic symptoms and more severe radiological abnormalities seen in older patients. Generally, COVID-19 appears to be less severe than SARS. Third, an asymptomatic child was found to have ground-glass opacities in his lung and SARS-CoV-2 RNA in his sputum sample. This finding of asymptomatic virus shedding raises the possibility for transmission of SARS-CoV-2 from asymptomatic carriers to others, which is later confirmed by others [ 2 ]. Finally, the presentation of diarrhea in two young adults from the same family also suggests the possibility for gastrointestinal involvement in SARS-CoV-2 infection and fecal–oral transmission. The study has set the stage for the control and management of COVID-19 [ 1 ]. The work was completed timely and the investigators showed great courage and leadership in a very difficult time when the Chinese authority failed to recognize widespread person-to-person transmission of SARS-CoV-2 before January 20, 2020.

Several interesting papers on SARS-CoV-2 and COVID-19 have been published in the past few weeks to report on the evolutionary reservoir [ 3 ], possible intermediate host [ 4 ] and genomic sequence [ 5 ] of SARS-CoV-2 as well as clinical characteristics of COVID-19 [ 6 , 7 ]. In view of these findings and the urgent needs in the prevention and control of SARS-CoV-2 and COVID-19, in this commentary we highlight the most important research questions in the field from our personal perspectives.

The first question concerns how SARS-CoV-2 is transmitted currently in the epicenter of Wuhan. In order to minimize the spreading of SARS-CoV-2, China has locked down Wuhan and nearby cities since January 23, 2020. The unprecedented control measures including suspension of all urban transportation have apparently been successful in preventing further spreading of SARS-CoV-2 to other cities. However, the number of confirmed cases in Wuhan continued to rise. It is therefore crucial to determine whether the rise is due to a large number of infected individuals before the lock down and/or failure in the prevention of widespread intra-familial, nosocomial or community transmission. Based on the number of exported cases from Wuhan to cities outside of mainland China, it was predicted that there might be more than 70,000 individuals infected with SARS-CoV-2 on January 25, 2020 in Wuhan [ 8 ]. This should be determined experimentally in Wuhan as discussed below and it will reveal whether the real numbers of infected people and asymptomatic carriers are indeed underestimated severely. In addition to viral RNA detection, measurement of IgM and IgG antibodies as well as antigens would be very helpful. Several representative residential areas should be selected for detailed analysis so that a big picture can be deduced. The analysis should include all healthy and diseased individuals within the area with the aim of identifying people who have recovered from an infection or are having an active infection. The ratio of asymptomatic carriers should also be determined. The analysis should also be extended to detect RNA and antigen of influenza viruses. The activity of seasonal flu in Wuhan also reached a peak at the beginning of 2020. It will be of interest to see whether the flu season had ended and how many people having a fever now are actually infected with influenza virus. Precision control measures for SARS-CoV-2 should be tailor-designed for high-risk groups based on the results of this analysis. Differentiating people having a flu and preventing them from infecting with SARS-CoV-2 in a hospital setting might also be critical.

The second question is how transmissible and pathogenic is SARS-CoV-2 in tertiary and quaternary spreading within humans. Continued transmission of SARS-CoV-2 in Wuhan suggests that tertiary and quaternary spreading has occurred. Compared to the primary and secondary spreading during which SARS-CoV-2 was transmitted from animal to human and from human to human, has the transmission rate increased and has the pathogenicity decreased? Alternatively, is the virus less transmissible after several passages in humans? Retrospective analysis of all confirmed cases in Wuhan should be very informative. The answers to the above questions hold the key to the outcome of the outbreak. If the transmission is weakened, the outbreak may ultimately come to an end at which SARS-CoV-2 is eradicated from humans. On the contrary, if effective transmission can be sustained, the chance is increased that SARS-CoV-2 will become another community-acquired human coronavirus just like the other four human coronaviruses (229E, OC43, HKU1 and NL63) causing common cold only. The basic reproductive number (R 0 ) of SARS-CoV-2 has been estimated to be 2.68, resulting in an epidemic doubling time of about 6.4 days [ 8 ]. Other estimates of R 0 could go up to 4, higher than that of SARS-CoV, which is lower than 2. Determining the real R 0 will shed light on whether and to what extent infection control measures are effective.

