Coronavirus Disease 2019 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-Analysis of Individual Participant Data From 5 Randomized Trials

Authors

Adam C Levine
Yuriko Fukuta
Moises A Huaman
Jiangda Ou
Barry R Meisenberg
Bela Patel
James H Paxton
Daniel F Hanley
Bart J A Rijnders
Arvind Gharbharan
Casper Rokx
Jaap Jan Zwaginga
Andrea Alemany
Oriol Mitjà
Dan Ouchi
Pere Millat-Martinez
Valerie Durkalski-Mauldin
Frederick K Korley
Larry J Dumont
Clifton W Callaway
Romina Libster
Gonzalo Perez Marc
Diego Wappner
Ignacio Esteban
Fernando Polack
David J Sullivan

Publication Date

6-16-2023

Journal

Clinical Infectious Diseases

DOI

10.1093/cid/ciad088

PMID

36809473

PMCID

PMC10273382

PubMedCentral® Posted Date

2-21-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Adult, Humans, COVID-19, Outpatients, SARS-CoV-2, COVID-19 Serotherapy, Randomized Controlled Trials as Topic, Hospitalization, SARS-CoV-2, COVID-19 convalescent plasma, hospitalization, therapy, COVID-19

Abstract

BACKGROUND: Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma (CCP) 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 COVID-19 Research Database, Cochrane Library, and Web of Science from January 2020 to September 2022.

RESULTS: Five included studies from 4 countries enrolled and transfused 2620 adult patients. Comorbidities were present in 1795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14 580 in diverse assays. One hundred sixty of 1315 (12.2%) control patients were hospitalized, versus 111 of 1305 (8.5%) CCP-treated patients, yielding a 3.7% (95% confidence interval [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 CCP with antibody titers below the median titer.

CONCLUSIONS: Among outpatients with COVID-19, treatment with CCP 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.