BCG vaccine protection from severe coronavirus disease 2019 (COVID-19)

Abstract

<jats:p>A series of epidemiological explorations has suggested a negative association between national bacillus Calmette–Guérin (BCG) vaccination policy and the prevalence and mortality of coronavirus disease 2019 (COVID-19). However, these comparisons are difficult to validate due to broad differences between countries such as socioeconomic status, demographic structure, rural vs. urban settings, time of arrival of the pandemic, number of diagnostic tests and criteria for testing, and national control strategies to limit the spread of COVID-19. We review evidence for a potential biological basis of BCG cross-protection from severe COVID-19, and refine the epidemiological analysis to mitigate effects of potentially confounding factors (e.g., stage of the COVID-19 epidemic, development, rurality, population density, and age structure). A strong correlation between the BCG index, an estimation of the degree of universal BCG vaccination deployment in a country, and COVID-19 mortality in different socially similar European countries was observed (<jats:italic>r</jats:italic><jats:sup>2</jats:sup> = 0.88; <jats:italic>P</jats:italic> = 8 × 10<jats:sup>−7</jats:sup>), indicating that every 10% increase in the BCG index was associated with a 10.4% reduction in COVID-19 mortality. Results fail to confirm the null hypothesis of no association between BCG vaccination and COVID-19 mortality, and suggest that BCG could have a protective effect. Nevertheless, the analyses are restricted to coarse-scale signals and should be considered with caution. BCG vaccination clinical trials are required to corroborate the patterns detected here, and to establish causality between BCG vaccination and protection from severe COVID-19. Public health implications of a plausible BCG cross-protection from severe COVID-19 are discussed.</jats:p>

Exposure to Mycobacteria influences disease progression in COVID-19 patients&nbsp;

“…It has merit theoretically but is di cult to be established due to BCG vaccine's long preparatory period and known poor e cacy in adult population. 12 The present work probably establishes a direct correlation between Mtb induced Th1 immunity and protection against Covid-19. The restoration of Th1/Th2 imbalance may be a more natural strategy to ght against Covid-19.…”

“…Similar observations were made authors who reported strong correlation between the BCG index, an estimation of the degree of universal BCG vaccination deployment in a country, and COVID-19 mortality in different socially similar European countries (r2 = 0.88; P = 8 × 10−7). 12 COVID-19−related deaths are signi cantly higher in countries with higher quality of life, contradicting the expectation of lower rates of mortality in countries with improved health care systems. 12 Though India has become the third highest country with maximum number of Covid-19 patients, it continues to shows signi cantly lower prevalence of the disease, both in terms of disease and deaths per million population in comparison to other top 15-20 countries .22 Natural course for most of Covid-19 patients in Th1 predominant population may be to remain asymptomatic or minimally symptomatic which is re ected in the epidemiological reports from India and other similar countries like south America etc.…”

“…12 Though India has become the third highest country with maximum number of Covid-19 patients, it continues to shows signi cantly lower prevalence of the disease, both in terms of disease and deaths per million population in comparison to other top 15-20 countries .22 Natural course for most of Covid-19 patients in Th1 predominant population may be to remain asymptomatic or minimally symptomatic which is re ected in the epidemiological reports from India and other similar countries like south America etc. 12 Patients with moderate to severe symptoms from such a population, probably have pre-existing low immunity due to malnutrition or an associated co-morbidity. An unforeseen Th2 predominance due to worm infestation, subtle autoimmune or allergic disorder etc.…”

“…Human population living in a clean and hygienic environment grossly lack in Th1 immunity and overexpresses Th2 immunity due to the cross regulation between Th1 and Th2 immunity 11 and has shown a higher prevalence of Covid-19. [12][13][14] Could frequent exposure to strong Th1 antigens like Mycobacteria, malaria or Salmonella that is prevalent in the Indian population be the cause for lesser severity and lower mortality due to Covid-19, was the research question which we aimed to answer through the present study. We, therefore, performed measurements of Salmonella antibodies titre and Patient with Co morbid condition like malignancy, chronic renal failure, cardiomyopathy, Chronic respiratory failure with pre-existing dyspnoea, in ammatory diseases like rheumatoid arthritis, in ammatory bowel disease or patients on long term immuno-suppressants were excluded from the study.…”

“Proliferation of DBLOX Peroxidase-Expressing Oenocytes Maintains Innate Immune Memory in Primed Mosquitoes”

“…There is strong epidemiological evidence that BCG vaccination in infants has a broad protective effect and reduces the overall mortality from respiratory infections not related to tuberculosis (21)(22)(23), and there are ongoing clinical studies to establish if the BCG vaccine also protects from severe COVID19 (24,25). Furthermore, there is growing epidemiological evidence of reduced COVID19 mortality (26) and improved outcomes (27) in countries with strong BCG vaccination programs. However, little is known about the mechanism to establish and maintain trained immunity.…”