TB–COVID-19 Co-Infection: Epidemiology, Mechanistic Crosstalk, and Therapeutic Challenges

Tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are among the most significant respiratory diseases, and their significant syndemic interaction in epidemiology during the pandemic period has raised severe global healthcare concerns. Disruption of TB control programs, potential co-infection and common risk factors underscore the need for a systematic assessment of the connection between these diseases. We summarize the current information regarding the relationship between tuberculosis (TB) and COVID-19 during and following the pandemic, including epidemiology; potential pathophysiological connections between SARS-CoV-2 infection and TB; clinical outcomes; and the implications for management. Global estimates of the burden of both diseases are reviewed, along with reported rates of TB–COVID-19 co-infection and associated mortality. The authors discuss mechanistic aspects of Mycobacterium tuberculosis and SARS-CoV-2 immune responses, including how these infections could modulate host immunity, thus impacting susceptibility and outcomes of disease upon co-infection. This review additionally discusses mutually shared risk factors and the broader implications of the COVID-19 pandemic on TB diagnosis, treatment sustainability and public health initiatives. The review also includes current therapeutic approaches and preventive strategies such as vaccination and integrated disease management. Overall, the evidence indicates that the overlap of TB and COVID-19 presents significant diagnostic, clinical and broader public health challenges, especially in settings of high burden. To reduce the combined burden of these infections and restore momentum towards global TB control targets, strengthening surveillance and respiratory disease management, as well as research on immune interactions and long-term outcomes will be the key.