Exercising caution in correlating COVID-19 incidence and mortality rates with BCG vaccination policies due to variable rates of SARS CoV-2 testing

Janine Hensel; Daniel J McGrail; Kathleen M McAndrews; Dara Dowlatshahi; Valerie S LeBleu; Raghu Kalluri

Our independent analysis of COVID-19 cases per million of inhabitant in 78 countries that were stratified based on the prevalence of BCG vaccination (universal vaccination policy) shows that, a priori, there is a correlation between current universal BCG vaccination policy and a lower incidence of CoV-2 infection and related deaths. However, we note that testing rates (tests per million inhabitants) was positively correlated with incidence of CoV-2 infection. Taking in consideration this important bias, we curated the data to compare the number cases amongst countries with distinct universal BCG policy based on high CoV-2 testing rates, as defined by 2,500 tests or more per million inhabitants. The results show a lack of significant difference in incidence of COVID-19 cases in countries with current universal BCG vaccination policy and countries with never-or in the past-universal BCG vaccination policy. Other variables tested included population density, percent urban population, percent migrants, median age, sex, time since the first confirmed COVID-19 case, percent smokers, and heart associated mortality. Urban population and median age were significantly associated with increased number of cases; however, their impact were not as significant as CoV-2 testing rates. Interestingly, COVID-19 associated mortality was decreased in countries with current universal BCG vaccination policy and similar CoV-2 testing rates. This may however reflect potential inaccuracies in reporting of COVID-19 mortalities due to lack of Cov-2 testing. Our study is limited by several critical considerations, which were not addressed here. These include the variability and inaccuracies in reporting positive cases and reporting specific mortality associated with CoV-2 infection, lack of reporting on asymptomatic or minimally symptomatic cases, the impact of social and economic barriers in accessing care, the association with other co-morbidities, and the adherence or access to vaccination as per policy. In this regard, a recent report showed a correlation of universal BCG vaccination policies and the number of COVID-19 cases when controlling for income [7] . This study however did not take in consideration CoV-2 testing rates. It is also possible that the lower rate of CoV-2 testing, combined with lower viral loads in traditionally warmer countries with higher incidence of tuberculosis, could impact our observations [8] .