The third question relates to the importance of asymptomatic and presymptomatic virus shedding in SARS-CoV-2 transmission. Asymptomatic and presymptomatic virus shedding posts a big challenge to infection control [ 1 , 2 ]. In addition, patients with mild and unspecific symptoms are also difficult to identify and quarantine. Notably, the absence of fever in SARS-CoV-2 infection (12.1%) is more frequent than in SARS-CoV (1%) and Middle East respiratory syndrome coronavirus (MERS-CoV; 2%) infection [ 6 ]. In light of this, the effectiveness of using fever detection as the surveillance method should be reviewed. However, based on previous studies of influenza viruses and community-acquired human coronaviruses, the viral loads in asymptomatic carriers are relatively low [ 9 ]. If this is also the case for SARS-CoV-2, the risk should remain low. Studies on the natural history of SARS-CoV-2 infection in humans are urgently needed. Identifying a cohort of asymptomatic carriers in Wuhan and following their viral loads, clinical presentations and antibody titers over a time course will provide clues as to how many of the subjects have symptoms in a later phase, whether virus shedding from the subjects is indeed less robust, and how often they might transmit SARS-CoV-2 to others.

The fourth question relates to the importance of fecal–oral route in SARS-CoV-2 transmission. In addition to transmission via droplets and close contact, fecal–oral transmission of SARS-CoV has been shown to be important in certain circumstances. Gastrointestinal involvement of SARS-CoV-2 infection and isolation of SARS-CoV-2 from fecal samples of patients are in support of the importance of fecal–oral route in SARS-CoV-2 transmission. Although diarrhea was rarely seen in studies with large cohorts [ 6 , 7 ], the possibility of SARS-CoV-2 transmission via sewage, waste, contaminated water, air condition system and aerosols cannot be underestimated, particularly in cases such as the Diamond Princess cruise ship with 3,700 people, among whom at least 742 have been confirmed to be infected with SARS-CoV-2 plausibly as the result of a superspreading event. Further investigations are required to determine the role of fecal–oral transmission in these cases and within the representative residential areas selected for detailed epidemiological studies in Wuhan as discussed earlier.

The fifth question concerns how COVID-19 should be diagnosed and what diagnostic reagents should be made available. RT-PCR-based SARS-CoV-2 RNA detection in respiratory samples provides the only specific diagnostic test at the initial phase of the outbreak. It has played a very critical role in early detection of patients infected with SARS-CoV-2 outside of Wuhan, implicating that widespread infection of the virus had occurred in Wuhan at least as early as the beginning of 2020. This has also pushed the Chinese authority to acknowledge the severity of the situation. Due to difficulties in sampling and other technical issues in this test, at one point in early February clinically diagnosed patients with typical ground glass lung opacities in chest CT were also counted as confirmed cases in order to have the patients identified and quarantined as early as possible. ELISA kits for detection of IgM and IgG antibodies against N and other SARS-CoV-2 proteins have also been available more recently. This has made specific diagnosis of ongoing and past infection possible. Particularly, seroconversion for IgM antibodies normally occurs a few days earlier than that of IgG. ELISA reagents for detection of SARS-CoV-2 antigens such as S and N are still in urgent need, and would provide another test highly complementary to viral RNA detection.

