What can and what can not tell a study on antibodies to COVID-19
'09.05.2020'
Source: Inosmi.ru
Recently, tests for antibodies to COVID-19 have become very popular. Information about them is often perceived at face value and thoughtlessly disseminated. Scientists are sounding the alarm: people may feel a sense of false security, because it is still unknown whether the presence of antibodies saves from reinfection, writes "Inosmi" with reference to the American publication Scientific American.
Recently, dozens of antibody tests for a new coronavirus have become available. Preliminary results from studies of such serological tests in the United States and around the world have become a sensation in the media. Optimism about these tests may be the key to returning to normal, but experts say that reality is much more complicated, and much depends on how to use the results.
Antibody assays can help scientists understand the extent of COVID-19. But since the accuracy of the tests has its limitations, and in matters of immunity there is a lot of unknown, they give much less information about previous human infectious diseases and about protection against future infections.
“Right now, the focus is mainly on epidemiology,” said Professor Tara Smith, professor of epidemiology at Kent State University's College of Public Health. This approach involves trying to figure out the proportion of the population that has already been infected, although some people have not had any symptoms.
“This will allow us to better calculate the number of deaths and determine either how much more needs to be passed for collective immunity to emerge, or when a significant part of the population will be immune to the disease through vaccination and a previous infection,” Smith explains. “And it will allow us to study the duration of immunity.”
Mass serological examinations have already been performed in different parts of the United States, but the results are very different. If the estimates of positive antibody tests in New York are almost 25%, and in Chelsea, Massachusetts, 32%, then in the California districts of Los Angeles and Santa Clara, they are 2,8-5,6% and 2,8 % respectively.
These results confirm the experts' suspicions arising from a study of specific cases of asymptomatic infection: COVID-19 is much more widespread than data from hospitals show. But scientists criticized some of these studies, talking about the fallacy of the sampling methodology, possible statistics flaws, and that the results are announced at press conferences instead of subjecting them to expert evaluation and first published on specialized sites.
These problems of the methodology and the alleged lack of transparency are compounded by the fact that many analyzes do not meet the requirements. The numerous test systems that have flooded the market today have not been verified by third parties. And those that have received permission to use in emergency situations from the Office for Sanitary Control over the Quality of Food and Drug Administration may not be accurate enough when assessing the incidence beyond the foci of infection.
Johns Hopkins University Health Safety Center maintains and regularly updates a website listing the characteristics of many existing and ongoing serological tests for the SARS-CoV-2 virus that causes COVID-19. Experts recommend checking the tests during the studies involving at least 100 patients with positive test results and 100 with negative ones, the test results of which are confirmed by diagnostic tests and symptoms. Antibody tests available on the market have been tested and confirmed only in dozens of people, and only in individual cases there are more than a thousand such people. To date, the Health Safety Center has compiled a list of tests approved for research and individual use in the United States that detect antibodies in people with them with an accuracy of 82-100%. This accuracy is called sensitivity. And the ability to correctly detect antibodies only in those who have them is called specificity, and here the indicators range from 91 to 100%.
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At first glance, these are pretty good numbers. However, “the threshold is set by context,” says associate professor Sarah Cobey, who works on environmental and evolution issues at the University of Chicago.
“So if seroprevalence, or the proportion of people with antibodies to SARS-CoV-2, is three percent versus five, then this is a very good test,” she explains. - And if you are only trying to determine whether seroprevalence exceeds 50% or falls short of this indicator, then the test is not very good. But with COVID-19, no one falls into this category. ”
Such variability of acceptable tests is explained by the fact that in a population with a higher rate of spread of the disease or previous infections, true positive results (these are people with a positive test result, antibodies to the disease from a previous infection) and false negative results (people with a negative test result , but having antibodies) are more common. Meanwhile, among people with a lower prevalence of the disease, tests often give false-positive results.
In Santa Clara County, a preliminary antibody test study was concluded: its specificity is 99,5%. However, epidemiologist Trevor Bedford of Washington University tweeted that if the specificity of the test were 98,5%, that is, within the margin of error that the scientists determined, then all the “positive results” of the study could be false positive .
In part, these problems can be removed by constructing models that take into account such an error factor. However, an overestimation of the prevalence of COVID-19 can lead to an underestimation of deaths and hospitalization rates, or to excessive confidence in collective immunity. Currently, for the appearance of such immunity it is necessary that about 70% of the population become infected with the virus. There is no such indicator anywhere, even in foci like New York. And such errors can lead to decisions that adversely affect public health.
Further, a reassessment of the number of people with antibodies to SARS-CoV-2 can create an unreasonable sense of security regarding the diagnostic role that tests play. Since false-positive results are more common where incidence is low, Smith notes, “there is such a possibility that people will have a misconception about their antibody status. If they have a false-positive result, they may consider that they have received immunity and weaken individual protection measures, although in fact they have no immunity. ”
Experts warn that at this stage even the best tests for antibodies to SARS-CoV-2 at the individual level are of little use. More than four months have passed since doctors in Chinese Wuhan first discovered a new coronavirus that causes COVID-19, and scientists still do not understand how our immune system reacts to it. Studies are increasingly convincing that most infected people probably develop antibodies to the virus, but it is not yet clear whether these antibodies prevent re-infection, and for how long immunity is maintained.
“We are not aware of the natural course of the disease. We can only say that if a person has a good antibody test, and he trusts a result that is positive, it means that he really was infected, ”says Professor May Chu, an epidemiology professor at the University of Colorado School of Public Health. )
“We do not know whether these antibodies protect. And we won’t know about it for many more months until someone who is ill again becomes infected with the virus, and we will understand whether he is ill or not, ”continues Professor Chu, a member of the WHO expert group that deals with infection control and prevention the spread of the COVID-19 epidemic. On April 24, WHO published a scientific review warning of the inadmissibility of using so-called “immune passports” and “risk tolerance certificates”. There are reports that people give a positive result for tests for the virus and after recovery, although upon discharge from the hospital received a negative test result. But so far there is no evidence that this is a re-infection. Some experts believe that antibody tests will help determine whether such cases are the result of re-infection or “re-detection” caused by a clinical oversight.
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Scientists are trying to understand how a pandemic behaves in different countries of the world. However, anti-SARS-CoV-2 antibody assays are still under investigation. Now in the United States, nationwide studies are being conducted to collect samples from tens of thousands of people, and they will last another two years.
Opportunity for testing for active infection is unevenly distributed across the country. And antibody tests provide an opportunity to shed light on a situation where there are no resources to confirm active cases of the disease.
“It is imperative that different regions conduct their own serological tests to find out exactly how the transmission of infection occurs,” says Kobe. “This is the only way to adapt medical interventions to local conditions.”
