Possible SARS-CoV-2 Persistence:
FDA and CDC Should Further Expand Eligibility for Covid-19 Boosters*
by
Robert A. Michaels; PhD, CEP RAM TRAC Corporation; Schenectady, New York; USA
Abstract
In the Fall of 2021, the US FDA and CDC expanded eligibility for Pfizer Covid-19
booster shots but imposed inadvisable restrictions. Two issues support unrestricted booster eligibility: SARS-CoV-2 is strongly selected for exploiting personal immunological
weaknesses, resulting in weakened immune protection and slower immune response with
increasing viral adaptation. Further, the virus might be persistent, which means that it might remain dormant in immune-privileged 'refugia' such as the central nervous system
of previously infected people, even if their Covid-19 symptoms had been mild or nonexistent. Opportunistic re-activation of dormant viruses can cause severe illness, as in
childhood chickenpox producing adult shingles decades later. External re-infection is
unnecessary. Consistent with the 'precautionary principle', the overriding FDA and CDC public health priority should be to prevent as many SARS-CoV-2 infections as possible,
not tolerate them, assuming optimistically that they will not impose major public health and associated economic burdens in the future.
_______________________________ *CITATION: Michaels, Robert A. Possible SARS-CoV-2 persistence: FDA and CDC should further expand eligibility for Covid-19 boosters. ResearchGate, https://www.researchgate.net/publication/355175962_Possible_SARS-CoV2_Persistence_FDA_and_CDC_Should_Further_Expand_Eligibility_for_Covid19_Boosters, 11 October 2021.
RA Michaels, possibly persistent SARS-CoV-2
Introduction
The issue of whether the SARS-CoV-2 virus might persist after Covid-19 disease symptoms are gone remains unresolved, and largely unaddressed (for example, Alpalhão
et al. 2020). In the Fall of 2021, the US FDA (2021) and US CDC (2021) expanded eligibility to receive Pfizer Covid-19 booster shots. The agencies, however, imposed
eligibility restrictions that merit evaluation in the context of the hypothesis of SARS-CoV-
2 persistence, re-activation, and possible future disease burdens.
Methods
Assessment of the hypothesis of SARS-CoV-2 persistence, re-activation after
‘cure’, and possible future disease burdens is solely based upon literature research on evidence of SARS-CoV-2 invasion of privileged immune ‘refugia’ and resulting long-term
persistence. No laboratory or clinical activities were undertaken. No human research, and
therefore no associated ethical issues, were involved. No institutional review board approvals were required.
Findings
Two issues together suggest the need for unrestricted booster eligibility (and access). Variants, such as the current delta variant, are being selected strongly to exploit
personal immunological weaknesses (for example, Goldman 2021). Progressive viral
adaptation has produced increasing susceptibility to SARS-CoV-2 infection and increasingly frequent breakthrough infections (infections among fully vaccinated people;
Kustin et al. 2021, Scheepers et al. 2021). Booster vaccinations would counter these trends by enhancing levels of circulating antibodies, which otherwise wane naturally with time.
In conjunction with other immune system components, such as T cells and memory B cells, boosters therefore would accelerate immune response and thereby strengthen protection
against possible SARS-CoV-2 infection.
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RA Michaels, possibly persistent SARS-CoV-2
The biological plausibility of SARS-CoV-2 persistence after ‘cure’ is suggested by its ability to affect both the animal central nervous system (CNS; Dias de Melo et al. 2021)
as well as the human CNS (Meinhardt, et al. 2021). SARS-CoV-2 is a human respiratory virus and, like other human respiratory viruses, appears to be an opportunistic human CNS
pathogen (Desforges et al. 2019) that can cross the blood-brain barrier (Boldrini et al.
2021). Consistently, the virus is strongly associated with Covid-19 symptoms affecting memory, commonly including ‘brain fog’. The CNS is an immune-privileged refuge (Petri
2020), which could facilitate viral evasion of otherwise robust immune surveillance.
Discussion
Though uncertain, the hypothesis of SARS-CoV-2 persistence (Jacobs 2021) is more than speculation, as it is evidently biologically plausible. Many viruses are persistent
if they invade one or more of the body’s immune-privileged ‘refugia’, which are not limited
to the CNS. That is, in people who contract Covid-19, the issue of SARS-CoV-2 persistence might depend primarily on whether the virus entered an immune-privileged
location. It might depend only secondarily, if at all, on whether the infected person had experienced severe symptoms, or any symptoms.
Persistent viruses, shielded from effective immune surveillance, can re-emerge
opportunistically. This is especially likely to happen when people become weakened
physiologically by malnutrition or with other illnesses, or immunologically with aging. Re-emergence of persistent viruses does not depend upon new exposure or external
re-infection.
Re-activation of long-dormant viruses also can cause severe illness (Petri
2020). Examples include childhood chickenpox (Varicella zoster). The chickenpox may have been 'cured', but the virus may persist, and cause shingles many decades
later. Likewise, people ‘cured' of Ebola still may harbor the virus and may initiate Ebola outbreaks years later (Liverpool 2021).
