The BCG Vaccine for COVID-19: First Verdict and Future Directions

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.

Effectiveness of booster BCG vaccination in preventing Covid-19 infection

“…Two recent review articles provided an effective overview of current literature and understanding of BCG and COVID-19. 13 , 14 They review early epidemiological studies, as well as provide an overview of ongoing clinical trials, and importantly conclude that the results of these ongoing clinical trials will be important in confirming data from ecological studies and small observational studies such as this one. Trained immunity induced by vaccines such as BCG may be an important bridge before more widespread availability of specific vaccines, possibly an effective adjunct alongside specific vaccines, and likely an important tool in future viral pandemics.…”

Roles of existing drug and drug targets for COVID-19 management

“…Despite the rapid development of SARS-CoV-2 vaccines, it took several months to produce enough doses and the resources needed to vaccinate a large portion of the global population. In the meantime, in some countries, access to the Bacille Calmette-Guerin (BCG) vaccine may help to mitigate the pandemic's effects [ 55 ]. The BCG tuberculosis vaccine is a live attenuated strain derived from a Mycobacterium bovis isolate.…”

COVID-19 and Beyond: Exploring Public Health Benefits from Non-Specific Effects of BCG Vaccination

“…Numerous trials investigating the potential of BCG vaccination to fight the COVID-19 pandemic are currently underway, incorporating diverse strains of BCG and potentially providing further insight into optimal strain selection. Two prior reviews have cataloged these studies, and more up-to-date information for some trials can be accessed at (accessed on 1 September 2021) [ 121 , 122 ]. Here, we discuss studies BCG studies with COVID-19 as their primary disease that are currently listed as recruiting, not yet recruiting, and active.…”