“Trained immunity” from Mycobacterium spp. exposure or BCG vaccination and COVID-19 outcomes
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Abstract
Protective variables for Coronavirus Disease 2019 (COVID-19) are unknown."Trained immunity" of the populace as a result of Bacille Calmette-Gue ´rin (BCG) vaccination policy implementation and coverage had been suggested to be one of the factors responsible for the differential impact of COVID-19 on different countries.Several trials are underway to evaluate the potential protective role of BCG vaccination in COVID-19.However, the lack of clarity on the use of appropriate controls concerning the measures of "trained immunity" or the heterologous cell-mediated immunity conferred by BCG vaccination has been a cause of concern leading to more confusion as exemplified by a recently concluded trial in Israel that failed to find any protective correlation with regard to BCG vaccination.Whereas, when we analyze the COVID-19 epidemiological data of European countries without any regard for BCG vaccination policy but with similar age distribution, comparable confounding variables, and the stage of the pandemic, the prevalence of tuberculin immunoreactivity-a measure of cell-mediated immunity persistence as a result of Mycobacterium spp.(including BCG vaccine) exposure of the populations-is found consistently negatively correlated with COVID-19 infections and mortality.We seek to draw attention toward the inclusion of controls for underlying "trained immunity" and heterologous cell-mediated immunity prevalence that may be preexisting or resulting from the intervention (e.g., BCG vaccine) in such trials to arrive at more dependable conclusions concerning potential benefit from them. CommentaryBacille Calmette-Gue ´rin or BCG vaccination policy implementation by countries and its coverage had been proposed to lower the COVID-19 cases and mortality [1][2][3][4].The BCG vaccination given to children and adults has been known to protect them from many unrelated pathogens and diseases [1,3,5-10] supposedly through the generation of "trained immunity" and heterologous cell-mediated immunity (e.g., T helper 1 (Th1) and Th17) that last for a variable period [1,5,[9][10][11][12].However, the confounding variables among the countries for COVID-19 such as the stage of the outbreak, population age distribution, health infrastructure,
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Positive tuberculin sensitivity test prevalence inversely correlates with COVID-19 incidence in first-wave epidemiological observations.
“the prevalence of individuals with positive tuberculin sensitivity tests—either due to exposure to Mycobacterium spp. or BCG vaccination—inversely correlates with the incidence of COVID-19”
From COVID-19 and the human innate immune system (2021) · cites this paper as Singh et al., 2020
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COVID-19 and the human innate immune system
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- Authors
- Singh, S., Maurya, R. P., & Singh, R. K.
- Affiliations
- Institute of Medical Sciences (IN)
- Banaras Hindu University (IN)
- Corresponding author
- Singh, Samer
- Venue
- PLOS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2020-10-29
- Volume
- 16
- Issue
- 10
- Pages
- e1008969
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC7595322
- OpenAlex
- W3095439057
- Cited by
- 41
- References
- 24
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 9 · 2022: 13 · 2021: 14 · 2020: 3
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Department of Biotechnology, Ministry of Science and Technology, India
- Banaras Hindu University
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- trained immunity, BCG vaccination, COVID-19 pandemic, cell-mediated immunity, heterologous immunity, COVID-19 mortality, cross-protective immunity
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, BCG Vaccine, Humans, Immunity, Cellular, Mycobacterium, Pneumonia, Viral, Vaccination, Coronavirus Infections, Pandemics
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