Publication Date
3-14-2024
Journal
JCI Insight
DOI
10.1172/jci.insight.178460
PMID
38483534
PMCID
PMC11141865
PubMedCentral® Posted Date
3-14-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, COVID-19, COVID-19 Serotherapy, Antibodies, Viral, Immunization, Passive, Hospitalization, SARS-CoV-2, Male, Female, Middle Aged, Adult, Immunoglobulin G, Antibodies, Neutralizing, Double-Blind Method, Aged, Blood Donors, Outpatients, Immunoglobulins, Immunotherapy
Abstract
BACKGROUND
COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.
METHODS
This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization–equivalent anti–Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.
RESULTS
SARS-CoV-2 anti–S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).
CONCLUSION In unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors’ antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.
FUNDING Department of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.
Graphical Abstract
Included in
Diseases Commons, Immunotherapy Commons, Infectious Disease Commons, Medical Sciences Commons
Comments
Associated Data
TRIAL REGISTRATION ClinicalTrials.gov NCT04373460.