The International Network for Epidemiology in Policy (INEP) is a consortium of 24 epidemiological
societies based around the globe (https://www.epidemiologyinpolicy.org/). INEP’s mission is to promote
the use of integrity, equity, and evidence in health-related policy making.

Epidemiology is the study of the distribution and determinants of infectious or chronic diseases. The
purpose of this letter is to highlight the role of epidemiologists in the generation of high-quality research to
combat SARS-CoV-2 and COVID-19. Several organizations are calling for such research to answer a
multitude of pressing questions about the pandemic. These organizations include the Cochrane
Collaboration,1 Canadian Institutes of Health Research,2 National Institute for Health and Care Excellence,3
and National Institutes of Health,4 among others.

What do epidemiologists do? Epidemiologists are trained to conduct high-quality research in conformity
with the tenets of evidence-based medicine and practice.5–8 Epidemiologists provide methodological and
translation-to-action research expertise to develop and conduct studies7 that are urgently needed to limit the
spread of SARS-CoV-2 and COVID-19. Examples of these studies include vaccine trials for SARS-CoV-
2, efficacy trials to examine pharmaceutical and non-pharmaceutical interventions for COVID-19,
observational studies to identify and protect vulnerable subgroups of the population (e.g., seniors9, people
of color,8 essential workers,9 institutionalized populations10), and population-level studies to obtain
community data for use in disease models that are designed to predict the future incidence and prevalence
of COVID-19. Epidemiologists can also develop studies to investigate items such as infection prevention;
acute and chronic supportive care; morbidity and mortality; and short- and long-term health and social
consequences for recovered people, their families, and communities. The need for epidemiological studies
is timely as jurisdictions move away from strict lockdowns and social (“physical”) distancing.

Epidemiologists typically undertake their studies in multidisciplinary teams composed of scientists from
diverse backgrounds such as virology, medicine, and public health. Multidisciplinary teams are needed to
help reduce the high levels of COVID-19 research waste,9 which have led to the retraction of numerous
published scientific papers, including articles on the effectiveness of masks for preventing SARS-CoV-2
spread,10 hydroxychloroquine or chloroquine with or without a macrolide for treating COVID-19,11 and the
association between angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers with in-
hospital deaths from COVID-19.12 Epidemiologists can communicate the prudence of waiting for well-
designed and executed studies as an alternative to basing clinical or policy decisions on incomplete or poor
evidence.

Epidemiologists can lead the design and conduct of rigorous community- or population-level surveillance
studies that characterize the prevalence of pre-symptomatic or asymptomatic SARS-CoV-2 infections and
subsequent health-related outcomes. To date, INEP knows of no coordinated international effort to
comprehensively research major SARS-CoV-2 transmission hotspots. In regions where SARS-CoV-2
diagnostic testing is limited due to infrastructure constraints, or targeted solely at high-risk groups such as
healthcare workers, epidemiologists can randomly sample individuals for testing in an effort to obtain
accurate prevalence data. Iceland has already done a population-level testing study using a three-pronged
recruitment strategy (targeted, random, and by invitation),11 and other nations are planning similar efforts.
Policy makers will hopefully be able to use the data from such studies to more rapidly identify strategies to2
forestall subsequent waves of SARS-CoV-2 infection, once scientists resolve issues about the performance
and interpretation of antibody tests.13

Carefully-conceived and well-conducted epidemiological research offers an antidote to misinformation and
disinformation about SARS-CoV-2 and COVID-19. Epidemiologists are needed more than ever to provide
unbiased evidence to counter conspiracy theories and false claims about the effectiveness of vaccines and
treatments.14 INEP calls on epidemiologists around the world to serve as voices of reason and moderation
against unnecessary hysteria and sensationalism about the pandemic—whether promoted through social
media or traditional media outlets such as radio, print, and television.15 Epidemiologists should also speak
out when necessary and provide unbiased evidence to refute xenophobia arising out of the pandemic.16 At
the same time, epidemiologists should support free and open discussion/debate, rather than censorship, as
the optimal means of engaging all relevant stakeholders in the formulation of policy.

Table 1 below lists a series of research priorities for epidemiologists during the pandemic. INEP encourages
epidemiologists from around the world to form multidisciplinary partnerships and tackle these priorities.

