BCG Correlation with Latent Tuberculosis Can Lead to Spurious Correlation with Reduced COVID-19 Mortality

Abstract

Background: Many factors have been suggested to confound coronavirus disease 2019 (COVID-19) studies, and BCG studies have been criticized for not adjusting for many confounders. We conducted this study to analyze the presumed effectiveness of the Bacillus Calmette–Guérin (BCG) vaccine in decreasing the COVID-19 mortality rate, and to answer the question of whether this is confounded by latent tuberculosis (LTB) prevalence. Materials and Methods: We chose sixty-nine malaria-free countries with different BCG vaccination policies. TB prevalence was considered as a proxy for LTB. The BCG, TB prevalence, and COVID-19 mortality data are publically available. Contingency coefficients (C.C.) and a Receiver Operating Characteristic (ROC) analysis were used to assess the relationship between TB prevalence and BCG status, and identify cutoff points in each BCG group category. A stem–leaf plot was also used to explore the data’s apparent behavior concerning COVID-19 in relation to the BCG groups. Results: TB prevalence was significantly associated with BCG status. There was a highly significant association according to (C.C.)  between TB prevalence and BCG group categories. Countries not implementing BCG vaccinations had low TB prevalence, and vice versa (p value = 0.000). ROC analyses indicating that BCG group is significantly associated with corresponding TB prevalence. Conclusions: BCG country status has a highly significant relationship with TB prevalence. This can  confound BCG and COVID-19 mortality and morbidity studies. In the absence of a correlation ,this can lead to a spurious correlation between BCG and reduced COVID-19 mortality or morbidity.