MUIThe coronavirus disease 2019 (COVID-19) pandemic, like other public health emergencies, has exposed gaps in our preparedness and mitigation measures. Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pandemic also has been associated with inequalities in health care access and outcomes,1–4 increased violence against women and girls,5,6 heightened anxiety and depression,7–12 and concerning reports of bias and discrimination.13–18 Women in science, technology, engineering, mathematics, and medicine (STEMM) fields and NIH grantees are also facing difficulties related to their careers, their research, their families, and their mental and physical health.

COVID-19 presents an unprecedented opportunity to invest in rigorous, responsive, and responsible health research to understand more clearly how to prevent and treat disease for everyone. This pandemic underscores the imperative of systematically considering biological sex and social determinants of health to strengthen our collective capacity to respond equitably to COVID-19—as well as to any future outbreak or pandemic-related threats. Considering sex, as well as gender and other social determinants of health, promotes the development and deployment of effective diagnostics, treatments, and interventions that are relevant to the entire population. Further, continued support of the biomedical workforce—clinicians and researchers—will help mitigate the effects of the pandemic.

This webpage describes: (1) NIH efforts to ensure that research on COVID-19 appropriately incorporates consideration of sex and gender influences; (2) the pandemic’s effects on the careers of women in STEMM fields and biomedical researchers and how NIH is supporting them; and (3) the recently published NIH-Wide Strategic Plan for COVID-19 Research and how it intersects with ORWH’s mission areas. 

Socially constructed gender roles and norms exist alongside biological differences. Like biology, gender plays a significant role in health outcomes. Therefore, in studies of COVID-19, as in many areas of research, gender emerges as an important consideration. Applying a multidimensional framework to the study of COVID-19 (see Figure 4 of the Trans-NIH Strategic Plan for Women’s Health Research) ensures that researchers consider the range of biological and social factors—and their intersections—that influence women’s health across the life course. ORWH has developed a one-page guiding principles document related to COVID-19 and a COVID-19-based annotated bibliography. These resources provide a rationale for applying a sex-and-gender lens to the pandemic, areas of research where COVID-19 and the health of women intersect, and potential COVID-19-related research topics in line with ORWH’s mission.

Sex and gender, whether considered independently or at their intersection, are essential determinants of health and influence disease prevalence, progression, and outcomes. The need to consider sex for research to be reproducible and relevant for all people warranted a separate NIH policy: Consideration of Sex as a Biological Variable (SABV) in NIH-funded Research. Though the proportion of confirmed COVID-19 cases between the sexes is roughly equal, the proportion of deaths is higher in males. It is ORWH’s responsibility to ensure NIH-funded research takes a deep dive into several possible explanations—some rooted in sex as a biological variable and others in socially constructed gender roles and norms—regarding this male bias in COVID-19 vulnerability.

ORWH, the NIH Coordinating Committee on Research on Women’s Health (CCRWH), and other NIH organizations are working in concert to ensure that NIH-supported COVID-19 research will incorporate, as appropriate, a thorough consideration of sex and gender in compliance with Federal mandates to yield robust, generalizable scientific findings. NIH’s inclusion policies (Inclusion Across the Lifespan and Inclusion of Women and Minorities as Subjects in Clinical Research) and SABV policy informed the creation of the Trans-NIH Strategic Plan for Women’s Health Research to guide NIH efforts and ensure that NIH-funded research will benefit all populations. Incorporating a sex-and-gender lens into NIH’s response to COVID-19 offers several unique opportunities to promote rigorous research and advance health equity, including strengthening vaccine efficacy and dosing for all sexes; enhancing investigations of new therapeutics; exploring sex differences in medication risk profiles; elucidating gender-related factors affecting treatment adherence, access to health care, and health-seeking behaviors; and understanding the long-term mental and physical health consequences of isolation, stress, economic hardship, and other pandemic-associated factors.

Below, we describe a few areas of scientific inquiry related to COVID-19 in which sex and gender considerations have deepened our understanding of the disease and associated public health issues.

