Convalescent plasma fails to improve outcomes in severe COVID-19

Infusion of convalescent plasma is no better than placebo in terms of clinical status or mortality in patients with severe COVID-19 pneumonia, according to results of a randomised trial conducted in Argentina.

“Convalescent plasma has been used for the treatment of infectious diseases for more than a century, under the assumption that passive immunisation can ‘jump start’ the immune system to control the evolution of the disease until a specific immune response is established in the infected person,” wrote study authors led by Ventura Simonovich, of the Clinical Pharmacology Section at Hospital Italiano de Buenos Aires.

There has been substantial interest in the use of convalescent plasma for COVID-19. In a controversial move in the US in August, the FDA issued an Emergency Use Authorisation, despite a lack of randomised trial evidence.

The new trial, published in the NEJM, randomised 333 hospitalised patients to receive either convalescent plasma or placebo.

After 30 days, there were no differences between the groups with regard to their clinical status, which was measured on a six-point scale ranging from total recovery to death (P = .396). Similar proportions of patients required ventilatory support, supplemental oxygen, and were discharged either with or without a full return to baseline function.

The overall mortality rate was 10.96% among those who received plasma, compared with 11.43% in those who received placebo.

The study did find that total SARS-CoV-2 antibody titers were higher in the convalescent plasma group two days after the infusion. There were no significant differences with regard to overall adverse events or serious adverse events incidence.

“We believe the use of convalescent plasma as a standard of care in such patients should be reevaluated,” the authors concluded.

In the UK, convalescent plasma is among the various treatments for COVID-19 under investigation in the RECOVERY and the REMAP-CAP trials. According to NHS Blood and Transplant, almost 200,000 people have offered to donate plasma, and more than 32,000 units have been collected.

Richard Haynes, professor of renal medicine and clinical trials in the Nuffield Department of Population Health at the University of Oxford and the clinical trial lead for the RECOVERY trial, told the limbic that the Argentinian trial was far too small to detect what are likely moderate benefits from convalescent plasma therapy.

“The RECOVERY trial will include at least 5,000 people, so RECOVERY will have a lot better chance of identifying the true effect of convalescent plasma,” he said. “The available data suggest there is no major hazard of convalescent plasma, but they have not been large enough yet to tell us whether there are any benefits.”

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