The sixth question concerns how COVID-19 should be treated and what treatment options should be made available. COVID-19 is a self-limiting disease in more than 80% of patients. Severe pneumonia occurred in about 15% of cases as revealed in studies with large cohorts of patients. The gross case fatality is 3.4% worldwide as of February 25, 2020. This rate is 4.4% for patients in Wuhan, 4.0% for patients in Hubei and 0.92% for patients outside of Hubei. The exceedingly high fatality in Wuhan might be explained by the collapse of hospitals, a large number of undiagnosed patients, suboptimal treatment or a combination of these. Up to date, we still do not have any specific anti-SARS-CoV-2 agents but an anti-Ebola drug, remdesivir, may hold the promise. As a nucleotide analog, remdesivir was shown to be effective in preventing MERS-CoV replication in monkeys. Severity of disease, viral replication, and lung damage were reduced when the drug was administered either before or after infection with MERS-CoV [ 10 ]. These results provide the basis for a rapid test of the beneficial effects of remdesivir in COVID-19. Other antiviral agents worthy of further clinical investigations include ribavirin, protease inhibitors lopinavir and ritonavir, interferon α2b, interferon β, chloroquine phosphate, and Arbidol. However, we should also bear in mind the side effects of these antiviral agents. For example, type I interferons including interferon α2b and interferon β are well known for their antiviral activity. Their beneficial effects at an early phase of infection are well expected. However, administration at a later stage carries the risk that they might worsen the cytokine storm and exacerbate inflammation. Notably, steroids have been experimentally used widely in the treatment of SARS and are still preferred by some Chinese physicians in the treatment of COVID-19. It is said to be capable of stopping the cytokine storm and preventing lung fibrosis. However, the window in which steroids might be beneficial to patients with COVID-19 is very narrow. In other words, steroids can only be used when SARS-CoV-2 has already been eliminated by human immune response. Otherwise, SARS-CoV-2 replication will be boosted leading to exacerbation of symptoms, substantial virus shedding, as well as increased risk for nosocomial transmission and secondary infection. In this regard, it will be of interest to determine whether the report of fungal infection in the lungs of some patients in Wuhan might be linked to misuse of steroids. Nevertheless, the screening of new pharmaceuticals, small-molecule compounds and other agents that have potent anti-SARS-CoV-2 effects will successfully derive new and better lead compounds and agents that might prove useful in the treatment of COVID-19.

The seventh question is whether inactivated vaccines are a viable option for SARS-CoV-2. The chance that SARS-CoV-2 will become endemic in some areas or even pandemic has increased in view of its high transmissibility, asymptomatic and presymptomatic virus shedding, high number of patients with mild symptoms, as well as the evidence for superspreading events. Thus, vaccine development becomes necessary for prevention and ultimate eradication of SARS-CoV-2. Inactivated vaccines are one major type of conventional vaccines that could be easily produced and quickly developed. In this approach, SARS-CoV-2 virions can be chemically and/or physically inactivated to elicit neutralizing antibodies. In the case of SARS-CoV and MERS-CoV, neutralizing antibodies were successfully and robustly induced by an inactivated vaccine in all types of animal experiments, but there are concerns about antibody-dependent enhancement of viral infection and other safety issues. While inactivated vaccines should still be tested, alternative approaches include live attenuated vaccines, subunit vaccines and vectored vaccines. All of these merit further investigations and tests in animals.

The eighth question relates to the origins of SARS-CoV-2 and COVID-19. To make a long story short, two parental viruses of SARS-CoV-2 have now been identified. The first one is bat coronavirus RaTG13 found in Rhinolophus affinis from Yunnan Province and it shares 96.2% overall genome sequence identity with SARS-CoV-2 [ 3 ]. However, RaTG13 might not be the immediate ancestor of SARS-CoV-2 because it is not predicted to use the same ACE2 receptor used by SARS-CoV-2 due to sequence divergence in the receptor-binding domain sharing 89% identity in amino acid sequence with that of SARS-CoV-2. The second one is a group of betacoronaviruses found in the endangered species of small mammals known as pangolins [ 4 ], which are often consumed as a source of meat in southern China. They share about 90% overall nucleotide sequence identity with SARS-CoV-2 but carries a receptor-binding domain predicted to interact with ACE2 and sharing 97.4% identity in amino acid sequence with that of SARS-CoV-2. They are closely related to both SARS-CoV-2 and RaTG13, but apparently they are unlikely the immediate ancestor of SARS-CoV-2 in view of the sequence divergence over the whole genome. Many hypotheses involving recombination, convergence and adaptation have been put forward to suggest a probable evolutionary pathway for SARS-CoV-2, but none is supported by direct evidence. The jury is still out as to what animals might serve as reservoir and intermediate hosts of SARS-CoV-2. Although Huanan seafood wholesale market was suggested as the original source of SARS-CoV-2 and COVID-19, there is evidence for the involvement of other wild animal markets in Wuhan. In addition, the possibility for a human superspreader in the Huanan market has not been excluded. Further investigations are required to shed light on the origins of SARS-CoV-2 and COVID-19.