Mental Health. The pandemic has widened the stress-level gap between men and women, with women being more likely to report worry or stress related to the coronavirus. A preliminary study by Abi Adams-Prassl, D.Phil., and colleagues19 assessed the mental health effects of the pandemic and associated stay-at-home orders in the United States. The researchers analyzed two waves of geographically representative survey data (from March and April 2020; 4,000 participants per wave). Dr. Adams-Prassl and colleagues found a decline in mental health, and data disaggregated by sex showed that the large negative effect was driven almost entirely by women. (There was a 66% increase in the pre-pandemic mental health gap between men and women.) Additionally, the researchers found that the increases in financial worries and child care responsibilities did not solely explain the negative effect on women’s mental health.

Intimate Partner Violence and Gender-Based Violence. Data indicate an increased risk of intimate partner violence (IPV) while stay-at-home directives are in effect.20 Access to health care services, including IPV support services, is limited while movement is restricted, which increases the urgency of identifying, reporting, and responding to IPV. As part of a holistic response to violence against women, the entire health care system—including community-based COVID-19 diagnostic settings—can act in a coordinated way to intervene on behalf of victims of violence by incorporating IPV screening into all clinical diagnostics.

Pregnancy, Breastfeeding, and Reproductive Health. Pregnancy is associated with alterations in the immune system, and pregnant women are more susceptible to respiratory pathogens and to the development of severe pneumonia than the general population. These vulnerabilities might make pregnant women more susceptible to COVID-19 infection than the general population, especially if they have chronic diseases or maternal complications.21,22,23 Limited data from previous respiratory viral pandemics—e.g., those caused by influenza, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS)—suggest that COVID-19 infection could result in more severe illness in pregnant women and an increased risk of pregnancy and neonatal complications.24

Although preliminary information about COVID-19 in pregnant women suggests that they are not more severely affected than the general population, pregnant women have experienced higher rates of COVID-19-related hospitalizations and ICU admissions.25 COVID-19 data reported on pregnant women have been limited, and more studies comparing pregnant women with nonpregnant women of similar ages (rather than with all COVID-19 patients) are needed.

Sexual and Gender Minorities. Prior to the COVID-19 pandemic, sexual and gender minorities (SGMs) experienced unique health disparities, including a poor health-related quality of life;26 greater risk of suicide;27,28 increased risk of mistreatment, discrimination, and violence;29 post-traumatic stress disorder;30 and other stresses and stigmas that have been associated with negative clinical effects.31 Further health and health-related disparities exist for SGMs from minority racial and ethnic groups, and some SGM subpopulations have an increased risk of diabetes,32 HIV,33,34 fatal violence,35 unemployment,36 and/or additional stress and stigma.37

No direct evidence indicates specific vulnerabilities of SGMs to COVID-19, in large part because data on sexual orientation and gender identity (SOGI) are collected infrequently and inconsistently. However, in many cases, the pandemic may function to exacerbate the health disparities of SGMs described above. SGMs face particular challenges during the COVID-19 pandemic, including greater risk of financial hardship than the general population, increased risk of health complications caused by chronic conditions (e.g., asthma, cardiovascular disease, obesity, cancer, HIV/AIDS), and higher rates of smoking, vaping, and other substance use.38 Within SGM populations, racial and ethnic minorities are likely to be at even greater risk for adverse pandemic-related outcomes because of their additional financial and health challenges.39 NIH, with guidance from its Sexual and Gender Minority Research Office (SGMRO), is helping to ensure that SGM populations are included in COVID-19-related research initiatives and that investigators are collecting and analyzing data on sexual orientation and gender identity in their COVID-19- and pandemic-related studies.

The effects of COVID-19 on the biomedical clinical and research workforces are staggering. The majority of health care providers are women, and many researcher-clinicians have been overwhelmed physically and mentally by struggling to provide direct care to seriously ill patients while still attending to their research. Many women scientists are challenged further by their domestic roles as principal caregivers. With many schools and day care centers closed and education systems adopting at-home virtual learning models, a disproportionate number of women have increased responsibilities for child care, home-schooling, and managing their children’s psychological responses to COVID-19—all while navigating their own pandemic-related stress, hardships, and health issues. Since these increased child care responsibilities began, the percentage of female STEMM authorship has dropped from 35.9% in December 2019 to 20.2% in April 2020.40 Women in STEMM have consistently authored 20% of working papers since 2015 but have contributed only 12% of the publications related to COVID-19 research.41

However, COVID-19 has created opportunities to marshal resources; center diverse voices, including those of women and of racial and ethnic minorities; and coordinate research in a manner responsive to social determinants of health and health equity. ORWH has seized these opportunities to address career issues for women in STEMM and to highlight the voices of women scientists across the world. NIH, along with many other research institutions and universities, has taken action to mitigate the career effects of the pandemic on researchers by providing timely information, offering supplemental grant opportunities for researchers affected by COVID-19, and affording other flexibilities (e.g., establishing expedited grant-application submission processes, accelerating peer review and updating the guidance for NIH peer reviewers, and extending submission deadlines for grantees).

