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

J Intern Med. 2021 Apr;289(4):559-573. doi: 10.1111/joim.13185. Epub 2020 Nov 3.

Abstract

Background: Convalescent plasma therapy for COVID-19 relies on 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: Donor antibody titres ranged from 0 to 1 : 3892 (anti-receptor binding domain (RBD)) and 0 to 1 : 3289 (anti-spike). Higher anti-RBD and anti-spike titres 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). In pairwise comparison amongst ABO blood types, AB donors had higher anti-RBD and anti-spike than O donors (P < 0.05). No toxicity was associated with plasma transfusion. Non-ECMO recipient anti-RBD antibody titre increased on average 31% per day during the first three days post-transfusion (P = 0.01) and anti-spike antibody titre by 40.3% (P = 0.02).

Conclusion: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titre to COVID-19. Despite variability in donor titre, 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 amongst COVID-19-infected patients is needed.

Keywords: COVID-19; antibody titre; convalescent plasma.

Publication types

  • Clinical Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood*
  • Antibody Formation / immunology*
  • COVID-19 / epidemiology
  • COVID-19 / immunology
  • COVID-19 / physiopathology
  • COVID-19 / therapy*
  • COVID-19 Serological Testing* / methods
  • COVID-19 Serological Testing* / statistics & numerical data
  • Female
  • Humans
  • Immunization, Passive / methods
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • SARS-CoV-2* / immunology
  • SARS-CoV-2* / isolation & purification
  • Symptom Assessment* / methods
  • Symptom Assessment* / statistics & numerical data
  • Treatment Outcome
  • United States

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G

Supplementary concepts

  • COVID-19 serotherapy