Table 1. Research Priorities for Epidemiologists during the SARS-CoV-2 and COVID-19 Pandemic

Immediate Priorities

1) Reduce morbidity and mortality during the COVID-19 pandemic.

a. What is the optimal means of defining a case (including sensitivity and specificity
of case definitions)?
b. Can we provide more meaningful metrics of area-based case-reporting, including
reporting delay, incubation-period delay, and testing-frequency adjusted incidence?
c. What environmental factors, e.g., air pollution, population density, are risks for
human SARS-CoV-2 infection acquisition and COVID-19 morbidity and mortality?
d. What is the role of underlying comorbid disease in human SARS-CoV-2 infection
acquisition and COVID-19 survival?
e. What genetic/biological/social factors may predispose people to severe COVID-19
symptomatology or death (e.g., sex, race/ethnicity)?
f. What behavioral interventions (e.g., physical activity, nutrition, smoking, and
alcohol consumption) are associated with improved survival and health-related
quality-of-life outcomes from COVID-19?
g. What factors are associated with pre-symptomatic and asymptomatic COVID-19
viral shedding?
h. How do environmental conditions alter exposure pathways and anatomic exposure
routes of SARS-CoV-2 transmission (e.g., nasopharyngeal droplet, airborne, fomite,
oral fecal, blood, sweat, other body fluids)?
i. What strategies can limit environmental transmission in high-risk settings (e.g.,
hospitals, intensive care units, seniors’ residences, long-term care and aged-care
facilities, correctional facilities, public transport)? This includes access to personal
protective equipment for persons who work in high-risk settings.
j. Does recovery from COVID-19 confer immunity to reinfection, or pose a risk of
more severe disease if re-infected13,17,18 with SARS-CoV-2? How long does the
immunity last? If re-infection does occur, then what is the nature of the subsequent
illness in terms of severity, symptomatology, and recovery time?3
k. What are the most effective and efficient methods for quarantining the close contacts
of persons with COVID-19, and for monitoring quarantine behavior?
l. What is the diagnostic accuracy of tests used for identifying active and past infection
with SARS-CoV-2 (e.g., sensitivity and specificity of RT-PCR tests and of
commercial antibody tests)?
m. What is the effectiveness and safety of proposed treatments for COVID-19? By
extension, what are the data about the role of medications and SARS-CoV-2
susceptibility?
n. What are potential long-term effects of experimental treatment regimens for
COVID-19?
o. Given observations that fecal shedding may persist beyond oral shedding of the virus
in some age groups,31 what is the role of virus transmission via fecal-oral routes?
What proportion of cases might be attributed to this route of transmission, and what
environmental settings are at most risk of fostering such transmission?

2) What is the efficacy and effectiveness of different vaccine candidates to prevent infection
from SARS-CoV-2? What is the role of host genome and possible disruption of
environmental exposures in vaccine response?

3) How do disease modelling approaches compare to actual events (e.g., comparability of
predicted and actual deaths over a certain time period)?

4) How can public health authorities establish nation-specific COVID-19 case registries that
respect privacy guidelines?

5) Are there reasonable alternatives to population-wide lockdowns and physical (social)
distancing policies?

a. What criteria/health indicators can be used to determine if jurisdictions should ease
or resume population-wide lockdowns and physical (social) distancing policies?
b. What are the alternatives to population-wide lockdowns and physical (“social”)
distancing, and what is the evidence for the efficacy/effectiveness of such
alternatives (e.g., mask wearing32)?
c. How can vulnerable groups such as senior citizens,33 low income recipients,34
racial/ethnic minorities,8 or substance abusers35 be protected from infection?

Intermediate and Longer-term Priorities

1) What are key factors in case under-reporting and case ascertainment differences between
countries?

2) What was the total of excess deaths during the pandemic period not caused by COVID-19?
What other medical conditions went untreated, what were the end results of this lack of
treatment, and how can we implement plans to avoid this problem in the future?

3) What public health policies most reduce the number of total infection rates and total death
rates from COVID-19 in different jurisdictions (e.g., mandatory versus optional use of
facemasks in public areas).

4) Identify the public health messages and messaging protocols that are most effective in
educating and incentivizing the general public to take preventive action against SARS-CoV-
2/COVID-19.4

5) Investigate the degree of rigour by which different jurisdictions handled case identification,
case isolation, quarantine of case contacts, and enforcement of quarantine. What were the
end results of these differences?