Early-Stage Researchers. Women beginning STEMM careers face particular challenges during the pandemic. Research demonstrates the critical importance of STEMM mentorship, particularly of guidance from senior-level women to junior women scientists from underrepresented minority populations. Unfortunately, with the pandemic, many mentors have necessarily dedicated themselves to clinical duties and have been unable to provide much-needed support to junior investigators. While some institutions provide trainee stipends, others are furloughing fellows. Hiring and advancement have slowed, with junior investigators facing hiring freezes and additional challenges during periods of career transition (e.g., from mentored research awardees with K99 grants to independent tenure-track faculty members or equivalent positions).

ORWH’s Careers section co-leads and provides oversight on several programs and supplemental funding opportunities to support early-stage investigators (ESIs) experiencing critical life events (e.g., Administrative Supplement to Promote Research Continuity and Retention of NIH Mentored Career Development [K] Award Recipients and Scholars [NOT-OD-20-054] and Administrative Supplement for Continuity of Biomedical and Behavioral Research Among First-Time Recipients of NIH Research Project Grant Awards [NOT-OD-20-055]). Through these mechanisms, several co-funding applications to support researchers providing care for family members with COVID-19 were awarded.

In addition, ORWH provided additional support to researchers participating in the Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) program, ORWH’s signature K12 program. NIH afforded BIRCWH Scholars new flexibilities and advised them accordingly. Some qualifying BIRCWH Scholars received extended support, such as permission to remain in the program in spite of pandemic-related program limitations, extended salary and research support in response to university lockdowns, and grant funding opportunities facilitated with other NIH Institutes, Centers, and Offices (ICOs) to assist at-risk researchers during the pandemic.

Information and Support from the NIH Office of Extramural Research (OER). OER has developed and regularly updates the COVID-19: Information for NIH Applicants and Recipients of NIH Funding webpage. This webpage should be the first stop for NIH grant applicants and NIH-supported investigators, fellows, and trainees looking for additional guidance and up-to-date information on the effect of the public health emergency on NIH-supported research. The OER webpage includes information to help investigators continue their research, including instructions for submitting proposals, guidance for animal welfare, instructions for human subjects and clinical trials, and descriptions of flexibilities available to applicants and recipients of Federal financial assistance affected by COVID-19. It also includes an FAQ pertaining to delays in research progress and how to request grant extensions (e.g., ESI extensions, National Research Service Award payback extensions, K99 to R00 transition extensions, fellowship extensions, and K99 eligibility extensions). A blog post by Michael Lauer, M.D., NIH’s Deputy Director for Extramural Research, titled “Accepting Preliminary Data as Post-Submission Material and Other COVID-19-Related Application Flexibilities,” provides more information on pandemic-era flexibilities and concessions to NIH-supported researchers.

NIH Offers Funding Opportunities on COVID-19. NIH now offers emergency competitive revision and urgent competitive revision funding to qualifying current grantees intending to shift focus to the novel coronavirus. This approach enables NIH to leverage resident expertise and quickly provide additional funds to researchers through an expedited review process. More information is available here. ORWH has co-sponsored several funding opportunities for research on the social, economic, behavioral, and health consequences of COVID-19, particularly as they pertain to the health of women, health disparity populations, and other vulnerable groups.

Research on the Pandemic’s Effects on STEMM Careers. Partnering with the Scientific Workforce Diversity (SWD) Office and other ICOs, ORWH has enthusiastically participated in developing a survey tool examining the effects of the COVID-19 pandemic on the biomedical research workforce and focusing on the differential effects on vulnerable groups, such as women of color and women with intersecting identities. NIH will continue to solicit input from its research community and devise new strategies or repurpose existing ones to mitigate the devastating effects of the pandemic on the biomedical workforce.

The National Academies of Sciences, Engineering, and Medicine (NASEM)  recently published The Impact of COVID-19 on the Careers of Women in Academic Sciences, Engineering, and Medicine , a book-length report detailing the pandemic’s disruption of the professional development of women in STEMM fields. The publication describes how lockdowns and mitigation efforts disrupted global scientific conferences, laboratory research, work routines, and virtually every aspect of professional activity. Initial research and evidence cited in the report indicate that COVID-19 had particularly adverse effects on the engagement, experience, and retention of women in STEMM, and may have resulted in the loss of some pre-pandemic achievement gains made by women in academic science. The NASEM report also speculates about how these disruptions might influence the careers of women in STEMM, both positively and negatively, in future years.

NIH recently released the NIH-Wide Strategic Plan for COVID-19 Research. The strategic plan describes five priorities for accelerating the development of therapeutic interventions, vaccines, and diagnostics:

  • Improve Fundamental Knowledge of SARS-CoV-2 and COVID-19. NIH-supported researchers will continue to work together with their partners to understand the biology of SARS-CoV-2 infection and COVID-19 outcomes, as well as the impact that infection and disease have on individuals, communities, and public health. This fundamental knowledge will be used to identify novel approaches for developing effective diagnostics, prevention strategies, and treatments.
  • Advance Detection and Diagnosis of COVID-19. As Americans return to public spaces, a vital component of the Nation’s strategy is detecting, diagnosing, and surveilling the population to identify and quarantine COVID-19 cases and track the spread of the virus. Despite an exponential increase, current testing capacity still is insufficient to meet the Nation’s needs—both in terms of the number of tests available and their ability to deliver answers rapidly at the point of care. To develop more accurate, rapid, scalable, and accessible tests, NIH is committed to accelerating the development, validation, and commercialization of innovative COVID-19 testing technologies, focusing efforts both on viral tests—which indicate whether a person has a current infection—and on antibody, or serological, tests, which indicate whether a person has had a previous infection. To this end, NIH will continue to advance a wide range of initiatives to improve or repurpose current technologies and advance new ones.
  • Advance the Treatment of COVID-19. When the COVID-19 pandemic began, Food and Drug Administration–approved treatments for coronaviruses did not exist. Normally, the discovery and development of a new therapeutic is a years-long process. The unprecedented need brought on by the COVID-19 pandemic has compelled a paradigm shift in that process to enhance the sharing of knowledge, resources, and infrastructure among academics, Federal agencies, and industry. Through such a shift, the goal is to compress the timeline for discovery and development of therapeutics to treat COVID-19 from years to months while continuing to apply rigorous standards to ensure safety and efficacy. To this end, NIH assembled the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership and will continue to work closely with other Government agencies organized through Operation Warp Speed.
  • Improve Prevention of SARS-CoV-2 Infection. Critical to resolving the current COVID-19 pandemic and preventing future outbreaks is the development of countermeasures to stop transmission of the virus and prevent new infections. By supporting the development of new vaccines, behavioral and community interventions, and effective strategies for implementation of these countermeasures, NIH will create preventive interventions that have the potential to reduce the incidence of new SARS-CoV-2 infections across the country. The NIH approach will leverage existing knowledge, tools, networks, and infrastructure—in addition to developing and implementing novel approaches—to prevent new SARS-CoV-2 infections.
  • Prevent and Redress Poor COVID-19 Outcomes in Health Disparity and Vulnerable Populations. The impact of COVID-19 on health disparity,42 underserved, and vulnerable populations in the United States and abroad must be urgently addressed. Preliminary data show consistent differences in COVID-19 prevalence and mortality across different age, racial, and ethnic groups and among other specific populations (e.g., people with asthma or diabetes).43 The underlying causes are complex and include social and structural determinants of health—such as social, economic, and political mechanisms that generate inequalities in society (e.g., discrimination and economic and educational disadvantages)—and differences in health care access and quality. These concerns are amplified in lower- and middle-income countries with fragile health care systems; densely populated urban areas, where physical distancing is often not possible; and communities with high rates of chronic health conditions. A deeper understanding of the underlying causes that may exacerbate the spread and morbidity or mortality of COVID-19 in the United States—as well as different countries around the globe—may allow the scientific, public health, and clinical communities to implement interventions to mitigate negative outcomes through better prevention, testing, and treatment of COVID-19. NIH aims to address key questions related to the differential impacts of the COVID-19 pandemic. These include understanding barriers to adherence to different mitigation strategies among populations and differences in risk and resilience based on biological factors, gender, race and ethnicity, socioeconomic status, ability, and other social and structural determinants of health. Ultimately, the United States will not be able to control the pandemic alone. NIH will continue to collaborate with the global scientific community not only to understand the spread of COVID-19 but also to develop and distribute the diagnostics, treatments, and vaccines needed to control COVID-19 on a global scale.

