NIH-led study finds COVID-19 antibodies in 4.6% of those never diagnosed

By July of 2020, 16.8 million people in the US had COVID-19 -- and didn’t know it, according to a study led by the National Institutes of Health (NIH) and published ahead of peer review by medRxiv on January 31.

"We thought there were 3 million cases by summer. There were actually 20 million," Kaitlyn Sadtler, PhD, Chief of the Section for Immunoengineering at the National Institute of Biomedical Imaging and Bioengineering and lead author of the NIH-funded study, said on Twitter.

The study team included scientists from the National Institute of Allergy and Infections Diseases, the University of Pittsburgh, and the University of Alabama Birmingham. Those three sites recruited volunteers who never had a positive COVID-19 diagnosis and enrolled 11,283. More than 9,000 blood samples were analyzed for COVDI-19 antibodies, and the prevalence of those antibodies (seroprevalence) was estimated using a weighted analysis to reflect the US population.

The researchers found that 4.6% of study participants who never knew they had COVID-19 were actually seropositive, showing that they had been infected.

Geographic areas with higher levels of undiagnosed seroprevalence were correlated with areas that had early severe outbreaks in the spring, whereas those subject to severe fall waves had very low undiagnosed seroprevalence by the summer of 2020. The largest burden of undiagnosed infections was in Black/African Americans (14.2%). Hispanic ethnicity, younger age (18-44 yrs), female sex, and urban living all had undiagnosed seroprevalence estimates above the national average.

People who reported pre-existing health conditions, such as cardiovascular disease, asthma, pulmonary disease, or diabetes, had a lower undiagnosed seroprevalence. This could be because of a variety of factors, including the tendency of COVID-19 to present more severely in patients with comorbidities, or behavioral changes associated with avoiding exposure to COVID-19.

Individuals who reported having flu or pneumonia vaccinations also had lower undiagnosed seroprevalence rates, possibly due to increased adherence to public health guidelines such as masking and social distancing. Although those with a reported COVID-19 exposure (a lower number of participants) had higher levels of undiagnosed seroprevalence, there was no correlation with reports of being sick, suggesting an important role for asymptomatic transmission.

"These data suggest a higher level of infection-induced immunity exists in the population and the size of those with this immunity is even greater now, as the virus continued to spread in the months since this study was performed," the authors wrote. "Further long-term studies of immunity in the population will be necessary to further understand durability of response to the vaccine versus infection, how infection-induced immunity impacts vaccine response and performance, and if herd immunity can play a role in controlling SARS-CoV-2 spread."

Read the study: https://www.medrxiv.org/content/10.1101/2021.01.27.21250570v1