What COVID-19 antibody tests can and cannot tell us

Dozens of antibody tests for the new coronavirus have become available in recent weeks. And the first results of studies of these serological tests in the United States and around the world made headlines. Despite optimism that these tests could become the key to getting back to normal life, experts say the reality is complicated and depends on how the results are used.

Antibody tests could help scientists understand the extent of the spread of COVID-19 in populations. Due to limitations in the accuracy of the tests and a plethora of unknowns about immunity itself, however, they are less informative about an individual’s past exposure or protection from future infection.

“Right now, the focus is mostly on epidemiology,” says Tara Smith, professor of epidemiology at Kent State University College of Public Health. This approach consists of trying to determine the percentage of the population that has ever been infected even if some individuals have never exhibited symptoms. “This will allow us to better calculate the death rate and determine how far we still have to go to reach [infection] levels that would put us in the range of herd immunity, ”or when a large part of a population has become immune to a disease due to a vaccination or past infection, she said. “It will also allow us to start looking at the duration of immunity. “

Serologic surveys have already been carried out in communities across the United States, and their results vary widely. Estimates of the prevalence of positive antibodies range from nearly 25% in New York City and 32% in Chelsea, Mass., To between 2.8 and 5.6% in Los Angeles County and 2.8% in County of Santa Clara, California.

These results corroborate what experts already suspected based on case studies of asymptomatic transmission: COVID-19 is much more prevalent than hospital data suggests. But several of the studies have been criticized by scientists, who have raised red flags about sampling methods, potentially flawed statistics, and results that are first announced in press releases rather than studies. peer reviewed or even preprint.

These methodological issues and the perceived lack of transparency are exacerbated by the pervasiveness of substandard testing. Many tests that are currently flooding the market have not been verified by third parties. And even those who have received emergency use clearance from the U.S. Food and Drug Administration might not be specific enough to assess disease prevalence levels outside of hot spots.

The Johns Hopkins Center for Health Security maintains and regularly updates a website that lists the main features of many serological tests for SARS-CoV-2, the virus that causes COVID-19, in the market and in development. Experts recommend that the tests be validated in studies that include at least 100 positive and negative patients whose infection status is confirmed against a benchmark such as diagnostic test results and symptoms. Antibody tests currently on the market have been validated in samples ranging from just a few dozen individuals to over 1,000. At the time of this writing, the Center for Health Security lists tests approved for research or individual use in the United States that accurately detect antibodies in people who have them – a statistic known as sensitivity – between 82 and 100 percent of the time. Their ability to correctly identify antibodies only in those who actually have them – known as specificity – ranges from 91 to 100 percent.

At first glance, these numbers look pretty good. But “the threshold is set by the context,” says Sarah Cobey, associate professor of ecology and evolution at the University of Chicago. “So if the seroprevalence,” or the proportion of the community that has antibodies to SARS-CoV-2, “is 3% versus 5%, you must have an extremely good test” to tell it apart, she said. . “If you are [only] by trying to identify if the prevalence is above 50% or below 50%, you can get away with perhaps a worse test. But no one is in this category [with COVID-19]. “

This variability in what constitutes an acceptable test results from the fact that in populations with a higher prevalence of a disease or with previous exposure to it, true positives (individuals who test positive and have antibodies against it). disease from a previous infection) and false negatives (those that test negative but actually have antibodies) are more common. Meanwhile, in low prevalence populations, tests are more likely to give false positives.

Credit: Amanda Montañez

The preprint study on an antibody test in Santa Clara County claimed it had a specificity of 99.5%. But University of Washington epidemiologist Trevor Bedford argued in a Twitter feed that if this test had instead a specificity of 98.5% – well within the range of possible uncertainty defined by the researchers – all the “positive results” of the study could have been false positives.

Some of these concerns can be managed by creating models that take into account the uncertainty. But overestimates of the spread of COVID-19 could lead to underestimates of death and hospitalization rates – or over-reliance on herd immunity. It is currently believed that such immunity requires about 70% of the population to have been exposed, a rate that even hot spots such as New York are likely far from close. Each of these mistakes could, in turn, lead to policies that are harmful to public health.

Additionally, overestimating the prevalence of people with SARS-CoV-2 antibodies could create an unwarranted sense of security about the diagnostic role that tests can play. As false positives are more common in places with low disease prevalence, Smith notes, “it is possible that individuals are misled about their position. [antibody] status. If they are false positive, they may believe they are immune when they are not and may relax protective measures. “

At this point, experts warn that even the best SARS-CoV-2 antibody tests are of little use on an individual level. More than four months after doctors in Wuhan, China first identified the novel coronavirus that causes COVID-19, scientists are still scrambling to understand how our immune system responds to it. Although research increasingly shows that most people who are infected are likely to produce antibodies against the virus, it is not yet clear whether these antibodies prevent reinfection or how long the immunity will last.

“We don’t know nature [course] of disease. All we can do is [say] that if you have a good [antibody] test, and you trust the result, and you’re positive, you’ve been exposed, ”says May Chu, clinical professor of epidemiology at the Colorado School of Public Health. “We don’t know if [those antibodies are] protective. And we won’t know for months, until someone else who was infected before is exposed to the virus again, and we will see if they get sick or not, ”said Chu, who is also a member of an expert from the World Health Organization. group focused on infection control and prevention for the COVID-19 outbreak. In fact, on April 24, the WHO released a science note explicitly warning against the use of so-called “immunity passports” or “risk-free certificates”. There have been a few reports of individuals testing positive for the virus after recovering and testing negative. But it has not been shown that they were re-infected. Some experts believe that antibody tests could help determine whether such cases are the result of reinfection or “redetection” caused by clinical relapse.

As scientists strive to understand how the pandemic is unfolding in different populations around the world, antibody testing against SARS-CoV-2 remains largely in the field of research. National surveys currently underway aim to collect samples from tens of thousands of people across the United States over the next two years.

The capacity to screen for active infections remains uneven across the country. And antibody tests provide an opportunity to shed light on the situation in places that have not had the resources to confirm active cases. “It will be extremely important that the different regions make their own [serological] surveys to pinpoint the exact extent of transmission, ”Cobey explains. “This is how you tailor interventions to the local situation. “

Learn more about the coronavirus outbreak from Scientific American here, and read coverage from our international magazine network here.

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