Many of the goals of the NIH-Wide Strategic Plan for COVID-19 Research intersect with ORWH mission areas. ORWH will continue to advance fulfillment of these goals through co-funding initiatives and other efforts. These ORWH mission areas include:

  • NIH Policies on Inclusion and Sex as a Biological Variable (SABV). NIH’s inclusion policies (Inclusion Across the Lifespan and Inclusion of Women and Minorities as Subjects in Clinical Research) and SABV policy informed the creation of the NIH-Wide Strategic Plan for COVID-19 Research and will ensure that NIH’s efforts and NIH-funded research will benefit all populations. Studies to examine biological factors that influence individual susceptibility to infection—such as age, sex, gender, genetics, and environment—are already in progress. Researchers also are examining social factors related to COVID-19, such as health disparities based on race and ethnicity, including their influence on biological factors. Also planned are studies of risk factors, complications, and long- and short-term outcomes in older adults, children, and adolescents. In addition, NIH has established a multipronged approach to discover or repurpose promising candidate therapies by using human cell–based and animal models to identify those therapies that might interfere with the production of the virus or the ability of the virus to infect cells; this research will incorporate the SABV policy. 
  • Understudied, Underrepresented, and Underreported (U3) Interdisciplinary Research. NIH recognizes the disproportionate impact of COVID-19 on health disparity, vulnerable, and U3 populations and is striving to mitigate it by identifying the underlying factors and barriers that contribute to the staggering losses in these communities. Inclusion of these populations in clinical trials for diagnostics and interventions will be a critical part of NIH’s pandemic response, as will exploring communication strategies and ways to improve access to care and interventions for at-risk populations. The disproportionate impact of COVID-19 on U3 populations necessitates an intentional, inclusive approach to descriptive studies of the disease, the development of diagnostic tests, the evaluation of vaccines, and the testing of new therapies. Including populations such as African Americans, Latinx, American Indians, Alaska Natives, older adults, people experiencing homelessness, and patients with comorbidities—vital to the study of any disease—is essential to the integrity of scientific inquiries into COVID-19 and to addressing a pandemic. In particular, one of the key components of the Rapid Acceleration of Diagnostics (RADx) initiative, RADx Underserved Populations (RADx-UP), will leverage existing community partnerships to build community-engaged demonstration projects. These projects will focus on identifying effective implementation strategies to enable and enhance testing for underserved and vulnerable populations.
  • Maternal Health. Objective 5.2 of the strategic plan articulates how NIH will strive to understand and address COVID-19 maternal health and pregnancy outcomes. Ongoing and future studies will include consideration of COVID-19 and maternal morbidity, pregnancy-related alterations to the immune system, preterm birth, infant health, prenatal and postnatal care, rate of cesarean section delivery, possible mother-to-fetus transmission, possible mother-to-child transmission at birth, and possible transmission via breastfeeding. At least one team of vaccine developers is incorporating breastfeeding women into its SARS-CoV-2 Phase III trial.44 Independent of COVID-19, women in the United States from underserved populations face substantially higher rates of pregnancy-related complications (e.g., severe maternal morbidity) and pregnancy-related death compared with non-Hispanic White women. As such, NIH will leverage existing research on maternal morbidity and mortality to investigate questions related to pregnancy and COVID-19 among different populations. 

You can read the NIH-Wide Strategic Plan for COVID-19 Research and learn more about how the framework aims to mobilize the biomedical research response to the pandemic here.

