IIn the early days of the U.S. COVID-19 pandemic, officials focused limited testing capacity on symptomatic individuals who had recently traveled to or in close contact with someone who had traveled to locations with confirmed outbreaks of SARS-CoV-2 stood. A year later, it is clear that some virus transmission – perhaps up to 50 percent – is from presymptomatic or asymptomatic individuals, making it difficult to trace the transmission. In a study published in Clinical Infectious Diseases On June 15, researchers analyzed blood drawn between January 2 and March 18, 2020 and found antibodies to SARS-CoV-2 in samples from nine people in five US states, meaning the virus is likely to end Was present in the United States in 2019.
“We suspected there were likely cases that preceded those diagnosed and confirmed. This strongly suggests that there were likely multiple exposures prior to these initial cases, ”said Ashley St. John, an infectious disease researcher at Duke-NUS Medical School in Singapore who was not involved in the study. The results also suggest that “we can probably use serology in a similar way to find potentially even earlier exposures”.
In 2018, researchers from the National Institutes of Health and their staff in the United States began recruiting volunteers for the All of Us research program on Medicine Individual. The study therefore hiked on and collected the medical histories and blood samples of participants in the United States in early 2020 when SARS-CoV-2 emerged.
When public health closings began and recruitment and testing for longitudinal studies paused, Keri Althoff, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health, and her colleagues on the All of Us team spoke to see if they were looking at previously collected samples could whether there were antibodies targeting SARS-CoV-2. This line of investigation could “help us piece together the puzzle about the early days because that can help us understand where we can improve in preparing for future outbreaks,” she says.
Researchers across the country were developing tests to detect these antibodies at the same time. So the All of Us team partnered with a group from Quest Diagnostics and sent samples to their clinical laboratory for antibody testing. They requested two tests for each sample: one for antibodies targeting the protein surrounding the SARS-CoV-2 genome and one for antibodies targeting the viral spike protein. Of the 24,079 people who gave blood samples between January 2 and March 18, 2020, 147 were positive for antibodies directed against the nucleocapsid. Only nine participants tested positive for antibodies in both tests.
The earliest positive sample – from a participant in Illinois, taken on January 7th – was collected more than two weeks before the first official case report in the state on January 24th. The researchers also found SARS-CoV-2 antibodies in people from Massachusetts, Wisconsin, Pennsylvania, and Mississippi in samples collected before those states had official cases.
“On average, it takes about two weeks for [immunoglobulin G] Antibodies to be detectable. . . So now we’re talking about a possible infection on December 24th or even before that, ”explains Althoff. She adds that the results match the results of a November 2020 study conducted by researchers from the Centers for Disease Control that tested SARS-CoV-2 antibodies in donor blood in December 2019 and January 2020 in California, Connecticut, Iowa, Massachusetts, have found, confirm and expand Michigan, Oregon, Rhode Island, Washington and Wisconsin.
“That there were some cases of COVID-19 before the documented cases [is] a reasonable conclusion as we are unlikely to have discovered the very first case in many of these locations, ”says Saahir Khan, a clinician and scientist at the University of California, Irvine, who was not involved in the work. Since the authors found a very small number of antibody-positive people in this relatively large sample they tested, he adds, it’s possible that the number of antibody-positives they found here weren’t actually positive are.
“If you have a very low prevalence, you have to deal with false positive results,” Althoff admits, but the sequential testing strategy of two positive results, the subsequent quantification of the antibodies in these samples and the simulation models that the researchers tried that Healthcare use to predict cases and deaths all suggest that the outcomes are very unlikely to be due to errors.
Other evidence they may pursue in the future is, according to St. John, neutralization assays, in which researchers mix antibody-positive serum or antibodies isolated from blood samples with live viruses and see what happens. The result is “very suggestive, but a neutralization test would have really sealed the deal for me,” she says.
What the results mean for the origins of SARS-CoV-2 in the USA: “It is important to remember that this is a very small sample of what is happening in the country at this time,” explains St. John. “There could be a lot more infections than we expected,” she adds. “It’s kind of a wake-up call that we need to improve our surveillance to detect these types of emerging infectious diseases so we can see more of the early cases because it really shows that we have a little bit of a glimpse of what happened”. “