Antibodies

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Early in the COVID-19 pandemic, developers designed SARS-CoV-2 antibody tests to detect whether people had been infected. Some experts hoped that these tests would help ease lockdowns, as those with antibodies likely would be, temporarily at least, immune to reinfection therefore allowing them to reenter society without putting themselves and others at risk. But as the pandemic unfolded, the idea of an immunity passport didn’t pan out.

The reliability of early tests was questionable, plus it wasn’t known which antibodies protected against which variant and how high the antibody levels needed to be to assure immunity. So as time wore on, the public’s clamor for antibody testing waned, at least until the advent of the vaccines. Then the question became could a blood test evaluate the effectiveness of a vaccine and the length of time the vaccine provides a reliable defense.

The U.S. Food and Drug Administration (FDA) discouraged antibody testing as a do-it-yourself immunity check, and last September an FDA spokesman for the agency reiterated that position in an email published in the Journal of the American Medical Association. Many ignored that advice.

An article published in a November edition of the New York Times described concierge clinicians who were regularly testing their clients for COVID-19 antibodies, and based on these tests, advising the clients when they should get a booster vaccine. The problem isn’t just that the tests weren’t designed to assess immunity, it’s also that the protective antibodies and their thresholds haven’t been fully worked out yet. The issue is rather complex. For starters, not all antibodies are “neutralizing” antibodies. Neutralizing antibodies correlate with immunity whereas non-neutralizing ones bind to the virus but do not impart protection. Plus, antibodies obtained through viral illness differ from those obtained by vaccination. Also, as we have seen, both vaccination and prior illness do not provide complete protection from reinfection, although the severity of illness in those who are vaccinated or had a prior infection is mild in most cases.

Meanwhile, antibody tests have yet to be standardized. As of late last November, only one commercially available SARS-CoV-2 antibody tests made by Ortho-Clinical Diagnostics had been calibrated to the World Health Organization standard. Yet, as noted above, all antibodies bind to the virus but not all neutralize it and, so far, differentiating between those two types of antibodies is not possible. Even if the test could differentiate between those two types of antibodies, antibodies are only a part of the body’s overall immune response. White blood cells, specifically memory T cells and memory B cells, which last at least six to eight months in the bloodstream, are responsible for a significant portion of immunity. Reinfection causes these memory cells to morph into antibody-secreting cells, a process that can take three to five days. This may explain why reinfection among those with immunity usually results in a mild, shortened illness.

How often booster shots will be necessary remains to be seen. As one expert put it, repeatedly giving booster shots is like “rolling a stone up a hill, only to have it roll back down.” Ultimately, medical advice will probably continue to be vaccination and avoidance of and masking in crowded indoor settings, especially in high case-rate areas.

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By Peter Galvin, MG

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