Case series: Treatment of COVID-19 with convalescent plasma in B-cell depletion

ABSTRACT

Background: Anti-CD 20 therapy is widely used in the treatment of autoimmune and hematological diseases. An absent antibody response to COVID-19 puts patients at high risk for a poor outcome or a protracted disease course. These patients may benefit from antibody-based therapy. We describe our experience with convalescent plasma (ConvP) as a source of antibody-based therapy in 5 consecutive B-cell depleted patients admitted with COVID-19. Methods: B-cell depleted patients with PCR confirmed COVID-19, symptomatic for at least 12 days were informed about the possibility of ConvP therapy. ConvP was selected based on virus neutralizing antibody titers (PRNT50 using a whole SARS-CoV-2 neutralization assay) of 1160 or higher. 300 or 600mL was transfused and in non-responders 600ml ConvP was repeated when no clinical response was observed. SARS-CoV-2 antibodies (Wantai ELISA detecting SARS-CoV-2 RBD antibodies and PRNT50) were measured preceding and after transfusion. Results: 5 B-cell depleted patients were admitted to a general COVID-19 ward. B-cell depletion was the result of rituximab (n=4) and blinatumomab (n=1) for lymphoma, auto-immune disease or Acute Lymphoblastic Leukemia. They had been sick with COVID-19 for a median of 33 days (Range 13-84 days). All had a serum PRNT50 titer <120 and were without detectable antibodies against RBD by a Wantai ELISA on the day of transfusion. 1 patient received 300mL and 4 patients received 600mL of ConvP on day 1 with a median PRNT50 titer in donor plasma of 1640 (Range 1160-11280). All patients showed obvious clinical improvement after the first transfusion. All patients also showed pulmonary improved on a chest CT-scan. All patients seroconverted with a median PRNT50 24 hours after transfusion of 140 (Range 120-180) and a median positive Wantai total Ig OD ratio of 12.63 (range 3,55-18,39) (Figure 1). PCR became negative in all patients within 16 days after transfusion and isolation could be lifted at that time. Conclusion: We observed prompt clinical and virological recovery after therapy with ConvP of B-cell depleted patients with a very protracted COVID-19 disease course. Our observation provide a proof of concept that in carefully selected patients, antibody-based therapy can be very effective. 24 hours after the transfusion of 600mL of ConvP, all patients had seroconverted to a PRNT50 titer of 120 to 180. We therefore suggest an initial dose of 600mL of ConvP with a PRNT50 of at least 1320.