Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 132, Issue 12, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI158190
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Funding
- Innovation Pool project by the University Hospital Zurich
- Swiss Red Cross Gluckskette Corona Funding
- Pandemiefonds of the UZH Foundation
- Clinical Research Priority Program Comprehensive Genomic Pathogen Detection of the University of Zurich
- Promedica Foundation [14851M]
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This study provides preliminary evidence that treatment with convalescent plasma therapy, particularly with highly neutralizing plasma, is associated with faster clearance of the SARS-CoV-2 virus in hospitalized COVID-19 patients.
BACKGROUND: Neutralizing 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 elucidate. METHODS: We 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. RESULTS: In 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). CONCLUSION: Our 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 REGISTRATION: ClinicalTrials.gov NCT04869072. FUNDING: This study was funded via an Innovation Pool project by the University Hospital Zurich; the Swiss Red Cross Gluckskette Corona Funding; Pandemiefonds of the UZH Foundation; and the Clinical Research Priority Program Comprehensive Genomic Pathogen Detection of the University of Zurich.
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