COVID-19 Infection in Multiple Sclerosis Patients Treated with Rituximab Compared to Natalizumab and Healthy Controls: A Real-World Multicenter Study

Introduction: The impact of coronavirus disease 2019 (COVID-19) infection on patients with multiple sclerosis (MS) undergoing various immunomodulating therapies can vary. Individuals on B-cell therapy, such as rituximab, may be more susceptible to infection compared to those treated with natalizumab. Objective: The objective of this study was to determine the incidence and severity of COVID-19 infection in patients receiving rituximab, natalizumab, and healthy controls. Methods: This retrospective multicentric study included data derived from a centralized MS registry of four centers in South India. Data of patients on rituximab and natalizumab recruited between 2020 February and 2022 December were extracted from the registry and analyzed. The outcomes studied were the occurrence of COVID-19 infection, hospitalization, intensive care unit admission, death, post-COVID-19 relapses, and post-vaccine relapses. These outcomes were compared between the treatment groups and the matched controls. Results: COVID-19 infection occurred in 49.1% (26/53) of those on rituximab, 19.2% (5/26) of those on natalizumab, and 11.5% (6/52) of healthy controls. In addition, 8/53 (15.1%) in the rituximab group and 1/26 (3.8%) in the natalizumab group were hospitalized. All 6/52 (11.5%) in the control group had mild infection, and none were hospitalized. No deaths occurred in any group. On statistical analysis, the occurrence of COVID-19 infection in the rituximab group was significantly higher when compared to natalizumab ( P = 0.0141) and healthy controls ( P < 0.001). Hospitalizations were significantly higher in the rituximab group when compared to healthy controls ( P < 0.006). Conclusion: MS patients treated with rituximab were more likely to experience COVID-19 infection compared to those treated with natalizumab and healthy controls. Hospitalization was more frequently seen in patients treated with rituximab compared to healthy controls.