US has jumped the gun on convalescent plasma, critics warn

Transfusion medicine

25 Aug 2020

Australian experts have responded with a mix of caution and scepticism to the US Food and Drug Administration (FDA) emergency authorisation for the use of convalescent plasma to treat COVID-19 patients.

While convalescent plasma is a promising therapy for COVID-19, it should still be considered experimental, according to Associate Professor Steven Tong, a Royal Melbourne Hospital Infectious Diseases Physician who is leading Australian trials of the therapy.

“Despite the recent announcement by President Trump, there has not been clear evidence from randomised controlled trials demonstrating a clinical benefit of convalescent plasma compared to the best standard of care,” he said.

In Australia there are two clinical trials testing convalescent plasma. ASCOT is for hospitalised patients who are not on a ventilator, and REMAP-CAP is for patients in intensive care units.

“In these trials, patients will be randomly assigned to the best standard of care or the best standard of care plus convalescent plasma. The convalescent plasma is being provided by Australian Red Cross Lifeblood,” said Professor Tong, who is Principal Investigator for ASCOT at the Peter Doherty Institute for Infection and Immunity at The University of Melbourne.

The Australian Lead Investigator for convalescent plasma domain REMAP-CAP is Associate Professor Zoe McQuilten, a haematologist at Monash Health and Deputy Director of the Transfusion Research Unit at Monash University.

She said there is good evidence for the safety of convalescent plasma but proof of effectiveness is needed from well-designed randomised controlled trials.

“Such trials have commenced but have not yet been completed. Until such trials are completed and reported, the effectiveness of convalescent plasma remains uncertain,” said Professor McQuilten, who is also Co-Chair of convalescent plasma domain ASCOT.

Some experts have said convalescent plasma is unlikely to be a magic bullet for COVID-19 because of the uncertainties and difficulties of obtaining consistent supplies of plasma containing effective levels of anti-COVID-19 antibodies.

“Convalescent plasma transfusion is absolutely not a practical pathway to population protection – there are too many scaling issues. However, it may still have value for treating critically-ill patients at the local level ” said Professor Jeremy Nicholson, Pro-Vice Chancellor for Health Sciences and Director of the Australian National Phenome Center at Murdoch University.

“The virus itself causes variable seroconversion in infected patients and the antibodies do not appear to be particularly stable – though it is still too early to be certain. That means selection of recovered patients for obtaining blood plasma to transfuse will be hit or miss and difficult to standardise.

He also cautioned that convalescent plasma misses out on the acquired cell-mediated immunity pathway that might be the most critical in fighting off coronavirus, and this will limit the efficacy of plasma transfusions.

The FDA was strongly criticised by clinicians when a spokesperson falsely claimed on social media that convalescent plasma had been shown to be effective in 35% of patients.

Doctors said the FDA statement was simply incorrect, and was a misinterpretation of early data from an unreviewed pre-print publication that showed a reduction in mortality from 11.9% to 8.7% in a small subset of patients treated with convalescent plasma.

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