Breakthrough COVID-19 infections among the vaccinated may not be a severe threat

What are breakthrough COVID-19 infections: A breakthrough infection is a case of illness in which a vaccinated individual becomes sick from the same illness that the vaccine is meant to prevent. Previously, breakthrough infections have been identified in individuals immunized against a variety of different diseases including Mumps, Varicella (Chicken Pox), and Influenza and mostly these infections in the vaccinated individuals only result in mild symptoms and are normally of shorter duration [1].

CDC defines breakthrough COVID-19 infection as ‘A person who has SARS-CoV-2 RNA or antigen detected on a respiratory specimen collected ≥14 days after completing the primary series of a U.S. Food and Drug Administration (FDA)-authorized COVID-19 vaccine’ [2].

Are these breakthrough infections a major concern? Several studies have been conducted on breakthrough COVID-19 infections in various parts of the world and the following can be summarized from them [3-15]: 

• Breakthrough COVID-19 infections largely remain asymptomatic or mild and very rarely lead to hospitalization or death. Many vaccines have been found to be effective against the new variants inclusive of the lethal ones. Indian Council of Medical Research (ICMR) recently stated that in India, 2-4 per 10,000 got infected with COVID19 after vaccinations.
• It has been suggested that natural COVID-19 infections or vaccinations help in generating cell-mediated immunity which is minimally affected by the variant mutations and this plays a major role in the prevention of severe disease. Variant mutations have been found to have a negligible effect on the global CD4+ and CD8+ T cell responses and these T cell responses may contribute to limiting COVID-19 severity that could be caused by variants that have partially or largely escaped the neutralizing antibodies. Thus, the circulating memory T cells in vaccinated individuals and in those that have been previously infected would at least reduce COVID-19 severity if not prevent infection.
• High concentrations of SARS-CoV-2 IgG antibodies were detected in the oral and nasal mucosa specimens of vaccinated individuals as well as in the non-vaccinated individuals with previous SARS-CoV-2 infection and it was found that these antibodies persisted for a long period of time. The presence and persistence of such high antibody concentrations at sites of primary infection have been suggested to play a very significant role in the protection as well as prevention of viral transmission.
• It was found that an increase in vaccine coverage preceded the decline in mortality amongst the elderly population. This rapid increase in immunization coverage amongst the elderly was associated with a reduction in the proportionate mortality rate ratios for the elderly.
• Previously, viral load has been shown to be associated with COVID-19 symptomatic disease, and in vaccinated individuals, this viral load has been found to be decreased up to 2.8–4.5-fold. Thus, it has been suggested that COVID-19 vaccines might reduce the viral load in breakthrough infections and thereby further suppress onward transmission. 
• Various vaccine manufacturers are working on booster vaccine doses that would target the new variants of concern in order to overcome the partial resistance to neutralizing antibodies generated by natural infections or vaccinations.  

Conclusion: Owing to the above observations we can safely conclude that COVID-19 breakthrough infections, though inevitable, may not pose a severe threat in the future. As is stated by Dr. Anthony Fauci “It is inevitable that some people who have been fully vaccinated against the coronavirus will still get a "breakthrough" infection because no vaccine is 100 percent effective. However, even if a vaccine fails to protect against infection, it often protects against serious disease.” [16].

Let us look at the latest status of Israel on how the vaccines have performed so far.

Israel presents: How vaccines beat COVID-19 (for now)

Since mid-Jan peak:

99% fewer cases (now ~5 daily cases per million)
98% fewer critically ill (now ~0.4 daily per million)
98% fewer deaths (now ~0.2 daily per million)

Life is back to normal, very few restrictions remain pic.twitter.com/TlrwLW5xXa

— Eran Segal (@segal_eran) May 9, 2021

References: 

