Dataset Information

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

ABSTRACT:

Background

The COVID-19 convalescent plasma (CCP) viral specific antibody levels that translate into recipient post-transfusion antibody levels sufficient to prevent disease progression is 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 post-transfusion antibody levels was established by two methods: 1) analyzing virus neutralization-equivalent anti-S-RBD IgG responses in donors or 2) receiver operating characteristic (ROC) analysis.

Results

SARS-CoV-2 anti-S-RBD IgG antibody was diluted by a factor of 21.3 into post-transfusion seronegative recipients from matched donor units. Viral specific antibody delivered approximated 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 significant association with Fisher's exact test between early and high antibodies versus all other CCP recipients (or control plasma) with antibody cutoffs established by both methods-donor virus neutralization-based cutoff: (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 corresponding to the upper 30% of all study donors reduced outpatient hospitalizations. These high antibody level plasma units, given early, should be reserved for therapeutic use.Trial registration: NCT04373460.

Funding

Defense Health Agency and others.

SUBMITTER: Park HS

PROVIDER: S-EPMC10153328 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

Park Han-Sol HS Yin Anna A Barranta Caelan C Lee John S JS Caputo Christopher A CA Sachithanandham Jaiprasath J Li Maggie M Yoon Steve S Sitaras Ioannis I Jedlicka Anne A Eby Yolanda Y Ram Malathi M Fernandez Reinaldo E RE Baker Owen R OR Shenoy Aarthi G AG Mosnaim Giselle S GS Fukuta Yuriko Y Patel Bela B Heath Sonya L SL Levine Adam C AC Meisenberg Barry R BR Spivak Emily S ES Anjan Shweta S Huaman Moises A MA Blair Janis E JE Currier Judith S JS Paxton James H JH Gerber Jonathan M JM Petrini Joann R JR Broderick Patrick B PB Rausch William W Cordisco Marie Elena ME Hammel Jean J Greenblatt Benjamin B Cluzet Valerie C VC Cruser Daniel D Oei Kevin K Abinante Matthew M Hammitt Laura L LL Sutcliffe Catherine G CG Forthal Donald N DN Zand Martin S MS Cachay Edward R ER Raval Jay S JS Kassaye Seble G SG Marshall Christi E CE Yarava Anusha A Lane Karen K McBee Nichol A NA Gawad Amy L AL Karlen Nicky N Singh Atika A Ford Daniel E DE Jabs Douglas A DA Appel Lawrence J LJ Shade David M DM Lau Bryan B Ehrhardt Stephan S Baksh Sheriza N SN Shapiro Janna R JR Ou Jiangda J Na Yu Bin YB Knoll Maria D MD Ornelas-Gatdula Elysse E Arroyo-Curras Netzahualcoyotl N Gniadek Thomas J TJ Caturegli Patrizio P Wu Jinke J Ndahiro Nelson N Betenbaugh Michael J MJ Ziman Alyssa A Hanley Daniel F DF Casadevall Arturo A Shoham Shmuel S Bloch Evan M EM Gebo Kelly A KA Tobian Aaron A R AAR Laeyendecker Oliver O Pekosz Andrew A Klein Sabra L SL Sullivan David J DJ

medRxiv : the preprint server for health sciences 20231215

<h4>Background</h4>The COVID-19 convalescent plasma (CCP) viral specific antibody levels that translate into recipient post-transfusion antibody levels sufficient to prevent disease progression is not defined.<h4>Methods</h4>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 ...[more]

PMID: 37131659

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Project description:BackgroundPolyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain.MethodsIn this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion.ResultsParticipants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized.ConclusionsIn participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).

Project description:BackgroundConvalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown.MethodsIn a retrospective study based on a U.S. national registry, we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti-SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis.ResultsOf the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti-SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32).ConclusionsAmong patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti-SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.).

Dataset Information

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

Background

Methods

Results

Conclusion

Funding

Publications

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

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