Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Fight AIDS and Infectious Diseases Foundation, Badalona, Spain. ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain. Department of Internal Medicine, Section of Infectious Diseases and department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Hospital Universitari Germans Trias i Pujol, Badalona, Spain. Facultat de Medicina-Universitat de Barcelona, Barcelona, Spain. Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands. Department of Biostatistics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Department of Biomedical Data Sciences, Section of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands. Department of Infectious Diseases and Acute Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands. Unit of Transfusion Medicine, Sanquin Blood Supply, Amsterdam, The Netherlands. Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands. Hospital Universitari Parc Taulí I3PT, Sabadell, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Bioclever-CRO, Barcelona, Spain. Emergency Department, Bellvitge University Hospital, L'Hospitalet de LLobregat, Barcelona, Spain. Clinical Research Support Unit (HUB-IDIBELL: Bellvitge University Hospital & Bellvitge Biomedical Research Institute), Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain. Pharmacology Unit, Department of Pathology and Experimental Therapeutics, School of Medicine and 33 Health Sciences, IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain. Unitat de Suport a la Recerca de la Catalunya Central, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina, Sant Fruitós de Bages, Spain. Health Promotion in Rural Areas Research Group, Gerència Territorial de la Catalunya Central, Institut Català de la Salut, Sant Fruitós de Bages, Spain. Universitat de Vic-Universitat Central de Catalunya (UVIC-UCC), Vic, Spain. Salut Catalunya Central, Hospital de Berga, Berga, Spain. Blood Bank Department-Banc de Sang i Teixits (BST), Barcelona, Spain. IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain. Metropolitana Nord Laboratory, Institut Català de la Salut, Badalona, Spain. Gerència Territorial Metropolitana Nord, Institut Català de la Salut, Barcelona, Spain. Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique. Pg. Lluís Companys 23, ICREA, Barcelona, Spain. Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues, Spain. Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Department of Population Health, NYU Grossman School of Medicine, New York, NY, USA. Department of Haematology, Leiden University Medical Centre, Leiden, The Netherlands. CCTR, Sanquin Blood Supply, Amsterdam, The Netherlands. Lihir Medical Centre-InternationalSOS, Lihir Island, Papua New Guinea. Department of Internal Medicine, Section of Infectious Diseases and department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. b.rijnders@erasmusmc.nl.

Nature communications. 2022;13(1):2583
PICO Summary

Population

COVID-19 outpatients enrolled in two multicenter trials: COnV-ert and CoV-Early (n= 797).

Intervention

Convalescent plasma (n= 390).

Comparison

Placebo (n= 392).

Outcome

Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of convalescent plasma for improved disease severity scale was 0.936; OR for hospitalization or death was 0.919. The convalescent plasma effect on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658). Convalescent plasma did not decrease the time to full symptom resolution.
Abstract
Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when <20% of recruitment target was achieved. A Bayesian-adaptive individual patient data meta-analysis was implemented. Outpatients aged ≥50 years and symptomatic for ≤7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution. TRIAL REGISTRATION Clinicaltrials.gov NCT04621123 and NCT04589949. REGISTRATION NCT04621123 and NCT04589949 on https://www. CLINICALTRIALS gov.
Study details
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine