COVID-19 inpatient convalescent plasma: an open-label randomized controlled trial
Bégin, P., Callum, J., Jamula, E. et al. Recovery plasma in hospitalized patients with COVID-19: an open-label randomized controlled trial. Nat Med (2021). https://doi.org/10.1038/s41591-021-01488-2
Commentary
Recovery plasma is one of the treatment options for COVID-19, but its efficacy is unknown. Most randomized controlled trials to date have shown negative results, but uncontrolled trials suggest that antibody content may affect patient outcomes.
An open-label, randomized, controlled trial of convalescent plasma was conducted in adults with COVID-19 who were receiving oxygen within 12 days of the onset of respiratory symptoms.
Patients were assigned 2:1 to 500 ml of convalescent plasma, standard of care, and the composite primary outcome was intubation or death by 30 days.
An exploratory analysis of the effect of convalescent plasma antibodies on primary outcome was assessed by logistic regression, and the trial was terminated at 78% of planned enrollment after the futility cessation criteria were met.
A total of 940 patients were randomized to the study, and 921 patients were included in the ITT analysis.
Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma group and 86/307 (28.0%) patients in the standard care group, with a relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94 -1.43, P = .18). In the recovery phase, the plasma group had a higher RR of 1.16.
Patients in the convalescent plasma group had more severe adverse events (33.4% vs. 26.4%; RR = 1.27, 95% CI 1.02-1.57, P = .034).
Antibody content significantly modulated the therapeutic effect of convalescent plasma. Multivariate analysis showed that for each standardized logarithmic increase in neutralization, or antibody-dependent cytotoxicity, there was an independent decrease in the potential adverse effects of plasma (odds ratio
On the other hand, IgG against complete transmembrane spike proteins increased it (OR = 1.53, 95% CI 1.14-2.05).
Recovery plasma did not reduce the risk of intubation or death at 30 days in hospitalized patients with COVID-19, and transfusion of recovery plasma with an adverse antibody profile may be associated with poorer clinical outcomes compared with standard care.
