The Strange Case of BCG and COVID-19: The Verdict Is Still up in the Air

Abstract

COVID-19, caused by a novel coronavirus, SARS-CoV-2, contributes significantly to the morbidity and mortality in humans worldwide. In the absence of specific vaccines or therapeutics available, COVID-19 cases are managed empirically with the passive immunity approach and repurposing of drugs used for other conditions. Recently, a concept that bacilli Calmette–Guerin (BCG) vaccination could confer protection against COVID-19 has emerged. The foundation for this widespread attention came from several recent articles, including the one by Miller et al. submitted to MedRxiv, a pre-print server. The authors of this article suggest that a correlation exists between countries with a prolonged national BCG vaccination program and the morbidity/mortality due to COVID-19. Further, clinical BCG vaccination trials are currently ongoing in the Netherlands, Australia, the UK, and Germany with the hope of reducing mortality due to COVID-19. Although BCG vaccination helps protect children against tuberculosis, experimental studies have shown that BCG can also elicit a non-specific immune response against viral and non-mycobacterial infections. Here, we summarize the pros and cons of BCG vaccination and critically analyze the evidence provided for the protective effect of BCG against COVID-19 and highlight the confounding factors in these studies.

Pneumococcal and Influenza Vaccination Rates and Pneumococcal Invasive Disease Rates Set Geographical and Ethnic Population Susceptibility to Serious COVID-19 Cases and Deaths

“…The results reported here add to the literature reviewed in the Introduction that cast doubt on studies reporting that BCG, polio, or DPT vaccinations may protect against COVID-19 acquisition or death [64][65][66][67][68][69][70][71][72][73][74][75][76]. However, one important caveat must be mentioned, which is that it was not possible in this study to differentiate between nations using acellular pertussis vaccines, those using whole-cell pertussis vaccines, and those using both as part of their vaccination programs.…”

On BCG Vaccine Protection from COVID-19: A Review

“…Similar to the former group, epidemiological data were collected from institutional databases due to the data availability. Although these data can indicate a beneficial effect of BCG vaccinations, such researches may not provide definitive evidence of causal relationship [ 59 ]. (c) Observational studies where relationships between two subgroups were observed.…”

Current State of the First COVID-19 Vaccines

“…Based on 100 years of using BCG as a vaccine, BCG is considered safe. The principal of using BCG against COVID-19 has been proposed because of its effectiveness against tuberculosis [ 68 ] and questioned because of the non-specificity of the immune response [ 69 ]. First evidence that BCG might be effective against COVID-19 was obtained from a retroactive cohort study.…”