Comprehensive analysis of the key epidemiological parameters to evaluate the impact of BCG vaccination on COVID-19 pandemic

Globally, the heterogenous coronavirus disease 2019 (COVID-19) case fatality rate (CFR) could be influenced by various epidemiological parameters. Identifying these could help formulate effective public health strategies. Incidence and mortality of COVID-19 for each of the 220 countries as on July 30, 2020 were evaluated against key epidemiological variables, namely - BCG vaccination (ongoing vs. discontinued/never undertaken), %population aged [&ge;]65 years, incidences of ischemic heart disease (IHD), hypertensive heart disease (HHD), cancer, malaria, and diabetes; human development index (HDI) and population density. These were retrieved from the public domains of WHO, UN, World Bank and published reports. The COVID-19 CFRs ranged between 0.0% and 28.3% (mean {+/-} SD: 3.05% {+/-} 3.48). The influence of the individual epidemiological parameters on CFR were evaluated through the event rate estimations. A significantly lower event rate was observed in countries with ongoing BCG vaccination program (ER: with vs without ongoing BCG vaccination: 0.020 vs 0.034, p<0.001). The type of BCG strains used also influenced the ER; this being 0.018, 0.031 and 0.019 for early, late and mixed strains respectively (p=0.008). The epidemiological variables significantly associated with higher COVID-19 event rate were countries with higher %population aged [&ge;]65 years (p<0.001), greater incidence of IHD (p<0.001) and cancer (p=0.003) and better HDI (p=0.003). Incidences of malaria, HHD and diabetes along with population density had no significant impact on COVID-19 CFR. Further, BCG vaccination significantly lowered the COVID-19 ER in each of the high-risk population subgroups - countries with >7.1% population aged [&ge;]65 years (p=0.008), >0.737 HDI (p=0.001), IHD >1171/105 population (p=0.004) and cancer incidence >15726 (p<0.001). The results supports BCG induced "trained immunity" leading to heterologous immunoprotection against COVID-19. Thus BCG vaccination with early strains could provide a cost-effective prophylaxis, especially in high-risk individuals and bridge the gap till an effective vaccine against SARS-CoV-2 is freely available globally.