More than 16 million Americans had undiagnosed SARS-CoV-2 infections during first wave

Reviewed by Emily Henderson, B.Sc.Jun 23 2021

As many as 16.8 million Americans had undiagnosed SARS-CoV-2 infections - 5 times the rate of diagnosed infections - by the end of July of 2020, according to an analysis of antibodies from more than 8,000 previously undiagnosed adults collected during the pandemic's first wave.

The authors calculated that almost 5% of the undiagnosed U.S. population harbored SARS-CoV-2 antibodies, with the highest positivity rates among African Americans, those under the age of 45, urban dwellers, and women. The results suggest a larger spread of COVID-19 in the U.S. than originally suspected in previous reports.

SARS-CoV-2 can stealthily cause asymptomatic infections in some individuals, who can still spread the disease to others. This property has frustrated health authorities' efforts to track down the true number of infected people, especially during the pandemic's early stages in the spring and summer of 2020.

Here, Heather Kalish and colleagues posed survey questions to, and analyzed blood samples from, 8,058 undiagnosed adults reflecting the makeup of the U.S. population, which the team mostly gathered from early May to the end of July in 2020. They ensured a representative sample by using quota sampling with a much larger pool of more than 460,000 volunteers, allowing the scientists to make estimates about the general population.

Kalish et al. found that 304 of the participants harbored antibodies against the SARS-CoV-2 spike protein and its receptor binding domain, leading them to estimate that 4.6% of the U.S. population harbored undiagnosed infections.

The team also found differences in seropositivity across regions, gender, and ethnicity: rates were highest in the Mid-Atlantic (8.6%), in women (5.5%), and in African-Americans (14.2%), while lower in people working from home (3%) and in patients with chronic conditions such as heart disease. "Our findings have implications for understanding SARS-CoV-2 spread ... and prevalence in different communities and could have a potential impact on decisions involved in vaccine rollout," the authors conclude.