A nationwide study suggests that severe COVID-19 infections may make some survivors more vulnerable to tuberculosis, highlighting the potential role of targeted screening after hospitalization.
Study: Risk of developing tuberculosis after severe coronavirus disease (COVID-19): a national cohort study. Image credit: Tatiana Shepeleva / Shutterstock
In a recent article in a magazine nature communicationsresearchers assessed the risk of developing tuberculosis (TB) after severe coronavirus disease 2019 (COVID-19) in Chilean adults.
In 2024, approximately 10.7 million people worldwide will be infected with tuberculosis and 1.2 million will die. Tuberculosis control efforts have been significantly disrupted by the coronavirus disease (COVID-19) pandemic, leading to approximately 500,000 excess tuberculosis deaths from 2020 to 2022. Before COVID-19 vaccines were available, nearly 14% and 5% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections caused severe and critical illness, respectively.
Severe coronavirus disease (COVID-19) is characterized by an exaggerated inflammatory response that can persist beyond the acute phase, causing transient immunosuppression and increasing susceptibility to secondary infections. Increasing evidence suggests that COVID-19 survivors may be at increased risk of reactivation of Mycobacterium tuberculosis infection. However, population-level TB risk post-COVID-19 remains poorly defined.
About research
In this study, researchers assessed the association between COVID-19 severity and tuberculosis risk within one year of COVID-19 diagnosis in a national cohort in Chile. This retrospective cohort study included adults aged 18 years and older with a primary SARS-CoV-2 infection confirmed by antigen testing or reverse transcription-polymerase chain reaction (RT-PCR).
People who died on the day they were diagnosed with SARS-CoV-2, people over 100 years of age, people with pre-COVID-19 tuberculosis, and people who were immunocompromised or on immunosuppressive treatment were excluded. The severity of COVID-19 infection was stratified into categories: non-hospitalized, hospitalized, and intensive care unit (ICU) admission. The study’s findings showed that new-onset tuberculosis occurs within one year of diagnosis of COVID-19. The team estimated the length of stay at risk from COVID-19 diagnosis to onset of tuberculosis, death, or end of follow-up.
Kaplan-Meier curves generated time to tuberculosis across severity categories. Cause-specific hazard ratios (HRs) for developing tuberculosis were estimated using Weibull regression models. We evaluated changes in effectiveness due to new coronavirus vaccination. A directed acyclic graph was constructed to explore potential confounds and guide model specification. Additionally, multiple sensitivity analysis was performed to assess the robustness of the results.
Survey results
The study included 3.6 million adults diagnosed with SARS-CoV-2 infection from March 2020 to October 2022. The median age of the cohort was 40 years, and 53.2% were female. Most subjects (94.2%) were not hospitalized, but 2.8% were hospitalized and 3.1% were admitted to the ICU. Most people (82.7%) were covered by the public health insurance system.
More than half of the cohort had pre-existing medical conditions, including diabetes (5.2%), chronic kidney, liver, and lung comorbidities (3.2%), and other comorbidities (46.1%). Only 16.5% of the cohort had completed their SARS-CoV-2 vaccination regimen before SARS-CoV-2 infection was confirmed. Over 3.6 million person-years of follow-up, new-onset tuberculosis was detected in 733 people within a year of COVID-19 diagnosis. These people were more likely to be older, male, immigrants, or have significant chronic comorbidities compared to people without TB.
The median time from COVID-19 diagnosis to tuberculosis was 127 days, with more than a third of cases occurring within the first two months of COVID-19 infection. Overall, new-onset TB remained rare, affecting 0.02% of the cohort, but 54,474 participants were censored due to non-TB deaths during follow-up. Regardless of ICU admission, people who required hospitalization for COVID-19 had a higher risk of tuberculosis than those who were not hospitalized. The adjusted hazard ratio for developing TB was 8.9 (95% confidence interval (CI): 7.28 to 10.94) for hospitalized cases and 8.3 (95% CI: 6.71 to 10.28) for ICU admitted cases.
Notably, this excess relative risk decreased over time but remained elevated. Additionally, men, immigrants, people in the public health system, and people with severe chronic comorbidities were at higher risk of developing TB. The researchers observed changes in effectiveness depending on vaccination status. Although the association between severe COVID-19 infection and new-onset tuberculosis was significantly stronger in unvaccinated people but significantly weakened in vaccinated people, the authors cautioned that this should not be interpreted as evidence that SARS-CoV-2 vaccination directly prevents tuberculosis.
Shortening the follow-up period to 6 months nearly doubled the magnitude of the association observed at 1 year. Calendar period analysis suggested that the association between severe COVID-19 and tuberculosis became stronger after corticosteroids became widely used to treat severe COVID-19, but this did not prove an individual treatment effect. Age-stratified analyzes revealed stronger associations for individuals younger than 50 years compared to those older than 50 years. In analyzes that excluded early TB events (i.e., TB events within 30 to 180 days after onset of COVID-19 infection), the effect estimates gradually decreased as the exclusion threshold increased. Finally, several sensitivity analyzes yielded consistent effect estimates.
conclusion
In summary, the observational design did not allow us to establish a causal relationship, and although the absolute incidence of TB was low, severe COVID-19 infections had a higher risk of developing TB within 1 year than non-severe COVID-19 infections. Relative TB risk decreased over time but remained elevated, suggesting that acute and post-acute phases of COVID-19 infection may compromise lung integrity and host immunity.
The authors noted that this association may reflect biological effects related to COVID-19 or underlying biological or social vulnerabilities. Targeted screening for latent and active TB infection among survivors of severe COVID-19, especially those with comorbidities such as diabetes or who have not received prior SARS-CoV-2 vaccination, could help reduce the burden of TB.
Want to read it later? Click here to download a PDF copy.
Reference magazines:
- Vargas-Garcia S, Garcia-Garcia L, Garcia C, et al. (2026). Risk of developing tuberculosis after severe novel coronavirus infection (COVID-19): a national cohort study. Nature Communications, press article. Doi: 10.1038/s41467-026-74528-5, https://www.nature.com/articles/s41467-026-74528-5