6) Assess the extent to which population-level lockdowns and physical (“social”) distancing
are effective.

a. What were the short- and long-term adverse health consequences of population-level
lockdowns and physical (social) distancing (e.g., depression, anxiety,36 escalation of
domestic violence,37 delays in immunization schedules for children,38 loss of
household income, switching to lower efficacy cancer therapies to redirect hospital
resources to COVID-1939)? How did these outcomes compare with the health
benefits of the policy?
b. In the event governments opt for population-level lockdowns and physical (social)
distancing policies in the future, what concomitant support systems or interventions
will be necessary to counteract the adverse consequences of social distancing,
especially with regard to vulnerable sub-groups of the population?

References
1. Question Bank [Internet]. Cochrane COVID Rapid Reviews. [cited 2020 Apr 20]. Available from:
https://covidrapidreviews.cochrane.org/search/site/
2. Government of Canada CI of HR. Notices - CIHR [Internet]. COVID-19 Clinical Epidemiology
Research Rapid Response. 2010 [cited 2020 Apr 20]. Available from: https://cihr-
irsc.gc.ca/e/42405.html#04_2020
3. Coronavirus (COVID-19) | About [Internet]. NICE. [cited 2020 Apr 20]. Available from:
https://www.nice.org.uk/covid-19
4. Coronavirus Disease 2019 (COVID-19): Information for NIH Applicants and Recipients of NIH
Funding | grants.nih.gov [Internet]. [cited 2020 Apr 20]. Available from:
https://grants.nih.gov/policy/natural-disasters/corona-virus.htm
5. Global Research on Coronavirus Disease (COVID-19) [Internet]. [cited 2020 May 11]. Available
from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-
coronavirus-2019-ncov
6. COVID-19 (2019 Novel Coronavirus) [Internet]. [cited 2020 May 11]. Available from:
https://www.cdc.gov/library/researchguides/2019NovelCoronavirus.html
7. Zimerman A. Evidence-Based Medicine: A Short History of a Modern Medical Movement. AMA J
Ethics. 2013;15:71–6.
8. Yancy CW. COVID-19 and African Americans. JAMA [Internet]. 2020 [cited 2020 Apr 15];
Available from: https://jamanetwork.com/journals/jama/fullarticle/2764789
9. Glasziou PP, Sanders S, Hoffmann T. Waste in Covid-19 Research. BMJ. 2020;369:m1847.
10. Oransky AI. Top Journal Retracts Study Claiming Masks Ineffective in Preventing COVID-19 Spread
– Retraction Watch [Internet]. 2020 [cited 2020 Jun 3]. Available from:
https://retractionwatch.com/2020/06/01/top-journal-retracts-study-claiming-masks-ineffective-in-
preventing-covid-19-spread/
11. Retraction—Hydroxychloroquine or Chloroquine with or without a Macrolide for Treatment of
COVID-19: A Multinational Registry Analysis [Internet]. The Lancet. 2020. Available from:
https://doi.org/10.1016/ S0140-6736(20)31324-6
12. Rubin EJ. Expression of Concern: Mehra MR et al. Cardiovascular Disease, Drug Therapy, and
Mortality in Covid-19 [Internet]. N Engl J Med. 2020. Available from:
https://doi.org/10.1056/NEJMoa2007621.5
13. Weiss SH, Wormser GP. COVID-19: Understanding the Science of Antibody Testing and Lessons
from the HIV Epidemic. Diagn Microbiol Infect Dis. 2020;115078. Available from:
https://doi.org/10.1016/j.diagmicrobio.2020.115078
14. Calisher C, Carroll D, Colwell R, Corley RB, Daszak P, Drosten C, et al. Statement in Support of the
Scientists, Public Health Professionals, and Medical Professionals of China Combatting COVID-19.
The Lancet. 2020;395:e42–3.
15. Garrett L. COVID-19: The Medium is the Message. The Lancet. 2020;395:942–3.
16. Devakumar D, Shannon G, Bhopal SS, Abubakar I. Racism and Discrimination in COVID-19
Responses. The Lancet. 2020;S0140673620307923.
17. Jiang S, Hillyer C, Du L. Neutralizing Antibodies against SARS-CoV-2 and Other Human
Coronaviruses. Trends Immunol. 2020;41:355–9.
18. Wan Y, Shang J, Sun S, Tai W, Chen J, Geng Q, et al. Molecular Mechanism for Antibody-Dependent
Enhancement of Coronavirus Entry. J Virol. 2020;94(5):e02015-19.