The ninth question concerns why SARS-CoV-2 is less pathogenic. If the reduced pathogenicity of SARS-CoV-2 is the result of adaptation to humans, it will be of great importance to identify the molecular basis of this adaptation. The induction of a cytokine storm is the root cause of pathogenic inflammation both in SARS and COVID-19. SARS-CoV is known to be exceedingly potent in the suppression of antiviral immunity and the activation of proinflammatory response. It is therefore intriguing to see how SARS-CoV-2 might be different from SARS-CoV in interferon-antagonizing and inflammasome-activating properties. It is noteworthy that some interferon antagonists and inflammasome activators encoded by SARS-CoV are not conserved in SARS-CoV-2. Particularly, ORF3 and ORF8 in SARS-CoV-2 are highly divergent from ORF3a and ORF8b in SARS-CoV that are known to induce NLRP3 inflammasome activation. ORF3 of SARS-CoV-2 is also significantly different from the interferon antagonist ORF3b of SARS-CoV. Thus, these viral proteins of SARS-CoV and SARS-CoV-2 should be compared for their abilities to modulate antiviral and proinflammatory responses. The hypothesis that SARS-CoV-2 might be less efficient in the suppression of antiviral response and the activation of NLRP3 inflammasome should be tested experimentally.

Much progress has been made in the surveillance and control of infectious diseases in China after the outbreak of SARS-CoV in 2003. Meanwhile, virological research in the country has also been strengthened. The new disease report and surveillance system did function relatively well during the 2009 pandemic of swine flu. New viral pathogens such as avian influenza virus H7N9 and severe-fever-with-thrombocytopenia syndrome bunyavirus have also been discovered in recent years [ 11 , 12 ], indicating the strength and vigor of Chinese infectious disease surveillance and virological research. However, the ongoing outbreak of SARS-CoV-2 has not only caused significant morbidity and mortality in China, but also revealed major systematic problems in control and prevention of infectious diseases there. Unfortunately, many of the lessons from the 2003 outbreak have not been learned. Importantly, disease control professionals, practicing physicians and scientists are disconnected in the fight against SARS-CoV-2 and COVID-19. In addition, important decisions were not made by experts in the field. Hopefully, these issues will be dealt with swiftly and decisively during and after the outbreak.

Above we have discussed the two possibilities that this outbreak will unfold. If SARS-CoV-2 is not eliminated from humans through quarantine and other measures, it can still be eradicated by vaccination. If it attenuates to become another community-acquired human coronavirus causing mild respiratory tract disease resembling the other four human coronaviruses associated with common cold, it will not be a disaster either. Before SARS-CoV-2 attenuates further to a much less virulent form, early diagnosis and improved treatment of severe cases hold the key to reduce mortality. We should remain vigilant, but there are grounds for guarded optimism. Redoubling our research efforts on SARS-CoV-2 and COVID-19 will solidify the scientific basis on which important decisions are made.

Acknowledgements

We thank Pearl Chan, Hinson Cheung, Terence Lee and Kam-Leung Siu for critical reading of the manuscript.

Authors’ contributions

KSY and DYJ wrote the manuscript with inputs from ZWY, SYF and CPC. All authors read and approved the final manuscript.

Coronavirus research in our laboratory was funded by the Hong Kong Health and Medical Research Fund (HKM-15-M01) and Hong Kong Research Grants Council (T11-707/15-R).

Availability of data and materials

Ethics approval and consent to participate, consent for publication, competing interests.

