Antibodies and SARS-CoV-2 infections: better

The two FDA-issued approvals for the COVID-19 vaccine are based on clear data that limit infection with the SARS-CoV-2 virus and ensure that subsequent cases are mild. Studies have also shown that vaccines trigger the development of virus-specific antibodies. But strangely, we don’t have the right data for the obvious question. Is there a causal relationship between the two? In other words, it has not been determined whether the production of anti-SARS-CoV-2 antibody is a necessary step to provide protection, or how long that protection will last.

There have been some small studies suggesting answers to these important questions, but significant uncertainty remains. Currently, a large study from Oxford University Hospital clearly shows that high levels of antibodies are protective. However, even with 12,500 participants, this survey does not rule out uncertainty.

Good news

To get some good numbers, Oxford University Hospital tested all of its staff of healthcare professionals for both the presence of viral RNA and antibodies that indicate past exposure to the virus. Following the initial test, all staff had the option of retesting the presence of the virus every two weeks and retesting the antibody every two months. Testing began in April, when the first wave of infection was still occurring, and continued until the end of November, when the second wave was still being built. Many of the hospital staff were so busy that the follow-up test took more than two weeks, but the hospital was able to track more than 12,500 people.

Already at the beginning of the study, 1,265 people were infected with the virus. Many of them experienced exposure or symptoms before the test became widespread in the United Kingdom, so it can be inferred that they were infected only based on the presence of antibodies.

During the course of the study, 225 eventually tested positive, with just under half of those positive results coming from asymptomatic cases. Most of those new cases were nearing the end of the study. A total of two of these people were among those who had antibodies to the virus during the initial test, suggesting that they had re-infected. In other words, the percentage of health care workers was generally 1.1 per 10,000 days of risk during the study period. The percentage of people who tested positive for antibodies was 0.13 per 10,000 days of risk. Both of these repeated infections were asymptomatic.

We’ll discuss these two cases later, but take a moment to focus on the good news. The antibody test used here does not generate a binary yes-no answer. Instead, they are quantitative and measure the level of antibodies against a particular target. Or, in this case, there are two targets because researchers have measured antibodies against both the peplomer protein on the surface of the virus and the protein embedded in the membrane surrounding the genetic material of the virus.

In both cases, there was a strong inverse relationship. The higher the level of antibodies present, the less likely it is that someone will be infected. This was also true for antibodies against both target proteins. This suggests that antibodies are directly involved in reducing the risk of infection or are clearly correlated with some. This also provides evidence that immunity persists for at least that period, as the highest risk occurred approximately 6 months after most people in the study were first exposed.

There are many warnings

If you pay attention there, you may discover potential problems. The fact that antibody levels correlate with risk of infection means that there is an intermediate state. One such condition occurs when some protection is obtained without high levels of antibodies. This is definitely the case for this data. To get the “two reinfections only” number, the author had to choose an antibody level threshold to indicate previously infected.

Below that threshold, it is not considered previously infected, but may have antibodies that react with the SARS-CoV-2 protein. This may be due to an early infection that caused a weak immune response, or to an infection with a related virus (such as a virus that causes the symptoms of a cold), or by chance. Therefore, it is possible that the majority of the study population actually experienced previous infections.

Behind the scenes, false positive testing is almost inevitable, even with the best available equipment. With 12,500 participants, both “reinfections” seen here could simply be the result of a false-positive antibody test. RNA-based tests have similar problems, which also produce false positives and false negatives. Researchers pointed out that one potential reinfection case was tested positive and then two negative tests were done in the next few days, suggesting that the first case was a false positive. doing.

Finally, on average, participants were screened for viral RNA every 10 weeks. Between these gaps, there is certainly time for asymptomatic infections to start and end without approaching the test kit.

So, if you take a closer look at the details, there are enough questions left to easily convince us that we really don’t know anything. But it will miss the forest by focusing on some stray trees. Overall, the more antibodies that are produced, the more likely it is that immunity to reinfection will increase (although it is not known if the antibodies themselves produce this immunity).And that protection continues at least 6 months after the first infection.

With a few exceptions, it is a precursor to approved vaccines and also provokes an immune response that contains significant levels of antibodies. And in the long run, these results should help us to get a clearer picture of what SARS-CoV-2 immunity looks like.

New England Journal of Medicine, 2020. DOI: 10.1056 / NEJMoa2034545 (((About DOI).