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Volume 26, Number 9—September 2020

Seroepidemiologic Study Designs for Determining SARS-COV-2 Transmission and Immunity

Hannah ClaphamComments to Author , James Hay1, Isobel Routledge1, Saki Takahashi1, Marc Choisy2, Derek Cummings2, Bryan Grenfell2, C. Jessica E. Metcalf2, Michael Mina2, Isabel Rodriguez Barraquer2, Henrik Salje2, and Clarence C. Tam2
Author affiliations: National University of Singapore Saw Swee Hock School of Public Health, Singapore (H. Clapham, C.C. Tam); Harvard University T.H. Chan School of Public Health, Boston, Massachusetts, USA (J. Hay, M. Mina); University of California San Francisco EPPIcenter Program, San Francisco, California, USA (I. Routledge, S. Takahashi, I. Rodriguez-Barraquer); University of California San Francisco Department of Medicine, San Francisco (I. Routledge, S. Takahashi, I. Rodriguez-Barraquer); Oxford University Clinical Research Unit–Vietnam, Ho Chi Minh City, Vietnam (M. Choisy); University of Florida Department of Biology, Gainesville, Florida, USA (D. Cummings); Princeton University, Princeton, New Jersey, USA (C.J.E. Metcalf, B. Grenfell); University of Cambridge, Cambridge, UK (H. Salje); London School of Hygiene and Tropical Medicine (C.C. Tam)

Main Article


Describing different study designs, questions they could answer, and issues with study design and execution during the coronavirus disease pandemic

Study type Brief description Questions study could answer Issues with interpretation and representativeness Issues with conducting during a pandemic
A sample of the population has serum samples collected at 1 time point
Background cross-reactivity (if started before pandemic); current proportion of population that have been infected; proportion of population that is immune (if a correlate of protection defined); infection fatality ratio (with information on cases or deaths in the same population)
For the different modes of collection (e.g., blood banks, residual sera, and volunteers), different issues can bias the sample included in the study that must be assessed
Blood banks might have fewer participants, residual sera studies in hospitals might have fewer samples or over representation of severe acute respiratory syndrome coronavirus 2 infections
The same persons are followed up over time, with serum samples collected at regular intervals, and information on disease in intervening periods
Background cross-reactivity (if started before pandemic); ratio of asymptomatic to symptomatic infections; waning of antibody levels, correlates, and duration of protection; changes in infection dynamics over time
Attrition can make analysis and interpretation difficult, biases in which participants are retained across sampling rounds
Challenges in collecting and continuing cohort during outbreak; attrition
Targeted populations Populations with particularly high exposures, such as those around index patients or healthcare workers, have serum samples taken either cross-sectionally or in a targeted cohort Attack rates; ratio of asymptomatic to symptomatic infections; proportion of population infected, correlates, and duration of protection Targeted populations because healthcare workers might have different infection exposure rates and intensity from the general population Potentially logistically difficult to collect samples in household studies

Main Article

1These first authors contributed equally to this article.

2These authors contributed equally to this article.

Page created: June 02, 2020
Page updated: August 18, 2020
Page reviewed: August 18, 2020
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