Abstract

COVID-19 is an ongoing pandemic with high morbidity and mortality. Despite meticulous research, only dexamethasone has shown consistent mortality reduction. Convalescent plasma (CP) infusion might also develop into a safe and effective treatment modality on the basis of recent studies and meta-analyses; however, little is known regarding the kinetics of antibodies in CP recipients. To evaluate the kinetics, we followed 31 CP recipients longitudinally enrolled at a median of 3 days post symptom onset for changes in binding and neutralizing antibody titers and viral loads. Antibodies against the complete trimeric Spike protein and the receptor-binding domain (Spike-RBD), as well as against the complete Nucleocapsid protein and the RNA binding domain (N-RBD) were determined at baseline and weekly following CP infusion. Neutralizing antibody (pseudotype NAb) titers were determined at the same time points. Viral loads were determined semi-quantitatively by SARS-CoV-2 PCR. Patients with low humoral responses at entry showed a robust increase of antibodies to all SARS-CoV-2 proteins and Nab, reaching peak levels within 2 weeks. The rapid increase in binding and neutralizing antibodies was paralleled by a concomitant clearance of the virus within the same timeframe. Patients with high humoral responses at entry demonstrated low or no further increases; however, virus clearance followed the same trajectory as in patients with low antibody response at baseline. Together, the sequential immunological and virological analysis of this well-defined cohort of patients early in infection shows the presence of high levels of binding and neutralizing antibodies and potent clearance of the virus.

Highlights

  • Coronavirus disease 19 (COVID-19) is an infectious disease caused by the newly emerged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

  • We evaluated anti-SARS-CoV-2 antibody and viral load kinetics in a well-studied subcohort of 31 patients with severe COVID-19 who were treated with convalescent plasma

  • We showed that patients with undetectable neutralizing antibodies at baseline showed a sharp increase in all anti-SARSCoV-2-binding antibodies following convalescent plasma (CP) infusion, reaching peak levels within two weeks post-CP

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Summary

Introduction

Coronavirus disease 19 (COVID-19) is an infectious disease caused by the newly emerged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The US Food and Drug Administration (FDA) granted Emergency Use Authorization for two neutralizing antibody cocktails (casirivimab/imdevimab and bamlanivimab/etesevimab), as well as monotherapy with bamlanivimab for treatment of ambulatory patients who have a high risk of progressing to severe disease [6]. Individual randomized control trials on the efficacy of convalescent plasma (CP) have shown negative results [7,8,9,10,11,12,13,14,15,16,17]; two recent meta-analyses have demonstrated the efficacy of convalescent plasma (CP) in mortality reduction of patients with severe COVID-19, to the results of several matchedcontrol trials [18,19]. A survival benefit of patients treated with CP was recently shown by our group in a matched propensity score analysis of 59 patients [20]

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