Convalescent plasma does not reduce the risk of intubation or death for COVID-19 patients, and may actually lead to more adverse events, a new study has found.

The Canadian-led international research team also found that patients receiving convalescent plasma experienced significantly more serious adverse events than those receiving standard care. The majority of those events included an increased need for oxygen and worsening respiratory failure. However, the rate of fatal incidents was not significantly different from the control group of patients who did not receive the blood.

Part of the reason plasma struck out as a potentially helpful treatment may have been that the researchers found that it had highly variable donor antibody content due to the highly variable immunological response to the virus. Different antibody profiles in the convalescent plasma were observed to significantly impact whether or not patients experienced intubation or death. Unfavorable antibody profiles were associated with a higher risk of intubation or death.

“One hypothesis is that those dysfunctional antibodies could compete with the patient’s own antibodies and could disrupt the mounting immune response,” said co-principal investigator Philippe Bégin, M.D., Ph.D., associate professor at the University of Montréal. “This phenomenon has been observed previously in animal models and in human studies of HIV vaccines.”

The clinical trial, called CONCOR-1, stopped enrolment early in January after its independent data safety monitoring committee recommended the study was unlikely to demonstrate a benefit of convalescent plasma even if more patients were enrolled. The trial included 940 patients at 72 hospitals in Canada, the United States, and Brazil. The U.S. team was coordinated by Weill Cornell Medicine.

Results of the study were published in the journal Nature Medicine Thursday.