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

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.

Fig. 1

Recipient hospital course. Recipient clinical course before and after plasma transfusion (day 0). Number of days symptomatic prior to admission (grey) and recipient location in the intensive care unit (ICU, red), hospital floor (yellow) and home (green) shown by day of plasma transfusion. Positive SARS‐CoV‐2 NP swab PCR test indicated by black triangle and negative test indicated by white triangle. Repeat plasma dosing indicated by blue circle. Respiratory support at time of plasma transfusion indicated by left column (ECMO, extracorporeal membrane oxygenation; vent, mechanical ventilation; nasal cannula; room air).

Fig. 2

Recipient clinical and laboratory parameters after plasma transfusion. (a) Maximum daily temperature (T _max, c); (b) Type of respiratory support required (ECMO, extracorporeal membranous oxygenation; Vent, mechanically ventilated; HFNC, high‐flow nasal cannula; L, number of litres of oxygen on nasal cannula); (c) Sequential Organ Failure Assessment (SOFA) score for recipients on mechanical ventilation or ECMO; (d) Inflammatory marker C‐reactive protein (CRP). Data for patients on ECMO are in red.

Fig. 3

Recipient serology after plasma transfusion. Reciprocal donor plasma anti‐RBD (red circle) and anti‐spike (blue circle) antibody titre are plotted on the y‐axis. Dotted line at 1:50 represents the limits of antibody detection. Reciprocal recipient anti‐RBD (red line) and anti‐spike (blue line) antibody titre are plotted on day 0 prior to transfusion and on days 1, 3, 7 and 14 post‐transfusion.

Fig. 4

Antibody response curve in plasma recipients. Log‐transformed rate of antibody titre change of anti‐RBD and anti‐spike antibodies in the non‐ECMO (n = 8) and ECMO (n = 2) recipients were fitted in a mixed effects piecewise linear regression model.