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The SARS-CoV-2 Virus And Our Immune Response

Posted on Nov 17, 2020
Norbert Gleicher, MD

In this article, CHR’s Medical Director and Chief Scientist, Norbert Gleicher, MD, shares his personal experience with COVID-19. His encounter with the virus adds to the growing body of evidence that points to the existence of non-specific immunity that protects against a range of similar viruses. Here it is, in his own words.

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Here is for once a somewhat happy COVID-19 pandemic story. At already somewhat advanced age, I am still an actively practicing physician-scientist in New York City, since April regularly tested by nasal swab and PCR for the SARS CoV-2 virus and, intermittently for antibodies. I also practice mitigation through social distancing, maintain appropriate hand hygiene and wear surgical masks at work as well as in public.

First tested for IgM/IgG antibodies on April 23, I was negative. At the same time (using the same test), my 24-year old daughter (and a friend) tested positive. She retrospectively, remembered in March, during what she then had perceived as a routine cold, to have lost taste and smell for a few days. This was when first reports surfaced linking ageusia (loss of taste) and anosmia (loss of smell) to COVID-19.1

On July 22, I had to fly to Vienna, Austria. I was retested for the virus on July 17 and 18 since entry required a negative test within 5 days. Both tests at different PCR laboratories were negative. On July 28, one day before my return to the U.S., I underwent another negative viral swab and PCR test at a university laboratory in Vienna. Back in New York City, another test on August 8 was again negative (see Table).

Table  Testing Schedule

Completely asymptomatic, I did not retest till October 5 for virus (swab) and antibodies (blood). My viral test was again negative; but my antibody test, suddenly, had turned positive, suggesting I had developed immunity against the SARS-CoV-2 virus. I immediately repeated the test, confirming the result.
Sometime between April 23 and October 5, my immune system, therefore, must have made contact with the SARS-CoV-2 virus and, in response, started production of antibodies. Since IgG antibodies take at least 7 to 10 days from exposure,2 the event must have occurred before October 5. Yet, not even once during this time period, did I experience even the most minimal symptoms.

This is what makes this short report relevant, because it demonstrates the unpredictability of the SARS-CoV-2 virus and our still limited understanding of how the immune system may respond. Only two explanations appear possible: My first antibody test on April 23 could have been a false-negative, which would mean that I had lived through the worst pandemic in NYC in 100 years without knowing that I was already immune. The manufacturer of the negative antibody test in April, however, claimed sensitivity of 92.6% and specificity of 96.7% (per package insert, SD BIOSENSOR, Republic of Korea). Moreover, the same test apparently correctly diagnosed my daughter (and a friend) as antibody positive. A false-negative diagnosis, therefore, appears unlikely.

Sometime between the end of April and mid-September, my immune system must, therefore, have been challenged by the virus to produce antibodies; yet, somehow, this happened without even a single symptomatic sniffle, even though I am clearly, simply because of age, a high-risk candidate for severe disease. My immune system, therefore, must have been unexpectedly efficient in holding the virus abreast.

Only a few months ago, the story would have ended here, and I would have been grateful for a small “miracle.” But nobody knew then that, in addition to our adaptive immune response through highly specific immobilizing antibodies, we also have innate long-term cellular anti-viral immunity.2,3 In contrast to virus-specific antibody responses, the cellular response is cross-reactive, allowing viruses to produce immune-memory toward other, similar viruses. Even without ever having been exposed to viruses, earlier immune responses to other viruses may, therefore, have produced adequate innate cellular immunity against a, previously to my immune system, unknown virus. This cross-reactive anti-viral immunity, apparently, can successfully disarm even previously unknown viruses or, at least, facilitate only milder disease.

Two just published commentaries well summarized these new discoveries,2,3 reported in only a handful of papers from Europe and the U.S. We, likely, still would not be aware of innate anti-viral immunity, had the COVID-19 pandemic not occurred and created convincing evidence for such cross-reactive long-term immunity against the SARS-CoV-2 virus. Virologists, therefore, proposed that activating the innate immune system in a non-specific defense against the SARS-CoV-2 virus could be achieved by immunizing the population with Salk’s oral polio vaccine until more specific COVID-19 vaccines become available.4

I surely had enough colds and flu episodes in recent years to build up such long-term cross-reactive antiviral immunity to the SARS-CoV-2 virus and, in addition, received annual influenza vaccines for at least a decade. But there may have been another stroke of luck in having grown up in Europe, where children in those years were immunized with Bacillus Calmette-Guerin (BCG) against tuberculosis, recently also suggested to induce non-specific anti-SARS-CoV-2 immunity.5

In the end, we will never know where my antibody immunity to the SARS-CoV-2 virus suddenly came from. Long-term innate anti-viral immunity, likely, saved me from getting sick when the virus, despite all mitigation, still broke through my physical defenses. In response, my immune system, likely, mounted in addition to the innate immune response an adaptive antibody response, further augmenting the former. Today, though, I cannot even guess when all of this happened.

Within this context, we were pleased to witness how “protected” from the virus New York City has become after a very severe first wave of infections that ended in early May, likely, reflecting much more substantial immunity in the population than reported in published anti-SARS-CoV-2 antibody rates.6 We since then also learned that anti-viral innate cellular immunity can significantly lower required antibody-mediated immunity in communities to reach herd immunity, from as much as 60% to only approximately 20 percent.3 My experience with the virus may, thus, not have been such a miracle after all. Experiences like mine may, indeed, be exactly the reason why New York City and the whole Northeast of the country have so-far remained relatively unaffected by the still ongoing second and third waves of infections.

Conflict statement: The author reports no conflict.
Editorial statement: Dr. Gleicher also recently published a paper in the medical journal Reproductive Biology and Endocrinology that summarizes CHR’s experience during the pandemic. As one of only very few fertility centers in NYC and the country as a whole, CHR did not shut down during the heydays of the pandemic, as the first wave between March and May hit the city very badly. This story, therefore, makes good reading for patients as well as colleagues. The manuscript can be accessed for free at https://doi.org/10.1186/s12958-020-00663-3.

References
  1. Makaronidis J, Mok J Balogun N, Magee CG, Omar RZ, Carnemolla A, Batterham RL. Seroprevalence of SARS-CoV-2 antibodies in people with an acute loss in their sense of smell and/or taste in a community-based population in London, UK: An observational cohort study. PLoS Med 2020; 17(10):e1003358. https://doi.org/10.1371/journal.pmed.1003358
  2. Stephens DS, McElrath MJ. COVID-19 and the path to immunity. JAMA 2020; 324(13(:1279-1281
  3. Doshi P. Covid-19: Do many people have pre-existing immunity? BMJ 2020;370:m3563; doi: 10.1136/bmj.m3563
  4. Gallo R. The case for a stopgap vaccine. The New York Times. https://www.nytimes.com/2020/06/25/opinion/letters/coronavirus-vaccine-gallo.html, June 25, 2020
  5. Madan M, Pahuja S, Mohan A, Pandey RM, Madan K, Hadda V, Tiwari P, Guleria R, Mittal S. TB infections and BCG vaccination: Are we protected from COVID-19? Public Health 2020;185:91-92
  6. Gleicher N. The COVID-19 pandemic through eyes of a NYC fertility center: A unique learning experience with often unexpected results. Reprod Biol Endocrinol; 2020; In press;
Norbert Gleicher, MD, FACOG, FACS

Norbert Gleicher, MD, FACOG, FACS

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.

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