Rebound and Protracted COVID-19 in Patients Receiving Rituximab for Autoimmune and Glomerular Diseases

Background: B cell depletion with rituximab abrogates antibody responses against SARS-CoV-2 and is associated with severe COVID-19. The risk and best treatment of rebound COVID-19 with recent strains of SARS-CoV-2 in patients using rituximab is unknown. Methods: We conducted a retrospective study of patients who developed COVID-19 between 5/25/23-3/1/24 while receiving rituximab at Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital. Patient characteristics, treatments, and outcomes of COVID-19 were evaluated. Results: A total of 48 patients were included. The median age was 62 (IQR 47–72). 63% (30/48) had ANCA-associated vasculitis. Patients received a median of 5 (IQR 3–6) vaccinations and had 1 (IQR 0–1) prior infection. The median time from the last rituximab dose to COVID-19 was 4.2 (IQR 1.5–11.1) months, and 88% (42/48) had B cell depletion. 19% (9/48) had moderate, severe, or critical disease per NIH symptom scale and required hospitalization. 85% (41/48) received treatment, including nirmatrelvir/ritonavir (56%), remdesivir (21%), and IVIG (4%) (Table 1). One patient died. 38% (18/48) developed rebound or protracted (>30 days) COVID-19, of whom all had full B cell depletion, 56% (10/18) developed at least moderate COVID-19, and 67% (12/18) received treatment (Table 1). 50% (9/18) were treated with IVIG adjunctive to antivirals, which raised serum anti-SARS-CoV-2 antibodies (Fig.1) and improved all except one who died. Conclusion: COVID-19 in B cell-depleted patients is associated with high rates of rebounding disease and hospitalization despite available treatments and vaccines. IVIG is effective as an adjunct strategy.