Increasing evidence suggests that COVID-19 was spreading in the United States for weeks, if not months, before it was widely recognized.

A study in Clinical Infectious Diseases points out that SARS-CoV-2 testing capacity was very limited in the United States at the start of the outbreak, from January through March, and, for the first 2 months, was mostly limited to symptomatic patients with a travel history. The result, according to Johns Hopkins Bloomberg School of Public Health–led authors, was “obscuring the picture of SARS-CoV-2 seeding and community transmission.”

In response, the study team set out to identify those with SARS-CoV-2 antibodies in the early weeks of the epidemic in the United States.

The All of Us study, funding by the National Institutes of Health, included participants in all 50 states who provided blood specimens from January 2 to March 18, 2020. Seropositivity was determined by SARS-CoV-2 immunoglobulin G (IgG) antibodies on the Abbott Architect SARS-CoV-2 IgG ELISA and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm, which had high sensitivity of from 90% to 100%.

“Antibody testing of blood samples helps us better understand the spread of SARS-CoV-2 in the U.S. in the early days of the U.S. epidemic, when testing was restricted and public health officials could not see that the virus had already spread outside of recognized initial points of entry,” said lead author Keri N. Althoff, PhD, associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore. “This study also demonstrates the importance of using multiple serology platforms, as recommended by the CDC.”

Those antibodies do not appear until about 2 weeks after a person has been infected, which signals that those participants testing positive were exposed to the virus at least several weeks before their sample was taken.

Researchers determined that nine of the 24,079 study participants with blood specimens from January 2 to March 18 were seropositive; seven of those were found to have been seropositive before the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi; the first positive samples came from participants in Illinois and Massachusetts on January 7 and 8, 2020, the study advises.

“Our findings indicate SARS-CoV-2 infections weeks prior to the first recognized cases in 5 U.S. states,” the authors write.

“This study allows us to uncover more information about the beginning of the U.S. epidemic and highlights the real-world value of longitudinal research in understanding dynamics of emerging diseases like COVID-19,” added coauthor Josh Denny, MD, MS, chief executive officer of All of Us. “Our participants come from diverse communities across the U.S. and give generously of themselves to drive a wide range of biomedical discoveries, which are vital for informing public health strategies and preparedness.”

An NIH press release points out that the findings bolster those from a CDC study, which also determined that SARS-CoV-2 was present in the United States as far back as December 2019.

The NIH also emphasizes that participants were from outside two major urban hotspots—Seattle and New York—which are thought to be first points of entry for the virus in this country.

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