No potential conflict of interest was reported by the authors.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Questions About COVID-19 and Your Research

June 28, 2021

As the COVID-19 pandemic continues to evolve, various Harvard restrictions and processes that were in place have now been re-visited. Moving forward, take the following into consideration when conducting research with human subjects:

• All research and on-campus activity, should still follow Harvard and local school/department guidelines. For instance, this means that personnel who have not yet been authorized to work on campus will need to check with their departments (or divisions or schools) about the appropriate process to obtain authorization prior to the August 2 nd general return date.
• the most up to date University guidance
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• SEAS & FAS Division of Science: Coronavirus FAQs
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• Note that Harvard continues to require masks indoors, regardless of vaccination status. This guidance will be updated as Harvard requirements and local community incidence changes. Please also check local school or division for more local guidance.
• Some previous restrictions placed on human subjects research have been lifted. Currently physical distancing is no longer required for those vaccinated in all research locations. Please check with your school/division/department for any local guidelines.
• Irrespective of location, individuals interacting with human subjects are advised to continue to wear surgical masks as vaccination status of study participants cannot be assumed. Research study personnel should let participants decide if they would like to wear a mask if the study procedures allow it.
• Researchers may wish to inform their study population of the current COVID-19 status on campus , or in the study location if elsewhere , including level of community transmission of COVID-19 and COVID-19 vaccination coverage.  It continues to be recommended that those that are unvaccinated and at high-risk for COVID-19 complications or immunocompromised not take part in research.
• It is recommended that researchers conduct a brief screening with study participants prior to the study visit. Sample questions may be found below.
• Other restrictions such as those involving travel and working in other locations or at other institutions are still in place. It is important for researchers to follow any guidelines or instructions from the specific facility or location where in-person research would occur. As some research may occur in another state, with another institution, or under the direction of another IRB (as in a reliance agreement situation), this is especially important.  It is the responsibility of the Study Team to keep apprised of potential restrictions and conduct their study accordingly.
• Researchers planning to hire professional companies (survey organization and the like) in other states or countries should do due diligence to make sure that these organizations are taking reasonable coronavirus precautions and are fully aware of local conditions and government restrictions. In particular, Harvard should not be asking these organizations to be engaging in practices that are riskier than their normal business operations.

As restrictions relax, there are still ongoing public health best practices and guidelines to pay attention to:

• Practice safe distancing, when necessary and appropriate.
• Wash or sanitize your hands often and continue respiratory etiquette.
• Perform disinfection of frequently touched objects and surfaces.

Harvard has upgraded its ventilation systems, including installing HEPA filtration units as needed, and will continue to routinely assess airflow. Should you have any questions, please check with your department administrator or building manager. For research off-campus, please be aware that a ventilated space (particularly with open windows) is safer than an unventilated one.

You may access the archive of COVID-19 research information, research restrictions and processes here - https://cuhs.harvard.edu/questions-about-covid-19-and-your-research-ARCHIVE

Sample questions for COVID-19 screening https://projects.iq.harvard.edu/files/scictr/files/crimson_clear_paperform_as_of_06072020.pdf

Q1: ARE YOU EXPERIENCING ANY OF THE FOLLOWING SYMPTOMS? (CHECK ALL THAT APPLY)

☐ Fever, chills, or feeling feverish

☐ New cough (not related to chronic condition)

☐ Shortness of breath or difficulty breathing

☐ New fatigue

☐ Muscle or body aches

☐ New headache

☐ New loss of taste or smell

☐ Sore throat

☐ New nasal congestion or new runny nose (not related to seasonal allergies)

☐ Nausea or vomiting

☐ Diarrhea  

If ANY of the above apply, inform the study participant that they will not be permitted to come to the study visit on that day and that they should contact their health care provider. For medical emergencies, call 911.

If NONE of the above apply, proceed to Q2

Q2: IN THE LAST 14 DAYS, HAVE YOU BEEN IN CLOSE CONTACT WITH ANYONE WHO HAS TESTED POSITIVE FOR COVID-19? (CHECK BOX)

If Yes, the study participant believes that they were exposed to a confirmed case of COVID-19, inform them that they will not be permitted to attend the study visit on that day and that they should contact their health care provider. For medical emergencies, call 911.

If No, inform study participant that they may come to the study visit. Remind them to always wear a facemask as well as any location or study specific information that they should know about.