The Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota reported a study published in JAMA Internal Medicine of the analysis of serum samples collected as part of routine COVID-19 testing from 10 US sites from March 23 to May 12, suggesting that, while most people had not been infected, at least 10 times more people were probably infected than previously reported.
The study stated that, “In this cross-sectional study of 16,025 residual clinical specimens, estimates of the proportion of persons with detectable SARS-CoV-2 antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). Six to 24 times more infections were estimated per site with seroprevalence than with coronavirus disease 2019 (COVID-19) case report data. For most sites, it is likely that greater than 10 times more SARS-CoV-2 infections occurred than the number of reported COVID-19 cases; most persons in each site, however, likely had no detectable SARS-CoV-2 antibodies.”
Two other studies, published in Morbidity and Mortality Weekly Report, showed low antibody seroprevalence levels in Indiana and Georgia.
“In this metropolitan Atlanta survey, an estimated one half of seropositive persons recalled having had a COVID-19–compatible illness, approximately one third sought medical care for the illness, and even fewer had a test for SARS-CoV-2 infection. These findings highlight that many SARS-CoV-2 infections would have been missed by case-based surveillance, which requires receiving medical care in the health care system or a test for SARS-CoV-2, and by syndromic surveillance, which relies on symptomatic illness. As testing practices change during the course of the pandemic, this pattern, reflecting findings at the end of April, might also change.”
The JAMA Internal Medicine study, led by researchers from the Centers for Disease Control and Prevention, is the first known US multistate and city-level serosurveillance study. It produced adjusted estimates of the prevalence of seroreactivity against SARS-CoV-2, the virus that causes COVID-19, ranging from 1.0% in the San Francisco Bay area to 6.9% in New York City.
Sampling was done at sites in California, Connecticut, Florida, Louisiana, Minnesota, Missouri, New York, Pennsylvania, Utah, and Washington state. The vast majority of people at each site had no detectable coronavirus antibodies, the authors noted, adding that it is not yet known whether or how long antibodies to COVID-19 confer future immunity to it.
The extrapolated number of infections at each site ranged from 6 times (Connecticut) to 24 times (Missouri) the number of reported cases. In Connecticut, Florida, Louisiana, Missouri, New York, Utah, and Washington, COVID-19 infections were an estimated 10 times higher than the number reported. The seroprevalence estimates likely reflected infections that occurred at least 1 or 2 weeks before specimen collection, the authors said.
The study authors said their findings show that most people in 10 diverse geographic areas of the United States had not been infected with COVID-19 as of May. "The estimated number of infections, however, was much greater than the number of reported cases in all sites," they wrote. "The findings may reflect the number of persons who had mild or no illness or who did not seek medical care or undergo testing but who still may have contributed to ongoing virus transmission in the population."
An additional commentary in Jama Internal Medicine, by Tyler Brown, MD, and Rochelle Walensky, MD, MPH, of Massachusetts General Hospital in Boston, cautioned that convenience samples are inherently biased and that the populations studied are likely not representative of a usual pre-pandemic cohort because the study data-collection periods overlapped with stay-at-home orders, when most clinic appointments and hospital procedures were deferred, and occurred during different parts of local epidemics.
But they said that the study proves that achieving 60% to 70% seroprevalence, or herd immunity, is unlikely to happen any time soon and should disprove beliefs that risky practices such as "COVID parties" are a good way to achieve that goal.
"The results reported by Havers et al also challenge the idea that there is a trade-off between implementing a prompt, effective public health response to the epidemic and acquiring higher levels of population-level immunity that might be protective in the future," Brown and Walensky wrote. "As the authors underscore, the vast majority of individuals in all 10 study locations had no serologic evidence of prior SARS-CoV-2 infection, both in locations with relatively contained epidemics (San Francisco) and in those that were affected most heavily (New York)."
Active surveillance, they added, is urgently needed to identify the large numbers of coronavirus infections circulating undetected in the community because of massive testing shortfalls. And focused studies, stratified according to potential determinants of exposure risk, could identify the factors behind differences in infection prevalence across geographic areas.
"Scientists, public health workers, and policy makers will be tasked with extracting meaningful, actionable findings demonstrated in these studies, many that may rely on imperfect or even flawed data sources," the commentary authors wrote. "This is no easy task, much uncertainty will likely remain, and these data will only be influential in an environment of evidence-based, scientifically driven public health leadership."
The Johns Hopkins Coronavirus map reports 14,976,573 global cases this morning with 617,297 deaths. The US is reporting 3,902,377 cases and 142,090 deaths.
