Some people may have been infected with the novel coronavirus as early as December 13, more than a month before the US Centers for Disease Control and Prevention confirmed the first case of the virus, according to a study published online November 30 in Clinical Infectious Diseases, in which researchers analyzed blood samples from American Red Cross donations. The findings provide further evidence that the virus was spreading around the world well before public health officials and researchers thought it had started circulating.

The Red Cross had originally collected the blood samples to test for exposure to mosquito-borne illnesses such as West Nile virus and the study authors used them to test for antibodies against SARS-CoV-2, Susan Stramer, an American Red Cross virologist and a coauthor of the paper, tells The New York Times

Among the 7,389 samples, 106 had SARS-CoV-2 antibodies,...

Of 90 samples the researchers could perform follow-up tests on, 84 showed some evidence of antibodies blocking SARS-CoV-2 from binding to ACE2, a receptor the coronavirus uses to enter host cells.

Positive SARS-CoV-2 antibody tests suggest a prior COVID-19 infection, but they do not provide definitive proof, as prior exposure to other coronaviruses—some of which can cause a common cold—can produce a false-positive result. The authors conclude that it is unlikely that all 84 samples represent false positives, and therefore at least some reflect COVID-19 infections in December or early January.

Even though the authors tried to measure antibodies that were specific to SARS-CoV-2, cross-reactivity with other coronaviruses can’t be ruled out, George Rutherford, an epidemiologist at the University of California, San Francisco, who was not affiliated with the study, tells Live Science. He also notes that even if these results show actual COVID-19 infections, the researchers cannot determine where the participants acquired the infection—some blood donors could have recently traveled to China and became infected there, for example.

University of Washington epidemiologist Trevor Bedford, who has been using genetics to understand the timing and location of SARS-CoV-2 spread and was not involved in the study, writes in a Twitter thread that seasonal coronaviruses tend to circulate more often in the winter. He adds that antibody concentrations are typically higher in those recently infected compared to random healthy adults, suggesting that there could be a high false positive rate. Even if the results are accurate, then by extrapolation that would mean there were millions of infections in the general US population, which would have been accompanied by a higher excess death rate, he writes, something that wasn’t observed until March.

To better understand how often false positives occur, the researchers will look at blood samples from prior years to see whether they, as expected, would not show antibodies for SARS-CoV-2, Stramer tells the Times.

“We’re looking at the echoes of somebody’s infection,” Johns Hopkins Center for Health Security immunologist Gigi Gronvall, who was not affiliated with the study, tells USA Today. “I think we have pretty high expectations for the immediacy of our data and . . . the origin of diseases tends to be more murky and require months and years of investigation.”

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