Protection against SARS-CoV-2 by BCG vaccination is not supported by epidemiological analyses

Abstract

The Bacillus Calmette–Guerin (BCG) vaccine provides protection against tuberculosis (TB), and is thought to provide protection against non-TB infectious diseases. BCG vaccination has recently been proposed as a strategy to prevent infection with SARS-CoV-2 (CoV-2) to combat the COVID-19 outbreak, supported by its potential to boost innate immunity and initial epidemiological analyses which observed reduced severity of COVID-19 in countries with universal BCG vaccination policies. Seventeen clinical trials are currently registered to inform on the benefits of BCG vaccinations upon exposure to CoV-2. Numerous epidemiological analyses showed a correlation between incidence of COVID-19 and BCG vaccination policies. These studies were not systematically corrected for confounding variables. We observed that after correction for confounding variables, most notably testing rates, there was no association between BCG vaccination policy and COVD-19 spread rate or percent mortality. Moreover, we found variables describing co-morbidities, including cardiovascular death rate and smoking prevalence, were significantly associated COVID-19 spread rate and percent mortality, respectively. While reporting biases may confound our observations, our epidemiological findings do not provide evidence to correlate overall BCG vaccination policy with the spread of CoV-2 and its associated mortality.

The association of Coronavirus Disease-19 mortality and prior bacille Calmette-Guerin vaccination: a robust ecological analysis using unsupervised machine learning

“…Neither the implementation of rapid contract tracing with targeted isolation, widespread testing, nor regional lockdowns had been as readily deployed in many countries upon the analysis CRM in the present work 26 , 27 . Hensel et al found that for countries with high testing rates, BCG vaccination no longer correlated with incidence 28 . However, in countries with current BCG vaccination policies and higher rates of testing, BCG vaccination remained significantly associated with reduced rates of CRM 28 .…”

“…Hensel et al found that for countries with high testing rates, BCG vaccination no longer correlated with incidence 28 . However, in countries with current BCG vaccination policies and higher rates of testing, BCG vaccination remained significantly associated with reduced rates of CRM 28 . For Israeli adults aged 35–41 with symptoms suggestive of COVID-19, no difference was found in incidence for those born during BCG vaccination programs or those born just after they ended.…”

Therapies Targeting Trained Immune Cells in Inflammatory and Autoimmune Diseases

“…In this context, trained immunity induced by BCG vaccination protects from several viral infections ( 71 , 72 ). However, attempts to find an association between BCG vaccination status and COVID-19 severity have yielded inconclusive results ( 73 , 74 ).…”

Silence of the Lambs: The Immunological and Molecular Mechanisms of COVID-19 in Children in Comparison with Adults

“…However, analysis of the available data has clearly highlighted that no definitive conclusions in this regard can be drawn, as the studies were not systematically corrected for confounding variables, such as cardiovascular death rates and smoking prevalence. When confounding variables were considered, no correlation between overall BCG vaccination policy and spread of SARS-CoV-2 and its associated mortality was found [ 62 ]. Further studies are ongoing.…”