Dissecting the effect of single- and co-infection of TB and COVID-19 pathogens on the sputum microbiome.

Tuberculosis (TB) and COVID-19 are both respiratory diseases, and understanding their interaction is important for effective co-infection management. Although some studies have investigated TB and COVID-19 co-infection in terms of immune responses, microbial dysbiosis in such cases remains unexplored. In this study, we understand the interface between TB and COVID-19 by systematically inspecting the microbial composition of sputum samples collected from four groups of individuals: TB only, COVID-19 only, and both TB and COVID-19 (TBCOVID) infected patients, and uninfected group (Controls). Besides metagenomic analysis of the microbiome of these sputum samples, we also performed whole-genome sequencing analysis of a subset of TB-positive samples. Different bioinformatic analyses ensured data quality and revealed significant differences in the microbial composition between Control vs disease groups. To understand the effect of COVID-19 on TB, we compared TBCOVID vs TB samples and observed (i) higher read counts of TB-causing bacteria in the TBCOVID group, and (ii) differential abundance of several taxa, including IMPORTANCE: The community of microbes in an individual's airway tract can play a complex role in respiratory diseases like tuberculosis (TB) and COVID-19. Although changes in microbial composition in TB and COVID-19 patients have been studied separately, we present a first-of-its-kind investigation of the airway-tract microbiome of individuals simultaneously infected with TB and COVID-19 pathogens. Our results highlight that co-infection with COVID-19 in TB patients alters the abundance of certain bacterial species and their related pathways. For instance,