Treatment of COVID-19 in 22 B-cell-depleted patients

ABSTRACT

Background: Anti-CD20 therapy is used to treat autoimmune and hematological diseases. An absent or delayed antibody response against SARS-CoV-2 puts patients at risk for a protracted and severe disease course. These patients may benefit from antibody-based therapy of which convalescent plasma (ConvP) is the most broadly available source. Methods: ConvP from donors with SARS-CoV-2 antibody titers was used when their plaque reduction neutralization test (PRNT50) showed a PRNT50 titer of at least 1160. When PRNT50 results were not yet available, an in-house RBD ELISA was used to select the donors with the 10% highest titers. Preceding and following transfusion, SARS-CoV-2 antibodies were measured (Wantai Ig SARSCoV-2 RBD antibodies and PRNT50). All but 6 patients received 2 units of 300mL of ConvP. Two non-responders received a second 2x300ml transfusion while 5 patients were successfully treated with only 300ml ConvP. Results: 22 B-cell depleted patients admitted with COVID-19 were treated with ConvP. B-cell depletion was the result of Rituximab (n=19), Obinutuzumab (n=1), XLA (n=1) or Blinatumomab (n=1) for lymphoma, auto-immune disease or ALL. Patients had been sick for a median of 26 days (IQR 18-34.5 days) and all were SARS-CoV-2 RBD antibody negative on the day of transfusion. The plasma units had a median PRNT50 titer of 1640 (IQR 1160-11280). 19 of 22 patients showed clear clinical improvement after transfusion and could be discharged from the hospital. 3 patients died of which 1 had treatment refractory extensive idiopathic pulmonary fibrosis preceding COVID-19. All patients seroconverted to a median total Wantai Ig OD ratio of 18.39 (IQR 11.245-18.41), Figure 1. PRNT50 titers increased from <120 preceding transfusion to 140 (IQR 120-180) after transfusion. One patient quickly recovered clinically after transfusion but it took 10 weeks to become PCR negative. Conclusion: Prompt clinical and virological recovery after ConvP transfusion was observed in the large majority of B-cell depleted antibody negative patients admitted with COVID-19. Our observation shows that for carefully selected patients, antibody-based therapy can be effective. After transfusion of 600mL of ConvP, all patients had seroconverted to high anti-RBD antibody titers and detectable PRNT50 titers of 120 or higher. Based on these observations, we suggest an initial dose of 600mL of ConvP.