Short- and long-term increased risk of all-cause mortality in a tuberculosis cohort attributed to SARS-CoV-2 infection: a time-dependent survival analysis in Chile

Background Concurrent tuberculosis (TB) and COVID-19 increases the risk of mortality; however, most studies have focused primarily on short-term outcomes.We assessed the short and long-term impact of TB and SARS-CoV-2 coinfection on all-cause mortality.Methods We conducted a retrospective nationwide cohort study in Chile, including adults diagnosed with active TB from January 1st, 2020, to December 31st, 2021, with follow-up until November 30th, 2022.SARS-CoV-2 coinfection was defined as occurring from 30 days before to six months after TB diagnosis.Short-term mortality was defined as death within 90 days of TB or TB/SARS-CoV-2 diagnosis, and long-term mortality as death occurring after 90 days.We used a time-dependent Cox survival analysis, adjusting for sociodemographic factors, SARS-CoV-2 vaccination, and relevant comorbidities including HIV, diabetes and Mycobacterium tuberculosis drug-resistance status.Findings The cohort included 3721 adults (median age: 47 years, interquartile range [IQR]: 32-61); of whom 634% were male, and 794% had pulmonary TB.The median follow-up was 586 days (IQR: 401-820), with 680 deaths (183%) recorded.A SARS-CoV-2 coinfection was identified in 393 individuals (105%); the mortality in this group was higher in short-term (90 days: 145% vs. 114%) and long-term (>90 days: 115% vs. 59%) compared to TB alone.Coinfection increased the risk of all-cause mortality during the entire follow-up (aHR [adjusted Hazard Ratio]: 28, 95% CI: 226-347), over three-fold in the short-term (aHR 34, 95% CI: 257-451) and nearly two-fold in the long-term (aHR: 172, 95% CI: 118-252).Excess mortality persisted beyond the first year (aHR: 204, 95% CI: 109-382).SARS-CoV-2 vaccination reduced mortality risk in the TB cohort by 35% (95% CI: 19-46%).Interpretation Tuberculosis and SARS-CoV-2 coinfection was associated with significantly increased all-cause mortality in both the short and long-term, with elevated risk persisting beyond TB treatment completion.These findings highlight the need for continued post-treatment follow-up and prioritization of SARS-CoV-2 vaccination among individuals with TB.