Citations 2
Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial
Park, Han-Sol , Yin, Anna , Barranta, Caelan, Caputo, Christopher , Sachithanandham, Jaiprasath , Li, Maggie , Yoon, Steve, Sitaras, Ioannis , Jedlicka, Anne , Eby, Yolanda , Ram, Malathi , Fernández, Reinaldo E. , Baker, Owen R. , Fukuta, Yuriko , Patel, Bela , Heath, Sonya L. , Spivak, Emily S , Huamán, Moisés A. , Blair, Janis E. , Gerber, Jonathan M. , Petrini, Joann, Broderick, Patrick , Rausch, William, Cordisco, Marie Elena , Hammel, Jean, Greenblatt, Benjamin, Cluzet, Valerie , Cruser, Daniel, Oei, Kevin , Abinante, Matthew, Hammitt, Laura L. , Forthal, Donald N. , Cachay, Edward R. , Marshall, Christi E., Lane, Karen , McBee, Nichol , Gawad, Amy L., Karlen, Nicky, Singh, Atika, Jabs, Douglas A. , Shade, David , Lau, Bryan , Ehrhardt, Stephan , Baksh, Sheriza , Ou, Jiangda , Na, Yu Bin , Knoll, Maria Deloria , Ornelas-Gatdula, Elysse, Gniadek, Thomas J. , Wu, Jinke, Ndahiro, Nelson , Betenbaugh, Michael J. , Ziman, Alyssa , Bloch, Evan M. , Laeyendecker, Oliver , Ziman, Alyssa , Huaman, Moises A , Laeyendecker, Oliver , Lee, John S. , Shenoy, Aarthi , Mosnaim, Giselle S , Levine, Adam C , Meisenberg, Barry R. , Anjan, Shweta , Currier, Judith S. , Paxton, James H , Sutcliffe, Catherine G , Zand, Martin S. , Raval, Jay S. , Kassaye, Seble , Yarava, Anusha , Ford, Daniel E , Appel, Lawrence J. , Shapiro, Janna R. , Arroyo‐Currás, Netzahualcóyotl , Caturegli, Patrizio , Hanley, Daniel F. , Casadevall, Arturo , Shoham, Shmuel , Gebo, Kelly A , Tobian, Aaron A.R. , Pekosz, Andrew , Klein, Sabra L , Sullivan, David
JCI Insight | April 23, 2024 | Volume: 9 | Issue: 8 | Pages: No page available
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. TRIAL REGISTRATION ClinicalTrials.gov NCT04373460. 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.
Convalescent plasma with a high level of virus-specific antibody effectively neutralizes SARS-CoV-2 variants of concern
Li, Maggie , Beck, Evan J. , Laeyendecker, Oliver , Eby, Yolanda , Wouters, Camille, Chiklis, Gregory R., Block, William , McKie, Robert O., Joyner, Michael J. , Wiltshire, Timothy D. , Dietz, Allan B. , Gniadek, Thomas J. , Shapiro, Arell, Yarava, Anusha , Lane, Karen , Bloch, Evan M. , Cachay, Edward R. , Huamán, Moisés A. , Fukuta, Yuriko , Patel, Bela , Heath, Sonya L. , Gerber, Jonathan M. , Sullivan, David , Wiltshire, Timothy D , Dietz, Allan B , Hanley, Daniel F , Bloch, Evan M , Shoham, Shmuel , Cachay, Edward R , Huaman, Moises A , Levine, Adam C , Paxton, James H , Gerber, Jonathan M , Gebo, Kelly A , Casadevall, Arturo , Sullivan, David J , Joyner, Michael J , Laeyendecker, Oliver , Tobian, Aaron A.R. , Caturegli, Patrizio , Block, William, Hanley, Daniel F. , Shoham, Shmuel , Meisenberg, Barry R. , Anjan, Shweta , Casadevall, Arturo , Pekosz, Andrew
Blood Advances | April 20, 2022 | Volume: 6 | Issue: 12 | Pages: 3678-3683
10.1182/bloodadvances.2022007410
Abstract The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants severely limits available effective monoclonal antibody therapies. Effective drugs are also supply limited. COVID-19 convalescent plasma (CCP) qualified for high antibody levels effectively reduces immunocompetent outpatient hospitalization. The Food and Drug Administration currently allows outpatient CCP for the immunosuppressed. Viral-specific antibody levels in CCP can range 10- to 100-fold between donors, unlike the uniform viral-specific monoclonal antibody dosing. Limited data are available on the efficacy of polyclonal CCP to neutralize variants. We examined 108 pre-δ/pre-ο donor units obtained before March 2021, 20 post-δ COVID-19/postvaccination units, and 1 pre-δ/pre-ο hyperimmunoglobulin preparation for variant-specific virus (vaccine-related isolate [WA-1], δ, and ο) neutralization correlated to Euroimmun S1 immunoglobulin G antibody levels. We observed a two- to fourfold and 20- to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to δ or ο, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-δ COVID-19/postvaccination units and the hyperimmunoglobulin effectively neutralized all 3 variants. High-titer CCP neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants.