About antibodies to COVID-19: simple and comprehensive. Op-Ed by Ala Tocarciuc

"In this way, antibody tests can help scientists and public health experts better understand the epidemiology of people and populations at higher risk of contracting COVID-19."
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Almost all immunocompetent people develop an adaptive immune response after contracting COVID-19, which includes humoral and cellular immunity, or B and T, cellular mediated immunity.

Our knowledge of the immune response to COVID-19 is currently incomplete, however the science is progressing rapidly.

In humans, the humoral immune response includes antibodies directed against the proteins S and N. Protein S or spike protein contains two subunits, S1 and S2. Sub-unit S1 contains RBD, a kind of peaks that mediate the binding of the virus to sensitive cells. RBD is the main target for neutralizing antibodies. Most tests designed to measure antibody levels after vaccination will specifically measure the titer for RBD in the S1 subunit.

Recently, there have been many questions about antibodies. I tried to collect and answer some of them here.

What antibody titer in COVID-19 is considered normal and why?

There is no concept of a "normal titer" of antibodies. Each test kit has a reference scale according to which the result is interpreted. In different tests, the scale of the numbers is different, and it is usually indicated in the sheet with the measurement results. The results are interpreted according to the used reference control scale.

If antibodies are detected but the person has not been vaccinated or has not been sick (had no symptoms of the disease), how can such a result be interpreted?

If a person has antibodies against COVID-19 but was not previously tested positive for the virus or given a vaccine, it is assumed that the person has developed an asymptomatic disease that has produced antibodies.

If a person has been vaccinated but has no antibodies either in the first month or 3 or 6 months after vaccination. How do we interpret that?

Antibody testing is not currently recommended either to assess immunity to COVID-19 after vaccination or to assess the need for vaccination in an unvaccinated person. Because vaccines induce antibodies against specific targets of viral proteins, serological test results may be negative in people without a previous history of natural infection, if the used test does not detect neutralizing antibodies induced by the vaccine.

If a vaccinated person has been tested for antibodies and the result is negative, there may be several interpretations. First, as mentioned above, not all modern antibody tests detect RBD in the S1 subunit.

If the test turns out to be negative, it is likely that the antibody test should be repeated with other, more specific tests. Secondly, it's sometimes possible that there's no humoral immune response. In these situations, a test may be done to determine the cellular immune response.

What is the medical and financial relevance of antibody test analysis?

Currently, there are no international or national recommendations for mandatory antibody testing. For these reasons, in most cases, the costs of these tests are not covered by insurers. However, the U.S. and other countries have published temporary guidelines explaining the use of antibody tests for research or epidemiological purposes. In the case of clinical trials, the costs of tests are usually covered by the study sponsors.

Why is the vaccination certificate valid only for 1 year?

There is no maximum validity period for vaccination certificates, as this will depend on new scientific evidence regarding the duration of protection provided by different vaccines.

In the EU, however, there are rules for coordinating travel measures that include standard test validity periods: 72 hours for PCR tests and, if adopted by the Member State concerned, 48 hours for rapid antigenic tests.

The rules also apply some basic principles, such as that the maximum validity of a certificate of recovery is 180 days.

Later, these principles can be adjusted based on new scientific evidence.

After 1 year, do I need to be revaccinated against COVID-19?

We already know that current batches of vaccines trigger our immune system to produce cells that protect against severe forms of COVID-19. These include "killer cells," which recognize virus-infected cells and kill them, and so-called "memory cells," which store the memory of the virus and engage the immune system in action if the virus tries to infect a person again after vaccination.

These memory cells are supposed to stimulate an immune response that neutralizes the coronavirus before it can make you feel sick again. For these reasons, it is not yet clear whether revaccination will be needed in 1 year. Studies are currently underway to determine the degree of protection provided by the human body's immune system.

How long does immunity against COVID-19 last after vaccination? And how long after COVID-19?

To date, studies show that the immune response from the used vaccines remains strong for at least eight months. Of course, it's important to remember that COVID-19 vaccines began to be introduced largely only in December 2020, so data on their long-term effectiveness are still being collected, and it's likely that over time we'll see the effects last longer than is currently known.

What are the general and specific contraindications for vaccination?

Contraindications are specified in the summary of the product characteristics for each vaccine.

What is the relevance of vaccination of young people, children and athletes?

Young people and children in general carry mild forms of COVID-19. In some cases, unfortunately, they can have severe forms of the disease. However, in all cases, children remain active carriers and contribute to the spread of the disease. If they are vaccinated, they can be protected and protect those, who live in their community.

Which vaccine is better and produces more antibodies for a longer period?

All approved vaccines provide protection against serious forms of the disease and have a comparable safety profile. Any available vaccine is good.

Thus, antibody tests can help scientists and public health experts better understand the epidemiology of people and populations at higher risk of contracting COVID-19.

Although immune correlations of protection are not yet fully understood, the evidence indicates that the production of antibodies after infection likely gives some degree of immunity from subsequent infection for at least 6 months.

However, it is also unknown to what extent the new viral variants of concern may affect immunity to subsequent infection.

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