Bacille Calmette-Guérin (BCG) vaccine and potential cross-protection against SARS-CoV-2 infection — Assumptions, knowns, unknowns and need for developing an accurate scientific evidence base

Abstract

After a century of controversies on its usefulness in protection against TB, underlying mechanisms of action, and benefits in various groups and geographical areas, the BCG vaccine is yet again a focus of global attention- this time due to the global COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have shown that human CD4+ and CD8+ T-cells primed with a BCG-derived peptide developed high reactivity to its corresponding SARS-CoV-2-derived peptide. Furthermore, BCG vaccine has been shown to substantially increase interferon-gamma (IFN-g) production and its effects on CD4 + T-cells and these non-specific immune responses through adjuvant effect could be harnessed as cross protection against severe forms of COVID-19.The completion of ongoing BGG trials is important as they may shed light on the mechanisms underlying BCG-mediated immunity and could lead to improved efficacy, increased tolerance of treatment, and identification of other ways of combining BCG with other immunotherapies.

Seroprevalence of SARS-CoV-2 infection and associated factors among Bangladeshi slum and non-slum dwellers in pre-COVID-19 vaccination era: October 2020 to February 2021

“…There is no solid evidence yet that the BCG vaccination protects against the infection. A number of studies have described broad cross-protective effects of the BCG vaccine toward diverse unrelated infections, which is believed to be mediated through induction of trained immunity or long-term maintenance of innate immune memory [ 39 , 40 ]. The WHO does not endorse BCG vaccination to protect against COVID-19; however, it plans to assess the findings of the ongoing clinical trials addressing this query.…”

Innate lymphoid cells exhibited IL-17-expressing phenotype in active tuberculosis disease

“…Globally, there were an estimated 10.0 million tuberculosis (TB)-infected patients and an estimated 1.2 million TB deaths in 2019 [ 1 ]. Controlling tuberculosis which is infected by Mycobacterium tuberculosis (Mtb) remains a thorny issue.…”

Role of multiple factors likely contributing to severity-mortality of COVID-19

“…S1) while for India, its temporal analysis showed co-dominance of multiple viral variants. While recognising the potential beneficial effects of BCG vaccination we agree with others who have urged that robust clinical trial evidence is needed before BCG vaccination can be recommended as an intervention to be applied on a wide scale for the prevention of COVID-19 morbidity and mortality ( Nachega et al, 2021 ). In fact, scientists are proposing the concept of “heterologous vaccine boosting” which means a non-specific vaccine as a boost, second dose after the COVID-19 specific vaccine prime dose, especially when the second dose of COVID-19 vaccine is unavailable.…”