COVID-19 outcomes among vaccinated and unvaccinated patients receiving disease-modifying antirheumatic drugs and biologic therapies: a retrospective multihospital cohort study.

INTRODUCTION/OBJECTIVES: Patients receiving disease-modifying antirheumatic drugs (DMARDs) and biologic therapies were underrepresented in initial COVID-19 vaccine trials, limiting understanding of vaccine effectiveness in immunosuppressed populations. While immunogenicity studies demonstrate reduced antibody, real-world outcome-based evidence remains limited. We evaluated the association between COVID-19 vaccination and clinical outcomes among hospitalized patients receiving systemic DMARDs and biologic therapies. METHODS: We conducted a retrospective cohort study across seven hospitals within the UPMC health system in Central Pennsylvania. Adults (≥ 18 years) hospitalized with COVID-19 between March 2020 and April 2025 and receiving immunomodulatory therapy. Vaccination status was determined using electronic health records and registry-linked coding data, with vaccine type and SARS-CoV-2 variants also assessed. The primary outcome was hospital length of stay (LOS). The secondary outcome was in-hospital mortality. Multivariable logistic regression and gamma regression models adjusted for key demographic and clinical covariates. RESULTS: Among 254 patients, 144 were vaccinated and 110 were unvaccinated. One hundred twenty-eight vaccinated patients received at least one booster. Vaccinated had shorter median LOS (6 vs. 10 days; p < 0.0001), with a 37% reduction in LOS odds. Among vaccinated, those who received at least 1 booster had shorter LOS than those without a booster (6 vs. 7.5 days; p = 0.0414). In-hospital mortality was lower among vaccinated (6.25% vs. 27.27%; p < 0.0001), with an 84% reduction in odds of death (adjusted OR, 0.157; 95% CI, 0.068-0.361). CONCLUSION: Among hospitalized receiving DMARDs and biologic therapies, COVID-19 vaccination was independently associated with reduced mortality and shorter hospital length of stay, supporting vaccination as a critical protective strategy in immunosuppressed populations. Key Points • COVID-19 vaccination was independently associated with a 37% reduction in hospital length of stay among immunosuppressed patients receiving DMARDs or biologics. • Vaccinated patients experienced substantially lower in-hospital mortality (6.25% vs 27.27%), even after adjustment for clinical covariates. • Vaccination was associated with an 87% reduction in adjusted odds of death. • Findings support COVID-19 vaccination as protective in patients receiving DMARDs and biologic therapies.