1. Wikipedia contributors. (2021, April 21). Breakthrough infection. In Wikipedia, The Free Encyclopedia. Retrieved 15:04, May 6, 2021, from https://en.wikipedia.org/w/index.php?title=Breakthrough_infection&oldid=1019166390.
2. COVID-19 Breakthrough Case Investigations and Reporting. https://www.cdc.gov/vaccines/covid-19/health-departments/breakthrough-cases.html. 
3. TYAGI K, GHOSH A, NAIR D, DUTTA K, Singh BHANDARI P, Ahmed ANSARI I, MISRA A, Breakthrough COVID19 Infections after Vaccinations in Healthcare and Other Workers in a Chronic Care Medical Facility in New Delhi, India, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, https://doi.org/10.1016/j.dsx.2021.05.001. 
4. ICMR: Covaxin found to be effective against Brazilian variant of virus too. Read more at:http://timesofindia.indiatimes.com/articleshow/82361064.cms?utm_source=contentofinterest&utm_medium=text&utm_campaign=cppst. 
5. Abu-Raddad LJ, Chemaitelly H, Butt AA; National Study Group for COVID-19 Vaccination. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants [published online ahead of print, 2021 May 5]. N Engl J Med. 2021;10.1056/NEJMc2104974. doi:10.1056/NEJMc2104974.
6. Shinde V, Bhikha S, Hoosain Z, et al. Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant [published online ahead of print, 2021 May 5]. N Engl J Med. 2021;10.1056/NEJMoa2103055. doi:10.1056/NEJMoa2103055.
7. Teran RA, Walblay KA, Shane EL, et al. Postvaccination SARS-CoV-2 Infections Among Skilled Nursing Facility Residents and Staff Members — Chicago, Illinois, December 2020–March 2021. MMWR Morb Mortal Wkly Rep 2021;70:632-638. DOI: http://dx.doi.org/10.15585/mmwr.mm7017e1. 
8. Keehner J, Horton LE, Pfeffer MA, et al. SARS-CoV-2 Infection after Vaccination in Health Care Workers in California. N Engl J Med. 2021;384(18):1774-1775. doi:10.1056/NEJMc2101927.
9. Tarke A, Sidney J, Methot N, et al. Negligible impact of SARS-CoV-2 variants on CD4 + and CD8 + T cell reactivity in COVID-19 exposed donors and vaccinees. Preprint. bioRxiv. 2021;2021.02.27.433180. Published 2021 Mar 1. doi:10.1101/2021.02.27.433180.
10. Redd AD, Nardin A, Kared H, et al. CD8+ T cell responses in COVID-19 convalescent individuals target conserved epitopes from multiple prominent SARS-CoV-2 circulating variants. Preprint. medRxiv. 2021;2021.02.11.21251585. Published 2021 Feb 12. doi:10.1101/2021.02.11.21251585.
11. Detection of persistent SARS-CoV-2 IgG antibodies in oral mucosal fluid and upper respiratory tract specimens following COVID-19 mRNA vaccination. Aubree Mades, Prithivi Chellamuthu, Lauren Lopez, Noah Kojima, Melanie A MacMullan, Nicholas Denny, Aaron N Angel, Joseph Casian, Matthew Brobeck, Nina Nirema, Jeffrey D Klausner, Frederick E Turner, Vladimir I Slepnev, Albina Ibrayeva medRxiv 2021.05.06.21256403; doi: https://doi.org/10.1101/2021.05.06.21256403. 
12. Estimating the early impact of immunization against COVID-19 on deaths among elderly people in Brazil: analyses of secondary data on vaccine coverage and mortality. Cesar Victora, Marcia C Castro, Susie Gurzenda, Aluisio J D Barros medRxiv 2021.04.27.21256187; doi: https://doi.org/10.1101/2021.04.27.21256187.
13. Levine-Tiefenbrun, M., Yelin, I., Katz, R. et al. Initial report of decreased SARS-CoV-2 viral load after inoculation with the BNT162b2 vaccine. Nat Med (2021). https://doi.org/10.1038/s41591-021-01316-7.
14. Hacisuleyman E, Hale C, Saito Y, et al. Vaccine Breakthrough Infections with SARS-CoV-2 Variants [published online ahead of print, 2021 Apr 21]. N Engl J Med. 2021;10.1056/NEJMoa2105000. doi:10.1056/NEJMoa2105000.
15. A DC, F C, N P, et al. SARS-CoV-2 escape mutants and protective immunity from natural infections or immunizations [published online ahead of print, 2021 Mar 29]. Clin Microbiol Infect. 2021;S1198-743X(21)00146-4. doi:10.1016/j.cmi.2021.03.011.
16. Fauci: Breakthrough infections after vaccinations 'inevitable'. https://news.yahoo.com/fauci-breakthrough-infections-vaccinations-inevitable-173725342.html.

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