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COVID-19 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-analysis of Individual Participant Data From Five Randomized Trials

Department of Emergency Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. Department of Medicine - Infectious Disease, Baylor College of Medicine, Houston, Texas, USA. Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Division of Brain Injury Outcomes, Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA. Department of Hematology - Oncology, Anne Arundel Medical Center, Annapolis, Maryland, USA. Division of Critical Care Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, Texas, USA. Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, Michigan, USA. Department of Internal Medicine, Section of Infectious Diseases and department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Department of Haematology, Leiden University Medical Centre, Leiden, The Netherlands and; CCTR, Sanquin Blood Supply, Amsterdam, The Netherlands. Fight Infectious Diseases Foundation, Badalona, Spain; Infectious Diseases Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. Lihir Medical Centre, International SOS, Lihir Island, Papua New Guinea. ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain. Medical University of South Carolina, Charleston, SCUSA. University of Michigan, Ann Arbor, MIUSA. Vitalant Research Institute, Denver, CO; University of Colorado School of Medicine, Aurora, CO USA. University of Pittsburgh, Pittsburgh, PAUSA. Fundación INFANT, Buenos Aires, Argentina. Vanderbilt University, Nashville, TN, USA. Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023
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PICO Summary

Population

Adult COVID-19 outpatients (5 studies, n= 2,620).

Intervention

Intravenous COVID-19 convalescent plasma (CCP) transfusion (n= 1,305).

Comparison

Non-convalescent plasma or normal saline (n= 1,315).

Outcome

The virus neutralizing antibody dilutional titre levels ranged from 8 to 14,580 in diverse assays. 160 (12.2%) of 1,315 control patients were hospitalized, versus 111 (8.5%) of 1,305 COVID-19 convalescent plasma treated patients, yielding a 3.7% (95% CI: 1.3% - 6.0%) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titre with a 7.6% absolute risk reduction (95% CI: 4.0% - 11.1%) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment > 5 days after symptom onset or in those receiving COVID-19 convalescent plasma with antibody titres below the median titre.
Abstract
BACKGROUND Outpatient monoclonal antibodies are no longer effective and antiviral treatments for COVID-19 disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma is promising, clinical trials among outpatients have shown mixed results. METHODS We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching MEDLINE, Embase, MedRxiv, World Health Organization, Cochrane Library, and Web of Science from January 2020 to September 2022. RESULTS Five included studies from four countries enrolled and transfused 2,620 adult patients. Comorbidities were present in 1,795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14,580 in diverse assays. 160 (12.2%) of 1315 control patients were hospitalized, versus 111 (8.5%) of 1305 COVID-19 convalescent plasma treated patients, yielding a 3.7% (95%CI: 1.3%-6.0%; p=.001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95%CI: 4.0%-11.1%; p=.0001) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment > 5 days after symptom onset or in those receiving COVID-19 convalescent plasma with antibody titers below the median titer. CONCLUSIONS Among outpatients with COVID-19, treatment with COVID-19 convalescent plasma reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher.
Study details
Study Design : Systematic Review
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine