An editorial in JAMA: Serosurveillance and the COVID-19 Epidemic in the US: Undetected, Uncertain, and Out of Control | Infectious Diseases. Excerpt:
The true extent of the coronavirus disease 2019 (COVID-19) epidemic in the US is unknown. The 3.4 million confirmed cases reported (as of July 15, 2020) likely represent only a fraction of all the infections that have occurred in the US thus far. Limited laboratory capacity and restrictive testing guidelines early in the epidemic resulted in large numbers of undetected incident infections. Approximately 40% of all SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infections are thought to be asymptomatic, and active surveillance for infections without symptoms is limited even now, nearly 5 months after the first COVID-19 cases were reported in Seattle and Chicago.
The true cumulative incidence of infection—a basic but critically important measurement—remains uncertain at a time when communities nationwide are struggling to navigate an ongoing, unprecedented public health emergency, and while apprehensions about the near-term and long-term trajectories of the epidemic loom large.
The study by Havers et al, published in JAMA Internal Medicine, reports the first multisite state- and city-level serosurveillance data on SARS-CoV-2 infection in the US; regions spanned from New York to Washington State and from Minnesota to Utah. In a cross-sectional study that tested residual sera from clinical blood samples that had been obtained for routine testing from March 23 through May 12, 2020, from 16 025 persons from 10 different sites across the country, the authors report estimates for the proportion of individuals with prior SARS-CoV-2 infection (adjusted for performance characteristics of serological testing) ranging between 1.0% in San Francisco and 6.9% in New York City. The estimated total number of infections (extrapolated from the measured proportion of individuals with positive SARS-CoV-2 serologies) was between 6- and 24-fold higher than the number of confirmed COVID-19 cases reported in each location prior to the study.
Responding to the urgent need for data tracking the extent of the COVID-19 epidemic, epidemiologists, medical researchers, and public health officials have in recent months advanced an array of research efforts seeking to measure the cumulative incidence of COVID-19 via serologic evidence of prior infection. These serosurveillance efforts, many implemented as rapid pilot studies using unstructured or convenience sampling strategies, have nonetheless yielded some important, early, and actionable findings.
However, these studies are also challenging to interpret because of the limited reliability of some commercially available SARS-CoV-2 serology testing platforms and the limitations inherent to convenience sampling. Convenience sampling, although expedient and logistically less difficult than structured sampling, has numerous inherent biases, limiting generalizability. Virtually all of the early serologic studies have been narrow in scope, focused on specific geographic catchment areas or local cohorts captured via unrestricted, “walk-up” enrollment.
Havers et al provide a substantial step forward in this rapidly changing landscape and an important reference point for contextualizing the profusion of SARS-CoV-2 serosurveillance studies anticipated in coming months. The authors comprehensively describe their data sources, including detailed maps on the geographic distribution of samples obtained in each study location and timelines comparing when sample collection occurred with respect to the epidemic trajectory in each location. This transparent approach provides important information for understanding these results in the context of the shortcomings of any seroprevalence study.