key: cord-0807439-7pspbh64
authors: Weng, Chien-Hsiang; Chan, Philip A
title: BCG as an adjunct or alternative vaccine to prevent COVID-19?
date: 2020-09-19
journal: J Travel Med
DOI: 10.1093/jtm/taaa175
sha: 1c6a353cd3b239ecf9e569edf3e1b05625bb721a
doc_id: 807439
cord_uid: 7pspbh64

nan

recent study also showed that the BCG vaccination may induce a specific immunity against SARS-CoV-2 that targets the viral envelope protein that is essential for infectivity. 4 Several ecological studies found lower numbers of SARS-CoV-2 infections and reduced COVID-19 deaths in BCG-vaccinated regions, while our recent cohort study found lower hospitalization rates among BCG-vaccinated COVID-19 patients in the same communities in the Northeast Unites States even decades after vaccination. [5] [6] [7] These findings may indicate the potential of BCG vaccine in reducing the likelihood of severe COVID-19, and perhaps also the likelihood of acquiring infection.

The BCG vaccine is a live-attenuated strain derived from an isolate of Mycobacterium bovis and originally designed to prevent tuberculosis. It is estimated that over 130 million children were vaccinated with BCG every year in the world. 8 In addition to the specific effect against tuberculosis, BCG is known to elicit non-specific immune effects through the induction of the innate immune responses and the enhanced production of pro-inflammatory cytokines, such as IL-1β, tumor necrosis factor (TNF) and IL-6, to protect against a wide range of other infections. 2 

recent ecological studies have shown lower numbers of SARS-CoV-2 infections and reduced COVID-19 deaths in BCG-vaccinated countries when compared with BCG-non-vaccinated countries. 6 Kinoshita and the colleagues found the prevalence of the SARS-CoV-2 infection was inversely associated with BCG vaccine coverage in Japan. 13 However, ecological studies were based on population rather than individual data and thus were likely to be biased by confounding factors. 

symptoms in the healthy volunteers who either received BCG in the last 5 years or did not. None of the BCG-vaccinated or control individuals were admitted to hospitals, suggesting that BCG vaccination might not be associated with increased risk of hospitalization during the pandemic in this population. 14 The results from the phase III ACTIVATE trial showed that BCG vaccination was safe and could protect the elderly against infections, especially respiratory tract infections of probable viral origin, in the, and no difference in the frequency of adverse effects was found between the BCG and placebo groups, while larger studies are needed to further access this. 3 Nonetheless, since BCG vaccine is a live-attenuated vaccine, a potentially lethal infection could be expected in HIV-infected or immunocompromised individuals.

There are currently RCTs underway or being planned in the Netherlands, Australia, Greece, United States, Germany, Denmark, France, Poland, Egypt, South Africa, India, Iran, Brazil, and Canada to assess BCG vaccine and VPM1002 vaccine (a genetically modified BCG vaccine) and their efficacy in COVID-19 prevention and/or severity reduction. (Table) However, the size of those trials are smaller than those of the SARS-CoV-2 specific vaccines and the results should be compared with caution. If the RCTs could further provide more solid evidence to support the hypothesis, which the induction of innate immune responses or even specific immunity directly against SARS-CoV-2 by BCG vaccine could provide protection against COVID-19, BCG vaccination may be able to serve as an adjunct or alternate and lower-cost option for COVID-19 as the supply and stock are sufficient. 

Non-specific effects of BCG vaccine on viral infections

ACTIVATE: randomized clinical trial of BCG vaccination against infection in the elderly

Strong homology between SARS-CoV-2 envelope protein and a Mycobacterium sp. antigen allows rapid diagnosis of Mycobacterial infections and may provide specific anti-SARS-CoV-2 immunity via the BCG vaccine

Bacillus Calmette-Guérin vaccination and clinical characteristics and outcomes of COVID-19 in Rhode Island, United States: a cohort study

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

SARS-CoV-2 Rates in BCG-Vaccinated and Unvaccinated Young Adults

BCG-induced trained immunity: can it offer protection against COVID-19?

Funding source: none.

Literature search: Weng, Chan Study design: Weng, Chan Writing: Weng, Chan