Clinical predictors of donor antibody titer and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial
Authors: Madariaga Maria Lucia L. , Guthmiller Jenna J. , Schrantz Stephen , Jansen Maud O. , Christensen Chancey , Kumar Madan , Prochaska Micah , Wool Geoffrey , Durkin-Celauro Amy , Oh Won Hee , Trockman Laura , Vigneswaran Janani , Keskey Robert , Shaw Dustin G. , Dugan Haley , Zheng Nai-Ying , Cobb Mari , Utset Henry , Wang Jiaolong , Stovicek Olivia , Bethel Cindy , Matushek Scott , Giurcanu Mihai , Beavis Kathleen G. , Sabato Diego di , Meltzer David , Ferguson Mark K. , Kress John P. , Shanmugarajah Kumaran , Matthews Jeffrey B. , Fung John F. , Wilson Patrick C. , Alverdy John C. , Donington Jessica S. 
Published: June 2020

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.

Findings

Mean symptom duration of plasma donors was 11.9±5.9 days 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).

Interpretation

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.

Trial Registration

NCT04340050

Funding

Department of Surgery University of Chicago, National Institute of Allergy and Infectious Diseases (NIAID) Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051