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COVID-19 antibody testing, revisited

COVID-19 antibody testing, revisited

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I wanted to thank Dr. Brad Feliz for his informative discussion of antibodies in his Register article ("The current state of COVID-19 antibody testing," May 30). In my opinion, his discussion of antibody testing and statements regarding its utility and purpose of use may lead the reader to the conclusion that, at least in Napa, it has no place in the assessment of one’s COVID-19 status. I believe this is incorrect.

Dr. Feliz cites 3 issues with antibody testing: 1) not all people produce antibodies (seroconvert) when they initially encounter the virus; 2) production of antibodies does not guarantee immunity, and antibody-positive people may spread the virus; 3) the prevalence of people with the virus is so low in Napa that the test is likely to lead to more false positive tests, indicating a response not to COVID-19, but to more common members of the coronavirus family such as the common cold.

Dr. Feliz is absolutely correct when he states that upon initial encounter with this virus, (or any pathogen), that people do not produce antibodies. As he discusses, antibody production starts with IgM (Immunoglobulin-M) antibodies 3-6 days after exposure. Upon exposure to any pathogen, the innate immune system initially responds (refer to my April 17 Letter to the Editor). Depending upon degree of exposure and the competency of one’s immune system, the innate immune system may deal with the threat before a significant antibody response (which is part of the adaptive or acquired immune system) occurs. In this respect, little or no antibody response is needed. This happens all the time, as we are constantly exposed to pathogens that we are never aware of. The vast majority of people will seroconvert when necessary, possibly with the exception of those who are severely immunologically compromised. Data from Vibrant America Labs (an FDA-EUA approved lab for COVID-19 antibody testing) showed that 100% of COVID-19-infected individuals seroconverted within a median time of 7 days.

With respect antibody testing cross-reacting with other coronavirus family members, this is incorrect, at least for FDA - Emergency Use Authorization approved labs. Part of the approval process includes tests for cross-reactivity to other viruses, including those mentioned by Dr. Feliz. no cross-reactivity was detected to any other virus.

If innate immunity does not resolve the problem, the adaptive immune system kicks in, producing antibodies, starting with IgM, and later IgG antibodies, which are long lived. This forms the basis of immunity to an entire array of infectious agents, and forms the rationale for vaccination or “immunization.” Exposure to an infectious agent, or an attenuated one, confers long-lived immunity. Prime examples of this are the polio and smallpox virus. Some viruses, such as cold and flu, evade this mechanism by constantly mutating. It has been recently shown however that antibodies from earlier exposure increase response to new flu strains.

Dr. Feliz is correct when he states that the presence of antibodies does not guarantee immunity. Since this is a new virus, no one knows if immunity is conferred with infection. The salient point here is that the intent of the antibody test is not to determine immunity, but to detect your response to the virus. In other words the circumstances under which the test is useful is to see if you have mounted an adaptive immune response to the virus. This tells you that you have been exposed to the virus. Ascribing various characteristics to the test that it isn’t designed to do, then saying it can’t do them is inappropriate. It can’t tell you if you have recovered or still have it. (Repeat testing in several weeks can be helpful in this regard. though).

Further, it can’t tell if you can spread the virus, so ascribing this characteristic to the test is improper also. The test also can’t tell if the oil in your car needs changing (a bad analogy for sure).

Dr. Feliz states that antibody testing can be inferior to RNA-PCR testing, considered the gold standard. He goes into some detail regarding specificity and sensitivity of antibody testing but does not do the same for RNA testing, stating that antibody testing suffers from false positives. He fails to state that RNA testing suffers from a huge percentage of false negatives, ranging from 2%-40%.

The bottom line is that both tests have their uses, depending upon circumstances. Antibody testing may be more useful for initial screening, due to low false negatives, while follow up RNA testing with its higher sensitivity may then confirm positives and help determine whether a patient has an active infection. Perhaps a more balanced article explaining the benefits and uses of each test would have been more helpful. References are available upon request.

Douglas L. Weed

Napa

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