Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection

Arvind Gharbharan,Jan G Den Hollander,Marco W J Schreurs,Jelle Miedema,Menno Van Der Eerden,Peter Te Boekhorst,Francis Swaneveld ,Corine H Geurtsvankessel ,A.s.m Dofferhoff ,Robert‐Jan Hassing ,Marion Koopmans ,Femke Mollema ,Carlijn Jordans ,Elena M Van Leeuwen-Segarceanu ,Janneke E Stalenhoef ,Nisreen M.a Okba ,Thijs J Schrama ,Jeroen J.a Van Kampen ,Jeannet C Bos,Grigorios Papageorgiou,Yvonne M Mueller,Faiz Karim,Adrianus Koster,Imro N Vlasveld,Inge Ludwig,Heidi S M Ammerlaan,Geert R Van Pottelberge,Barry Rockx,Peter D Katsikis,Casper Rokx,Bart L Haagmans,Bart Rijnders

doi:10.1038/s41467-021-23469-2

Abstract

In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARS-CoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development.

Highlights

In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARSCoV-2 antibodies, no overall clinical benefit was observed
A total of 204 patients from 14 Dutch hospitals with a reverse-transcriptase PCR (RT-PCR) confirmed SARS-CoV-2 infection and admitted for a moderate, severe, or life-threatening COVID-19 infection were screened for eligibility
Our study demonstrates that the administration of Convalescent plasma (ConvP) with high titers of virus-neutralizing antibodies does not benefit patients who are hospitalized for COVID-19 after 10 days post symptom onset

Summary

Introduction

In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARSCoV-2 antibodies, no overall clinical benefit was observed. We show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Convalescent plasma (ConvP) can contain high levels of SARS-CoV-2-neutralizing antibodies and could be regarded as an antiviral alternative for monoclonal antibodies to treat COVID-19. In SARS-CoV-2, preclinical research indicates a protective effect of human ConvP containing high levels of neutralizing antibodies when administered to hamsters prior to SARS-CoV-2 infection[14]

Objectives

Methods

Results

Conclusion