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Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response.
Marconato, Maddalena; Abela, Irene A; Hauser, Anthony; Schwarzmüller, Magdalena; Katzensteiner, Rheliana; Braun, Dominique L; Epp, Selina; Audigé, Annette; Weber, Jacqueline; Rusert, Peter; Schindler, Eméry; Pasin, Chloé; West, Emily; Böni, Jürg; Kufner, Verena; Huber, Michael; Zaheri, Maryam; Schmutz, Stefan; Frey, Beat M; Kouyos, Roger D; Günthard, Huldrych F; Manz, Markus G; Trkola, Alexandra.
  • Marconato M; Department of Medical Oncology and Haematology; University Hospital Zurich and University of Zurich; Comprehensive Cancer Center Zurich; Switzerland.
  • Abela IA; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
  • Hauser A; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Schwarzmüller M; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
  • Katzensteiner R; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Braun DL; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
  • Epp S; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
  • Audigé A; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Weber J; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Rusert P; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Schindler E; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Pasin C; Blood Transfusion Service Zurich, Swiss Red Cross, Zurich, Switzerland.
  • West E; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
  • Böni J; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Kufner V; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
  • Huber M; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Zaheri M; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Schmutz S; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Frey BM; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Kouyos RD; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Günthard HF; Blood Transfusion Service Zurich, Swiss Red Cross, Zurich, Switzerland.
  • Manz MG; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
  • Trkola A; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
J Clin Invest ; 132(12)2022 06 15.
Article in English | MEDLINE | ID: covidwho-2053515
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Humans Language: English Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Humans Language: English Year: 2022 Document Type: Article