BCG Vaccine-Induced Trained Immunity and COVID-19: Protective or Bystander?

Abstract

In late 2019, a new virulent coronavirus (CoV) emerged in Wuhan, China and was named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This virus spread rapidly, causing the coronavirus disease-2019 (COVID-19) pandemic. Bacillus Calmette-Guérin (BCG) is a live attenuated tuberculosis (TB) vaccine, associated with induction of non-specific cross-protection against unrelated infections. This protection is a memory-like response in innate immune cells (trained immunity), which is caused by epigenetic reprogramming via histone modification in the regulatory elements of specific genes in monocytes. COVID-19 related epidemiological studies showed an inverse relationship between national BCG vaccination policies and COVID-19 incidence and death, suggesting that BCG may induce trained immunity that could confer some protection against SARS-CoV-2. As this pandemic has put most of Earth's population under quarantine, repurposing of the old, well-characterized BCG may ensure some protection against COVID-19. This review focuses on BCG-related cross-protection and acquisition of trained immunity, as well as the correlation between BCG vaccination and COVID-19 incidence and mortality.

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.…”

COVID-19 among staff and their family members of a healthcare research institution in Bangladesh between March 2020 and April 2021: a test-negative case–control study

“…Reports showed that nations with mandatory BCG vaccination had fewer numbers of patients with COVID-19. 20 22 Therefore, induction of trained immunity through BCG vaccination was thought to be a potentially effective approach to protect against SARS-CoV-2 infection. 20–24 We did not observe any association between COVID-19 infection and BCG vaccination.…”

“… 20 22 Therefore, induction of trained immunity through BCG vaccination was thought to be a potentially effective approach to protect against SARS-CoV-2 infection. 20–24 We did not observe any association between COVID-19 infection and BCG vaccination. BCG vaccination coverage is high in Bangladesh and we observed that 82% of both the COVID-19 positives and negatives had BCG scars in the upper arm.…”

“… 17–19 Few studies suggest that the bacille Calmette-Guerin (BCG) vaccination could be protective against COVID-19 infection as countries with compulsory BCG vaccination had fewer COVID-19 cases. 20–24 …”

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

“…BCG vaccination may modulate antiinflammatory cytokine and chemokine responses, resulting in fewer hospitalizations and lesser COVID-19 events. According to studies, countries that use BCG in their national vaccination programs (BCG countries) have fewer reported COVID-19 cases per million people than countries that do not use BCG [ 57 ]. In addition to the effect of BCG vaccinated to be associated a decrease in the incidence of sickness during the COVID-19 pandemic, co-administration of BCG and SARS-CoV-2 vaccines may have synergistic protective effects, including increased efficacy and/or duration of the memory response [ 58 ].…”