Abstract
Despite of the rapid development of the vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it will take several months to have enough doses and the proper infrastructure to vaccinate a good proportion of the world population. In this interim, the accessibility to the Bacille Calmette-Guerin (BCG) may mitigate the pandemic impact in some countries and the BCG vaccine offers significant advantages and flexibility in the way clinical vaccines are administered. BCG vaccination is a highly cost-effective intervention against tuberculosis (TB) and many low-and lower-middle-income countries would likely have the infrastructure, and health care personnel sufficiently familiar with the conventional TB vaccine to mount full-scale efforts to administer novel BCG-based vaccine for COVID-19. This suggests the potential for BCG to overcome future barriers to vaccine roll-out in the countries where health systems are fragile and where the effects of this new coronavirus could be catastrophic. Many studies have reported cross-protective effects of the BCG vaccine toward non-tuberculosis related diseases. Mechanistically, this cross-protective effect of the BCG vaccine can be explained, in part, by trained immunity, a recently discovered program of innate immune memory, which is characterized by non-permanent epigenetic reprogramming of macrophages that leads to increased inflammatory cytokine production and consequently potent immune responses. In this review, we summarize recent work highlighting the potential use of BCG for the treatment respiratory infectious diseases and ongoing SARS-CoV-2 clinical trials. In situations where no other specific prophylactic tools are available, the BCG vaccine could be used as a potential adjuvant, to decrease sickness of SARS-CoV-2 infection and/or to mitigate the effects of concurrent respiratory infections.
Highlights
Tuberculosis (TB) is a respiratory disease caused by Mycobacterium tuberculosis complex [1], a group of bacteria which primarily attacks the lungs along with other body parts such as the kidneys, spine, and brain
Bacillus Calmette-Guérin (BCG) vaccination has been effective for nearly a century against Tuberculosis (TB), but it has been described to reduce childhood mortality in a non-specific manner [6, 56, 57]
The Bacille Calmette-Guerin (BCG) is a live-attenuated vaccine that represents the most widely used vaccine in the world, with more than 4 billion people vaccinated with BCG worldwide and another 100 million newborn children vaccinated with BCG each year, providing over 50% protection against lung respiratory diseases and over 80% protection against disseminated TB [8]
Summary
Tuberculosis (TB) is a respiratory disease caused by Mycobacterium tuberculosis complex [1], a group of bacteria which primarily attacks the lungs along with other body parts such as the kidneys, spine, and brain. This prospective, randomized, double-blind study is testing the potential of BCG to affect (a) clinical evolution of COVID-19, (b) elimination of SARS-CoV-2 at different times and disease phenotypes, and (c) seroconversion rate and titration (antiSARS-CoV-2 IgA, IgM, and IgG) Such therapeutic vaccination strategy addresses the hypothesis that the induction of both innate and viral-specific immune responses might be beneficial during active SARS-CoV-2 antigenic exposure and provides further rationale for combining BCG-based vaccines with other approved vaccines. Further demonstrating complex interplay between innate and adaptive immunity, a randomized clinical trial of topical BCG in children having common warts caused by the human papillomavirus, showed 65% complete responses, with no response detected in the control group [38] These preliminary studies suggest that BCG vaccination could enhance vaccine induced immunity against SARS-CoV-2. This represents a unique approach that does not use a cow-derived attenuated M. bovis strain but a human-derived M. tuberculosis with deletion of phoP and faD25 genes, which is currently under clinical trial
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