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 1:160 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 <1:20 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 1:640 (Range 1:160-1:1280). 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 1:40 (Range 1:20-1:80) 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 1:20 to 1:80. We therefore suggest an initial dose of 600mL of ConvP with a PRNT50 of at least 1:320.
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 1:160. 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 1:640 (IQR 1:160-1:1280). 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 <1:20 preceding transfusion to 1:40 (IQR 1:20-1:80) 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 1:20 or higher. Based on these observations, we suggest an initial dose of 600mL of ConvP.