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RA Michaels, possibly persistent SARS-CoV-2
Conclusion
More than speculation, the issue of possible SARS-CoV-2 persistence meets the
standard of a plausible, biologically credible hypothesis that might (I would say, does) merit further investigation. Its potential clinical importance also merits application of the
‘precautionary principle’ to prevent serious credible, even though uncertain, public health
consequences. FDA and CDC, perhaps more focused on the safety of the Pfizer vaccine than on the uncertain long-term danger of SARS-CoV-2 infections, did not do this. The
Agencies’ overriding public health concern should be to prevent as many future SARSCoV-2 infections as possible, which requires further expansion of eligibility for Covid-19
boosters. Covid-19 is not a disease that should be tolerated, even among people vaccinated against it, under the optimistic assumption that such infections will not impose major
public health and associated economic burdens in the future.
Literature Cited
Alpalhão, M.; J. A. Ferreira , and P. Filipe. Persistent SARS-CoV-2 infection and the risk for cancer. Medical Hypotheses, 143(109882),
https://doi.org/10.1016/j.mehy.2020.109882, online 28 May 2020;
Boldrini, M.; P. D. Canoll, and R. S. Klein. How Covid-19 affects the brain. JAMA
Psychiatry, 78(6):682-3, June 2021;
Desforges, M.; A. Le Coupanec, P. Dubeau, A. Bourgouin, L. Lajoie, M Dubé, P. J. Talbot. Human coronaviruses and other respiratory viruses: underestimated
opportunistic pathogens of the central nervous system? Viruses, 12(14), doi:
10.3390/v12010014, 20 December 2019;
Dias de Melo, G. D.; F. Lazarini, S. Levallois, C. Hautefort, V. Michel, F. Larrous, B. Verrilaud, C. Aparicio, S. Wagner, G. Gheusi, et al. COVID-19-related anosmia
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is associated with viral persistence and inflammation in human olfactory
epithelium and brain infection in hamsters. Science Translational Medicine, 10.1126/scitranslmed.abf8396, 3 May 2021;
Goldman, E. How the unvaccinated threaten the vaccinated: a Darwinian perspective.
PNAS 118(39), https://doi.org/10.1073/pnas.2114279118, 2021;
Jacobs, J. J. L. Persistent SARS-2 infections contribute to long Covid-19. Medical
Hypotheses, 149(110538), 4 pages; https://doi.org/10.1016/j.mehy.2021.110538, online 16 February 2021;
Kustin, T.; N. Harel, U. Finke, S. Perchik, S. Harari1, M. Talia, K. Kustin, N. Harel, U. Finkel, P. Shay, et al. Evidence for increased breakthrough rates of SARS-
CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals. medRxiv preprint, doi: https://doi.org/10.1101/2021.04.06.21254882; posted 9 April 2021;
Liverpool, L. Ebola may persist in the body for years before sparking new outbreaks. New Scientist, https://www.newscientist.com/article/2271847-ebola-may-persist-
in-the-body-for-years-before-sparking-new-outbreaks/, 18 March 2021;
Meinhardt,J.; J. Radke, C. Dittmayer, J. Franz, C. Thomas, R. Mothes, M. Laue, J.
Schneider, S. Brünink, S. Greuel, et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19.
Nature Neuroscience, 24:168-75, February 2021;
Petri, W. Does coronavirus linger in the body? What we know about how viruses in general hang on in the brain and testicles, https://theconversation.com/does-
coronavirus-linger-in-the-body-what-we-know-about-how-viruses-in-general-
hang-on-in-the-brain-and-testicles-142878, 31 July 2020;
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Scheepers, C.; J. Everatt, D. G. Amoako, A. Mnguni, A. Ismail, B. Mahlangu, C. K.
Wibmer, E. Wilkinson, H. Tegally, J. E. San, et al. The continuous evolution of SARS-CoV-2 in South Africa: a new lineage with rapid accumulation of mutations
of concern and global detection. medRxiv preprint doi: https://doi.org/10.1101/2021.08.20.21262342; posted 24 August 2021;
US CDC. CDC statement on ACIP [Advisory Committee on Immunization Practices] booster recommendations. U. S. Centers for Disease Control and Prevention,
https://www.cdc.gov/media/releases/2021/p0924-booster-recommendations-.html, 24 September 2021;
US FDA. FDA authorizes booster dose of Pfizer-BioNTech Covid-19 vaccine for certain populations. U. S. Food and Drug Administration, https://www.fda.gov/news-
events/press-announcements/fda-authorizes-booster-dose-pfizer-biontech-covid19-vaccine-certain-populations, 22 September 2021.
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Publication citation
Michaels, RA. Possible SARS-CoV-2 persistence: FDA and CDC should further expand eligibility for Covid-19 boosters. ResearchGate, https://www.researchgate.net/publication/355175962_Possible_SARS-CoV-2_Persistence_FDA_and_CDC_Should_Further_Expand_Eligibility_for_Covid-19_Boosters, 11 October 2021;