Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created a remarkable and varying impact in every country, inciting calls for broad attention. Recently, the Bacillus Calmette-Guérin (BCG) vaccination has been regarded as a potential candidate to explain this difference. Herein, we hypothesised that the past epidemic of Mycobacterium tuberculosis (M. tuberculosis) may act as a latent explanatory factor for the worldwide differences seen in COVID-19 impact on mortality and incidence. We compared two indicators of past epidemic of M. tuberculosis, specifically, incidence (90 countries in 1990) and mortality (28 countries in 1950), with the mortality and incidence of COVID-19. We determined that an inverse relationship existed between the past epidemic indicators of M. tuberculosis and current COVID-19 impact. The rate ratio of the cumulative COVID-19 mortality per 1 million was 2.70 (95% confidence interval [CI]: 1.09-6.68) per 1 unit decrease in the incidence rate of tuberculosis (per 100,000 people). The rate ratio of the cumulative COVID-19 incidence per 1 million was 2.07 (95% CI: 1.30-3.30). This association existed even after adjusting for potential confounders (rate of people aged 65 over, diabetes prevalence, the mortality rate from cardiovascular disease, and gross domestic product per capita), leading to an adjusted rate ratio of COVID-19 mortality of 2.44, (95% CI: 1.32-4.52) and a COVID-19 incidence of 1.31 (95% CI: 0.97-1.78). After latent infection, Mycobacterium survives in the human body and may continue to stimulate trained immunity. This study suggests a possible mechanism underlying the region-based variation in the COVID-19 impact.
Highlights
The ongoing novel coronavirus disease 2019 (COVID-19) pandemic, precipitated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while a major concern, remains a mystery that puzzles the world
High COVID-19 mortality and incidence were observed in countries that had lower experiences of a past epidemic of M. tuberculosis, 30 and 70 years ago
Trained immunity due to latent persistent infection of M. tuberculosis is one of the potential contributors to the low mortality and incidence of COVID-19 seen in Asian countries, contrary to that of American and European countries
Summary
The ongoing novel coronavirus disease 2019 (COVID-19) pandemic, precipitated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while a major concern, remains a mystery that puzzles the world. In the early twentieth century, tuberculosis was on the rampage of prevalence in East Asian countries including Taiwan, Thailand, Vietnam, and Japan, wherein the cumulative mortality rates for COVID-19 were remarkably lower than those in other countries such as Spain, Italy, United Kingdom, and the United States of America (USA) In the latter countries, the tuberculosis burden, regardless of whether infection rate or mortality rate, was much lower than that in the former countries. "In countries wherein BCG vaccination is currently in place, the impact (mortality and incidence) of COVID-19 may be limited because the high-risk elderly population was infected with tuberculosis in younger days to get trained immunity. Current BCG vaccination would indicate a spurious relationship to reflect the past tuberculosis epidemic and an epiphenomenon to produce a spurious relationship with the fewer impact of COVID-19, which is seen in some countries, including Japan." We tested this hypothesis by comparing the cumulative mortality and incidence of COVID-19 with that of past epidemic of M. tuberculosis (the tuberculosis incidence of 90 countries in 1990 and tuberculosis mortality of 28 countries in 1950)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
