Background: The coronavirus SARS-CoV-2 (COVID-19) experience has underscored the consequences of inequalities in health and access to health services across and within countries. Vulnerable population groups have been disproportionately exposed to certain diseases such as tuberculosis (TB) due to service interruptions. The current study aimed to assess TB related mortality and risk of drug resistance during the COVID-19 Pandemic in Burundi. Methods: We conducted an incident case–control study on 362 TB patients, with 181 multidrug resistant TB (MDR-TB) patients and 181 drug susceptible TB (DS-TB) patients. These patients under TB treatment between July 11, 2018, and November 11,2022 (18 months before and 18 months during COVID-19). Baseline and drug susceptibility status data were captured at treatment initiation. Mortality during treatment follow-up TB mortality was compared between categories of drug susceptibility, period (before vs during COVID-19) and regimen phase. A multivariate logistic regression was used to show the predictive risk factors. K-Fold cross-validation was used to evaluate the final model. Results: A half of TB patients was under 40 years old, with majority of them being unemployed, malnourished and lacking food support during TB treatment. Most of them lived in precarious conditions with limited access to healthcare services. The overall TB-related mortality was 16.0% (95% CI: 12.5%- 20.3%) with 15.5% (95%CI: 10.7%-21.8%) in MDR-TB patients and 16.6% (95% CI: 11.6%-22.9%) in DS-TB patients. Stratified by the period, TB related mortality was 15.3% (95%CI: 11.7%-20.9%) before the COVID-19 pandemic and 17.1% (95%C 11.5%-24.6%) during the COVID-19 pandemic. More than a half of deaths in TB patients occurred during intensive phase of treatment. The risk of MDR-TB was significantly higher (p < 0.05) among patients undergoing treatment during the pandemic, those with a low education level, living in rural areas, unemployed, using public transportation, or living in overcrowded households (big family size,a small number of rooms). Additionally, patients with history of TB, previous treatment failure, and close contact with MDR-TB patients were more likely to have MDR-TB. The likelihood of MDR-TB further increased with the cumulative presence of these risk factors on the same TB patient. Conclusion: TB mortality increased during the COVID-19 pandemic, particularly among MDR-TB patients. The odds of MDR-TB encompass a range of socio demographic and clinical factors particularly among economically disadvantaged patients. These findings underscore the need for targeted equity-driven interventions in high-risked populations, especially in the context of emerging outbreaks, in order accelerate TB elimination goals. Additional investigation on TB related mortality should focus on the intensive phase of treatment, which aligns with the 2025 World Health Organization consolidated guidelines on TB diagnosis and control. [ABSTRACT FROM AUTHOR]

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