Individual patient and donor seroprofiles in convalescent plasma treatment of COVID-19 in REMAP-CAP clinical trial

Abstract

Objectives: Convalescent plasma (CP) treatment of COVID-19 has shown significant therapeutic effect only when administered early. We investigated the importance of patient and CP seroprofiles on treatment outcome in REMAP-CAP CP trial.

Methods: We evaluated neutralising antibodies (nAb), anti-spike (S) IgM, IgG, IgG avidity, IgG fucosylation and respiratory viral loads in a sub-set of patients (n=80) and controls (n=51) before and after transfusion, comparing them to those in the CP units (n=157) they received.

Results: Most patients were SARS-CoV-2 seropositive pre-transfusion (72% nAb; 89% S-IgG seropositivity). The majority (80%) had higher pre-transfusion S-IgG levels (median 1.7×10⁶ arbitrary units (AU); 56%) or S-IgG production rates (median 1.1×10⁶ AU/day; 64%) than they received from CP (median 2.2×10⁵ AU). Only 22% of the patients demonstrated significant (median 24-fold) increase in their S-IgG levels acquired from transfusion. Better outcomes, measured by organ support-free days, were associated with increase in S-IgM levels (p=0.007), decreased S-IgG fucosylation (p<0.001), lower patient age (p<0.001) but not with receiving CP (p=0.337).

Conclusions: Based on our data, increased S-antibody levels linked to transfused CP were only observed in pre-seroconversion or immunodeficient patients lacking their own SARS-CoV-2 antibodies, representing the groups where CP treatment has previously shown most benefit.

Keywords: Antibodies; COVID-19; Convalescent plasma treatment; Critical care; Infectious diseases; SARS-CoV-2; Serology; Transfusion medicine; Virology.