The lower than expected number of SARS-CoV-2 cases in countries with fragile health systems is puzzling. Herein, we hypothesize that BCG vaccination policies adopted by different countries might influence the SARS-CoV-2 transmission patterns and/or COVID-19 associated morbidity and mortality through the vaccine’s capacity to confer heterologous protection. We also postulate that until a specific vaccine is developed, SARS-CoV-2 vulnerable populations could be immunized with BCG vaccines to attain heterologous nonspecific protection from the new coronavirus.
In January, World Health Organization (WHO) Director General Tedros Adhanom Ghebreyesus said his “greatest concern” was COVID-19 spreading in countries with fragile health systems. Although countries like India, Philippines, Sri Lanka, Cambodia, Thailand, Vietnam and Nepal have reported their first confirmed cases of the SARS-CoV-2 virus in January, widespread examples of community spread have not been reported. In fact, contrary to such justified expectations/predictions, on March 13 2020, WHO declared that “Europe has now become the epicenter of the pandemic, with more reported cases and deaths than the rest of the world combined”. Even though we are still in the midst of this novel coronavirus pandemic and the situation might drastically change in coming days, the disproportionately smaller number of cases reported from disadvantaged/low income countries remains puzzling. We hypothesize that general BCG vaccination policies adopted by different countries might have impacted the transmission patterns and/or COVID-19 associated morbidity and mortality.
Ordinarily, a vaccine provides protection from a particular pathogen, by inducing effector mechanisms directed to that pathogen. However, certain live attenuated vaccines like the Bacillus Calmette–Guerin (BCG), an attenuated strain of Mycobacterium bovis, provide protection not only to a specific pathogen, but also against unrelated pathogens, some of which cause acute respiratory tract infections., , , , , ,  The underlying mechanism for the BCG vaccination-induced non-specific protection is thought to be mediated via the induction of innate immune memory, or “trained immunity, as was first proposed by Netea and collaborators. Trained-immunity inducing agents reprogramme bone marrow hematopietic stem cells and multipotent progenitors through epigenetic and metabolic changes, resulting in a more robust response in differentiated innate immune cells, following encounter with a pathogen.,  Of interest, in a randomized placebo-controlled human study, BCG vaccination was demonstrated to induce epigenetic reprograming in monocytes, conferring protection against experimental infection with an attenuated yellow fever virus vaccine strain.
Based on these observations, we hypothesized that countries who continue BCG immunization programs would contain the spread of this new coronavirus better than those that did not have or have ceased their national BCG vaccination programs. To check the validity of this hypothesis, we compared the number of cases and deaths per million people from 40 countries with at least 500 cases according to their BCG vaccination status (Figure 1 and Table 1 ). Case numbers per million people in countries with a national BCG vaccination programme were statistically significantly lower than those that did not have or have ceased their national BCG vaccination programs (P<0.0001). Since case numbers are dependent on SARS-CoV-2 testing capability of each country and might not be representative of the true extent of the regional epidemic, we also compared the number of deaths per million. Results showed that COVID-19 associated deaths relative to the size of the population were statistically significantly lower in countries with a national BCG vaccination programme than those that did not have or have ceased their national BCG vaccination programs (P<0.0058). The most affected country with the highest death toll was Italy, which historically never had a national BCG vaccination policy for all. Consistently, Italy also reports higher mortality rates compared to other countries.
Prof (Dr) Ratnesh Dwivedi is Vice Chancellor of Learnforth University,London and Member of Advisory Board,Life Boat Foundation ,an Highly acclaimed scientific research body of USA where Prof Dwivedi shares board with Nobel Laureates)
Prof (Dr) Ratnesh Dwivedi