Impact of Rituximab on COVID-19 in Immunocompromised Patients: A Nationwide Cohort Study in Korea

Background Anti-CD20 therapy has been associated with severe pneumonia in coronavirus disease 2019 (COVID-19) patients. This study aimed to evaluate the impact of anti-CD20 therapy on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related outcomes using a nationwide cohort.Methods We used the K-CoV-N database, integrating the Korea Disease Control and Prevention Agency and the National Health Insurance Service. Adults (>= 19 years) diagnosed with conditions warranting anti-CD20 therapy from January 2020 to December 2021 were included. Patients initiating rituximab (RTX) during the study period were defined as RTX users, whereas RTX nonusers were selected through propensity score matching. Logistic regression analyses were used to estimate the association between RTX use and SARS-CoV-2 infection, as well as COVID-19-related outcomes.Results Among 1 548 038 patients requiring anti-CD20 therapy, 1 457 171 were vaccinated and 90 867 were unvaccinated. In the vaccinated group, RTX use was not significantly associated with an increased risk of SARS-CoV-2 infection (adjusted odds ratio [aOR] 1.75; 95% confidence interval [CI], .82-3.72; P = .149) but was linked to higher hospitalization for COVID-19 (aOR 2.64; 95% CI, 1.14-6.10; P = .024) and intensive care unit admission (aOR 10.89; 95% CI, 1.44-82.46; P = .021). In the unvaccinated group, RTX use showed no statistically significant associations with severe COVID-19 outcomes.Conclusions Using a nationwide dataset, this study found that RTX use is associated with an increased risk of severe COVID-19 outcomes in vaccinated individuals. Despite rising vaccination rates, clinicians should carefully weigh the risks and benefits of anti-CD20 therapy during the COVID-19 pandemic. Using a nationwide dataset, the impact of anti-CD20 therapy on COVID-19-related outcomes was analyzed. Rituximab use increases the risk of severe COVID-19 outcomes in vaccinated individuals. Clinicians should carefully weigh the risks and benefits of anti-CD20 therapy during the COVID-19 pandemic.