MUI

Disclaimer: The citations on this page, in the guiding principles document, and in the annotated bibliography constitute neither an endorsement by ORWH or NIH nor an indication that these references have been peer-reviewed or NIH-funded.

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11 Liu, C. H., et al. (2020). Psychiatry Research. PMID: 32512357.
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16 Chen, J. A., et al. (2020). American Journal of Public Health. PMID: 32941063.
17 Bagcchi, S. (2020). The Lancet Infectious Diseases. PMID: 32592670.
18 Cobb, J. S. (2020, May 5). Transgender people face discrimination, violence amid Latin American quarantines. Reuters.
19 Adams-Prassl, A., et al. (2020). Cambridge-INET Working Paper WP2037.
20 Boserup, B., et al. (2020). American Journal of Emergency Medicine. PMID: 32402499. 
21 Naidu, S. A. G., et al. (2020). Journal of Dietary Supplements. PMID: 33164601.
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24 Dana, P. M., et al. (2020). InfezMed. PMID: 32532938.
25 Centers for Disease Control and Prevention. (2020, November 5). Data on COVID-19 during pregnancy: severity of maternal illness. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/special-populations/pregnancy-data-on-covid-19.html
26 Charlton, B. M., et al. (2018). BMJ Open. PMID: 30049672.
27 Haas, A. P., et al. (2011). Journal of Homosexuality. PMID: 21213174.
28 McDermott, E., et al. (2018). Journal of Public Health (Oxf.). PMID: 29045707.
29 James, S. E., et al. (2016). The report of the 2015 U.S. Transgender Survey. National Center for Transgender Equality.
30 Livingston, N. A., et al. (2020). Current Treatment Options in Psychiatry. PMID: 32421099.
31 Meyer, I. H. (2015). Psychology of Sexual Orientation and Gender Diversity 2(3):209–213.
32 Beach, L. B., et al. (2018). LGBT Health. PMID: 29377760.
33 Centers for Disease Control and Prevention. (2020). Diagnoses of HIV infection in the United States and dependent areas, 2018. https://www.cdc.gov/hiv/library/reports/hiv-surveillance/vol-31/index.html
34 Centers for Disease Control and Prevention. (2020). Estimated HIV incidence and prevalence in the United States, 2014–2018. HIV Surveillance Supplemental Report 25(1).
35 Human Rights Campaign. (2017). A time to act: fatal violence against transgender people in America 2017.
36 Badgett, M. V. L., et al. (2019). LGBT poverty in the United States. UCLA School of Law Williams Institute.
37 Balsam, K. F., et al. (2011). Cultural Diversity & Ethnic Minority Psychology. PMID: 21604840.
38 Whittington, C., et al. (2020). The lives & livelihoods of many in the LGBTQ community are at risk amidst COVID-19 crisis. Human Rights Campaign.
39 Human Rights Campaign. (2020). The impact of COVID-19 on LGBTQ communities of color.
40 Vincent-Lamarre, P., et al. (2019, May 19). The decline of women’s research production during the coronavirus pandemic. Nature Index.
41 Viglione, G. (2020). Nature. PMID: 32433639.
42 Health disparity populations include Blacks, Latinx, American Indians, Alaska Natives, Asian Americans, Native Hawaiians and other Pacific Islanders, socioeconomically disadvantaged populations, underserved rural populations, and sexual and gender minorities.
43 Populations with increased risk of COVID-19 include residents of chronic care and assisted living facilities; community-dwelling older adults; individuals with rare diseases; individuals with cognitive impairment or dementia; homeless populations; incarcerated populations and those involved with the criminal justice system; adults with medical comorbidities; pregnant women; children and adolescents; individuals with substance use disorders or severe mental illness; those living in congregate housing; people who have visual, hearing, communication, or mobility impairment; detainees in immigration centers; migrant communities; individuals living on tribal lands or reservations; and communities that are exposed to high rates of air pollution or other toxic exposures. Individuals who are on the front lines of health care during the COVID-19 pandemic and those working in essential business operations also are at higher risk for COVID-19.
44 Johnson & Johnson. (2020). Clinical protocol: a randomized, double-blind, placebo-controlled Phase 3 study to assess the efficacy and safety of Ad26.COV2.S for the prevention of SARS-CoV-2-mediated COVID-19 in adults
aged 18 years and older
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