BCG Vaccination and Mortality of COVID-19 across 173 Countries: An Ecological Study

Abstract

Ecological studies have suggested fewer COVID-19 morbidities and mortalities in Bacillus Calmette-Guérin (BCG)-vaccinated countries than BCG-non-vaccinated countries. However, these studies obtained data during the early phase of the pandemic and did not adjust for potential confounders, including PCR-test numbers per population (PCR-tests). Currently-more than four months after declaration of the pandemic-the BCG-hypothesis needs reexamining. An ecological study was conducted by obtaining data of 61 factors in 173 countries, including BCG vaccine coverage (%), using morbidity and mortality as outcomes, obtained from open resources. 'Urban population (%)' and 'insufficient physical activity (%)' in each country was positively associated with morbidity, but not mortality, after adjustment for PCR-tests. On the other hand, recent BCG vaccine coverage (%) was negatively associated with mortality, but not morbidity, even with adjustment for percentage of the population ≥ 60 years of age, morbidity, PCR-tests and other factors. The results of this study generated a hypothesis that a national BCG vaccination program seems to be associated with reduced mortality of COVID-19, although this needs to be further examined and proved by randomized clinical trials.

Keywords: BCG; Bacillus Calmette–Guérin; COVID-19; SARS-CoV-2; coronavirus disease 2019; ecological study; morbidity; mortality; urbanization; vaccination.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Histograms of morbidities and mortalities drawn as a normal density plot. (A) Morbidity per million; (B) mortality per million; (C) log10 transformed morbidity; and (D) log10 transformed mortality.

Figure 2

(A) Associations between morbidity, mortality and PCR-tests. Either Pearson’s correlation coefficient or Spearman’s rank correlation was applied to calculate rho; (B) associations between morbidity and risk factors were adjusted for PCR-tests per million population (log10); (C) associations between mortality and risk factors were adjusted for morbidity (log10) and PCR-tests (log10) per million population.

Figure 3

Scatter plot showing the association between PCR-test positivity and mortality. Mortality per million population and PCR-test positivity rates (%) on 17 July 2020 were transformed to the common logarithm (log10) in the graph. Since the variable of ‘PCR-test positivity (log10)’ showed a normal distribution, Pearson’s correlation coefficient was applied to calculate rho, to quantify the strength of the association. Countries that never had or stopped a national BCG vaccine program are indicated in red, while countries with current national BCG vaccine programs are indicated in black. Selected country names are shown using three-letter country codes.

Figure 4

Scatter plot showing the association between urban population and COVID-19 morbidity rates. COVID-19-related morbidity rates per million population on 17 July 2020 were transformed to the common logarithm (log10) in the graph. Since the variable of ‘urban population’ showed a non-normal distribution, Spearman’s rank correlation was applied to calculate rho, to quantify the strength of the association. Countries that had never had or that had stopped a national program of BCG vaccination are indicated in red, while countries that currently follow a national BCG vaccine program are indicated in black. Selected country names are shown using three-letter country codes.

Figure 5

Scatter plot showing the association between insufficient physical activity and COVID-19 morbidity rates.

Figure 6

Scatter plot showing the association between ≥60 years of age (%) of the population and mortality rate. Mortalities per million population on 17 July 2020 transformed to the common logarithm (log10) are presented in the graph. Since the variable of ‘percentage of population ≥ 60 years of age (%)’ showed a non-normal distribution, Spearman’s rank correlation was applied to calculate rho, to quantify the strength of the association. Countries that had never had or that had stopped their national BCG vaccine program are indicated in red, while countries that currently follow a national BCG vaccine program are indicated in black. Selected country names are shown using three-letter country codes.

Figure 7

Scatter plot showing the association between COVID-19-related mortality and BCG vaccine coverage. Mortalities per million population on 17 July 2020 are transformed to the common logarithm (log10) in the graph. Since the variable of ‘BCG vaccine coverage’ showed a non-normal distribution, Spearman’s rank correlation was applied to calculate rho, to quantify the strength of the association. Selected country names are shown using three-letter country codes.