Clinical predictors of donor antibody titer and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial

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Author Name

Maria Lucia L Madariaga

Published 1 Project

Infectious Diseases

Stephen Schrantz

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Infectious Diseases

Maud Jansen

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Immunology Infectious Diseases

Chancey Christenson

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Infectious Diseases

Madan Kumar

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Infectious Diseases

Micah Prochaska

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Infectious Diseases

Geoffrey Wool

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Infectious Diseases

Amy Durkin

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Won Hee Oh

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Laura Trockman

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Janani Vigneswaran

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Robert Keskey

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Dustin G Shaw

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Nai Zheng

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Mari Cobb

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Infectious Diseases

Henry Utset

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Immunology Infectious Diseases

Jiaolong Wang

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Immunology Infectious Diseases

Cindy Bethel

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Infectious Diseases

Scott Matushek

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Infectious Diseases

Mihai Giurcanu

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Kathleen Beavis

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Diego diSabato

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David Meltzer

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Mark Ferguson

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John P Kress

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Kumaran Shanmugarajah

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Immunology Infectious Diseases

Jeffrey Matthews

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Infectious Diseases

John Fung

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Infectious Diseases

John C Alverdy

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Infectious Diseases

Jessica Donington

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Infectious Diseases

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Background: Convalescent plasma therapy for COVID-19 relies on the transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. Methods: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. Results: Mean symptom duration of plasma donors was 11.9 and 7.8% (8/103) had been hospitalized. Antibody titers ranged from 0 to 1:3,892 (anti-receptor binding domain (RBD)) and 0 to 1:3,289 (anti-spike). Multivariable analysis demonstrated that higher anti-RBD and anti-spike titer were associated with increased age, hospitalization for COVID-19, fever, and absence of myalgia (all p<0.05). Fatigue was significantly associated with anti-RBD (p=0.03) but not anti-spike antibody titer (p=0.11). In pairwise comparison among ABO blood types, AB donors had higher anti-RBD titer than O negative donors (p=0.048) and higher anti-spike titer than O negative (p=0.015) or O positive (p=0.037) donors. Eight of the ten recipients were discharged, one remains on ECMO and one died on ECMO. No toxicity was associated with plasma transfusion. After excluding two ECMO patients and adjusting for donor antibody titer, recipient anti-RBD antibody titer increased on average 31% per day during the first three days post-transfusion (p=0.01) and anti-spike antibody titer by 40.3% (p=0.02). Conclusion: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titer to COVID-19. Despite variability in donor titer, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion among COVID-19 patients is needed to determine the clinical efficacy of this therapy.

Infectious Diseases
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