Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial
Authors: Park Han-Sol , Yin Anna , Barranta Caelan , Lee John S. , Caputo Christopher A. , Sachithanandham Jaiprasath , Li Maggie , Yoon Steve , Sitaras Ioannis , Jedlicka Anne , Eby Yolanda , Ram Malathi , Fernandez Reinaldo E. , Baker Owen R. , Shenoy Aarthi G. , Mosnaim Giselle S. , Fukuta Yuriko , Patel Bela , Heath Sonya L. , Levine Adam C. , Meisenberg Barry R. , Spivak Emily S. , Anjan Shweta , Huaman Moises A. , Blair Janis E. , Currier Judith S. , Paxton James H. , Gerber Jonathan M. , Petrini Joann R. , Broderick Patrick B. , Rausch William , Cordisco Marie Elena , Hammel Jean , Greenblatt Benjamin , Cluzet Valerie C. , Cruser Daniel , Oei Kevin , Abinante Matthew , Hammitt Laura L. , Sutcliffe Catherine G. , Forthal Donald N. , Zand Martin S. , Cachay Edward R. , Raval Jay S. , Kassaye Seble G. , Marshall Christi E. , Yarava Anusha , Lane Karen , McBee Nichol A. , Gawad Amy L. , Karlen Nicky , Singh Atika , Ford Daniel E. , Jabs Douglas A. , Appel Lawrence J. , Shade David M. , Lau Bryan , Ehrhardt Stephan , Baksh Sheriza N. , Shapiro Janna R. , Ou Jiangda , Na Yu Bin , Knoll Maria D. , Ornelas-Gatdula Elysse , Arroyo-Curras Netzahualcoyotl , Gniadek Thomas J. , Caturegli Patrizio , Wu Jinke , Ndahiro Nelson , Betenbaugh Michael J. , Ziman Alyssa , Hanley Daniel F. , Casadevall Arturo , Shoham Shmuel , Bloch Evan M. , Gebo Kelly A. , Tobian Aaron A.R. , Laeyendecker Oliver , Pekosz Andrew , Klein Sabra L. , Sullivan David J. 
Published: April 2023

ABSTRACTBACKGROUNDThe 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.METHODSThis 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.RESULTSSARS-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.CONCLUSIONIn 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:NCT04373460FUNDINGDefense Health Agency and others.