At the beginning of the COVID-19 pandemic, antibodies to SARS-CoV-2 antibodies determined if any people had been infected with the virus, and many scientists believed that the presence of antibodies would help ease the severe lockdown. The original idea was that those with antibodies would be immune and would not be re-infected, at least temporarily, so they could move freely without endangering themselves or others. As the pandemic progressed, the idea of ​​an “immunity passport” based on the presence of antibodies unfortunately did not seem to provide the solution. The questions that associated antibodies with protection against infection remained unanswered, as for example it is not entirely clear which specific antibodies protect against re-infection with SARS-CoV-2, how high their levels should be, and for how long provide adequate protection against COVID-19.
Vaccine approval for COVID-19 brought antibody tests back to the forefront. This time, the idea was that with a simple blood test for antibodies, the vaccinated could check if the vaccine “worked” and, later, if they should take a booster dose. A recent article in the journal JAMA presents potential problems and errors in assessing immunity to SARS-CoV-2 based on antibody tests. The Professors of EKPA Ourania Tsitsiloni, Evangelos Terpos, Ioannis Trougakos and Thanos Dimopoulos (Rector of EKPA) summarize the main points of the article.
Antibody tests against SARS-CoV-2, which were eventually licensed for emergency use (EUA) by the US FDA, cannot predict antiviral protection based on the levels of antibodies measured. In particular, in May 2021, the FDA issued repeated announcements highlighting the following:
1. Some tests detect antibodies produced by the immune system only after a natural infection with the virus and therefore, people who were not infected could be negative for these antibodies, despite the fact that they have acquired immunity after vaccination. Therefore, the results of these antibody tests should not be used to assess a person’s level of immunity or protection from COVID-19, especially after vaccination.
2. The antibody test was not designed to assess immunity and protective antibodies, as their protective levels have not yet been determined. What we do know is that antibodies that recognize the SARS-CoV-2 spike protein (S) (especially neutralizers) are associated with protection. However, there is no clear level (“title”) that ensures full protection. In Israel, for example, of the approximately 1,500 vaccinated health workers with the BNT162b2 (Pfizer-BioNTech) vaccine, 39 who became infected (having received the second dose of the vaccine) had lower levels of neutralizing antibodies than those who did not. Therefore, high levels of neutralizing antibodies are an important parameter, but how “sufficiently high” is determined is unknown.
3. Laboratory antibody tests have not yet been standardized. Some tests simply give a positive or negative result, with no antibody values. Quantitative ones use different methods, detect different classes of antibodies and determine values ​​with different units of measurement. In order to set protection limits, the tests must be standardized and calibrated, as has been done with antibody tests for other vaccine-preventable diseases, such as tetanus, diphtheria and measles. Currently, only one SARS-CoV-2 calibrated antibody test according to the WHO reference standard is commercially available, that of Ortho-Clinical Diagnostics.
4. Measurement of neutralizing antibodies requires complex live or inactivated virus tests performed in only a few laboratories and are currently not available for widespread diagnostic use. Especially for some tests available “for home use” (such as Epitome Risk Solutions’ cPass), the company itself states that positive results should not be interpreted as an indication of adequate immunity or protection against possible re-infection.
Circulating antibodies do not give the full picture of immunity to SARS-CoV-2. They peak 2-3 months after natural infection or vaccination, but then begin to decline. The immune component associated with protection is the B and T cells of memory, which “remember” to have seen the SARS-CoV-2 spike protein before. Studies to date have shown that memory cells remain for at least 6-8 months and are activated, protecting the body from severe COVID-19 in the event of re-infection.
6. Finally, it appears that as antibodies decrease over time, susceptibility to asymptomatic or mild COVID-19 infections increases. It is therefore recommended that the booster dose be given to people at higher risk of serious illness, such as adults over the age of 65, adults with certain underlying illnesses, people living or working in high-risk areas, or living in long-term care facilities, and still, individuals who are moderately to severely immunosuppressed and have already been vaccinated with the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines. According to the US Centers for Disease Control (CDC), the presence of high levels of neutralizing antibodies in the blood does not prevent the virus from attaching to the upper respiratory tract and starting to multiply, but the infection is likely to be asymptomatic.
Therefore, in order to avoid infection by SARS-CoV-2, the known combination of measures: vaccination, frequent hand washing, use of a mask and avoid crowding a large number of people indoors, especially in areas with high cases.
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