Markers of Polyfunctional SARS-CoV-2 Antibodies in Convalescent Plasma.
Harini Natarajan,Andrew R. Crowley,Savannah E. Butler,Shiwei Xu,Joshua A. Weiner,Evan M. Bloch,Kirsten Littlefield,Wendy Wieland-Alter,Ruth I Connor,Peter F. Wright,Sarah E. Benner,Tania S. Bonny,Oliver Laeyendecker,Oliver Laeyendecker,David J. Sullivan,Shmuel Shoham,Thomas C. Quinn,Thomas C. Quinn,H. Benjamin Larman,Arturo Casadevall,Andrew Pekosz,Andrew D. Redd,Andrew D. Redd,Aaron A.R. Tobian,Margaret E. Ackerman +24 more
TLDR
In this paper, a survey of the diversity of antibody-mediated antiviral functions associated with convalescent plasma was used to define plasma samples with broad activity profiles, and these polyfunctional plasma samples could be reliably identified in multiple cohorts by multiplex assay, presenting a widely deployable screening test for plasma selection and investigation of vaccine-elicited responses.Abstract:
Convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), but the antibody characteristics that contribute to efficacy remain poorly understood. This study analyzed plasma samples from 126 eligible convalescent blood donors in addition to 15 naive individuals, as well as an additional 20 convalescent individuals as a validation cohort. Multiplexed Fc Array binding assays and functional antibody response assays were utilized to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody composition and activity. Donor convalescent plasma samples contained a range of antibody cell- and complement-mediated effector functions, indicating the diverse antiviral activity of humoral responses observed among recovered individuals. In addition to viral neutralization, convalescent plasma samples contained antibodies capable of mediating such Fc-dependent functions as complement activation, phagocytosis, and antibody-dependent cellular cytotoxicity against SARS-CoV-2. Plasma samples from a fraction of eligible donors exhibited high activity across all activities evaluated. These polyfunctional plasma samples could be identified with high accuracy with even single Fc Array features, whose correlation with polyfunctional activity was confirmed in the validation cohort. Collectively, these results expand understanding of the diversity of antibody-mediated antiviral functions associated with convalescent plasma, and the polyfunctional antiviral functions suggest that it could retain activity even when its neutralizing capacity is reduced by mutations in variant SARS-CoV-2.IMPORTANCE Convalescent plasma has been deployed globally as a treatment for COVID-19, but efficacy has been mixed. Better understanding of the antibody characteristics that may contribute to its antiviral effects is important for this intervention as well as offer insights into correlates of vaccine-mediated protection. Here, a survey of convalescent plasma activities, including antibody neutralization and diverse effector functions, was used to define plasma samples with broad activity profiles. These polyfunctional plasma samples could be reliably identified in multiple cohorts by multiplex assay, presenting a widely deployable screening test for plasma selection and investigation of vaccine-elicited responses.read more
Citations
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Early Outpatient Treatment for Covid-19 with Convalescent Plasma
TL;DR: In this article , the authors 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.
Journal ArticleDOI
Correlates of protection against SARS‐CoV‐2 infection and COVID‐19 disease
TL;DR: Antibodies against epitopes in S1 give the most accurate CoP against infection by the SARS‐CoV‐2 coronavirus, and the role of cellular responses can be discerned with respect to CD4+ T cells and their augmentation of antibodies, and with regard to control of viral replication.
Journal ArticleDOI
Results of the CAPSID randomized trial for high-dose convalescent plasma in patients with severe COVID-19.
Sixten Körper,Manfred Weiss,Daniel Zickler,Thomas Wiesmann,Kai Zacharowski,Victor M. Corman,Beate Grüner,Lucas Ernst,Peter M. Spieth,Philipp M. Lepper,Martin Bentz,Sebastian Zinn,Gregor Paul,Johannes Kalbhenn,Matthias M Dollinger,Peter Rosenberger,Thomas Kirschning,Thomas Thiele,Thomas Appl,Benjamin Mayer,Michael Schmidt,Christian Drosten,Hinnerk Wulf,Jan Kruse,Bettina Jungwirth,Erhard Seifried,Hubert Schrezenmeier +26 more
TL;DR: In this article, the authors evaluated the efficacy of neutralizing antibody containing high-dose COVID-19 convalescent plasma (CCP) in hospitalized adults requiring respiratory support or intensive care treatment.
Journal ArticleDOI
COVID-19 Convalescent Plasma and Clinical Trials: Understanding Conflicting Outcomes
Daniele Focosi,Massimo Franchini,Liise Anne Pirofski,Thierry Burnouf,Nigel Paneth,Michael J. Joyner,Arturo Casadevall +6 more
TL;DR: A review of 30 available RCTs demonstrated that signals of efficacy were more likely if the CCP neutralizing titer was higher than 160 and the time to randomization was less than 9 days, demonstrating confusion for both clinicians and patients about the appropriate use of CCP.
Journal ArticleDOI
Decay of Fc-dependent antibody functions after mild to moderate COVID-19.
Wen Shi Lee,Kevin J. Selva,Samantha K Davis,Bruce D. Wines,Bruce D. Wines,Bruce D. Wines,Arnold Reynaldi,Robyn Esterbauer,Hannah G. Kelly,Hannah G. Kelly,Ebene R. Haycroft,Hyon-Xhi Tan,Jennifer A Juno,Adam K. Wheatley,Adam K. Wheatley,P. Mark Hogarth,P. Mark Hogarth,P. Mark Hogarth,Deborah Cromer,Miles P. Davenport,Amy W. Chung,Stephen J. Kent,Stephen J. Kent,Stephen J. Kent +23 more
TL;DR: In this paper, the authors developed assays to measure Fc-dependent antibody functions against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-expressing cells in serial samples from subjects primarily with mild-moderate COVID-19 up to 149 days post-infection.
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