Abstract
BACKGROUNDNeutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The manner in which human infections respond to therapeutic SARS-CoV-2 antibodies, including convalescent plasma therapy, remains to be fully elucidated.METHODSWe conducted a proof-of-principle study of convalescent plasma therapy based on a phase I trial in 30 hospitalized COVID-19 patients with a median interval between onset of symptoms and first transfusion of 9 days (IQR, 7-11.8 days). Comprehensive longitudinal monitoring of the virological, serological, and disease status of recipients allowed deciphering of parameters on which plasma therapy efficacy depends.RESULTSIn this trial, convalescent plasma therapy was safe as evidenced by the absence of transfusion-related adverse events and low mortality (3.3%). Treatment with highly neutralizing plasma was significantly associated with faster virus clearance, as demonstrated by Kaplan-Meier analysis (P = 0.034) and confirmed in a parametric survival model including viral load and comorbidity (adjusted hazard ratio, 3.0; 95% CI, 1.1-8.1; P = 0.026). The onset of endogenous neutralization affected viral clearance, but even after adjustment for their pretransfusion endogenous neutralization status, recipients benefitted from plasma therapy with high neutralizing antibodies (hazard ratio, 3.5; 95% CI, 1.1-11; P = 0.034).CONCLUSIONOur data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia before and after onset of the endogenous neutralizing response, and point beyond antibody-based interventions to critical laboratory parameters for improved evaluation of current and future SARS-CoV-2 therapies.TRIAL REGISTRATIONClinicalTrials.gov NCT04869072 .FUNDINGThis study was funded via an Innovation Pool project by the University Hospital Zurich; the Swiss Red Cross Glückskette Corona Funding; Pandemiefonds of the UZH Foundation; and the Clinical Research Priority Program “Comprehensive Genomic Pathogen Detection” of the University of Zurich.
Keywords: Adaptive immunity; COVID-19; Immunotherapy; Therapeutics.
【저자키워드】 COVID-19, Adaptive immunity, Therapeutics, Immunotherapy, 【초록키워드】 neutralizing antibody, SARS-CoV-2, Adaptive immunity, Efficacy, therapy, Mortality, Trial, Phase I, antibody, Therapeutics, neutralization, Immunotherapy, Comorbidity, Intervention, SARS-CoV-2 vaccines, plasma therapy, viral clearance, Clinical research, adverse events, SARS-CoV-2 antibodies, survival, Viral, Convalescent plasma therapy, Viremia, Corona, Viral load, therapeutic, Program, plasma, Neutralizing, university, serological, Critical, hospitalized COVID-19 patient, Innovation, Safe, Virological, 95% CI, adjusted hazard ratio, principle, recipients, hazard ratio, virus clearance, pool, priority, human infection, disease status, human infections, median interval, recipient, Kaplan-Meier analysis, clearance, parameter, laboratory parameter, transfusion-related adverse events, Comprehensive, affected, significantly, conducted, onset of symptom, absence, faster, demonstrated, evidenced, respond, IQR, Red, transfusion-related adverse event, University of Zurich, 【제목키워드】 convalescent plasma, Antibody Response, individual, SARS-CoV-2 clearance, promote,