Plasma doesn’t help patients

 Blood transfusions from people who recovered from the disease didn’t help patients improve — and in some cases made them sicker, according to a major clinical trial.

By Gillian Rutherford

Giving severely ill COVID-19 patients a transfusion of blood from donors who have already recovered from the virus did not help them improve — and in some cases made them sicker, according to a major Canadian-led clinical trial reporting results in Nature Medicine.

“Convalescent plasma had been found to boost immunity in patients infected with some other viral entities, including SARS, in the past,” said local principal investigator Susan Nahirniak, professor of laboratory medicine and pathology in the University of Alberta’s Faculty of Medicine & Dentistry and medical/scientific lead for the Alberta Precision Laboratories transfusion and transplantation medicine program.

“But this trial did not demonstrate any benefit in terms of changing the course for patients who were admitted to hospital needing oxygen for SARS-CoV-2,” Nahirniak said. “It did not prevent intubation or death.”

The randomized controlled study followed 921 COVID-19 patients in Canada, the United States and Brazil who were admitted to hospital within 12 days of the onset of their respiratory symptoms. Two-thirds (614 patients) received convalescent plasma transfusions and one-third (307 patients) did not.

Of the convalescent plasma group, 199 of the patients required intubation or died, while 86 patients in the control group had these outcomes. Patients in the convalescent arm also experienced more serious adverse events such as needing more oxygen or worsening respiratory failure. The trial was terminated early when researchers realized the outcomes were not positive.

Varying immune responses

Another finding of the trial was that the level of neutralizing antibodies, or titres, in the blood of recovered COVID-19 patients was highly variable, which may have implications for how the population responds to vaccination.

“We were finding that several of the people who had signed up as donors were dropping their titres fairly quickly, so maintaining that donor pool was a challenge,” said Nahirniak. 

“It is proof that just because you’ve had COVID once doesn’t mean you can’t have it again,” she said. “It reinforces the need to be vigilant and possibly give boosters, similar to what we do with influenza.”

At the same time, the research team found that some donors had higher levels of non-functional antibodies against the virus’s spike protein. They reported that recipients of this plasma seemed to have poorer outcomes and recommended continued research on the prevalence and impact of these antibodies.

“If COVID is part of our lives going forward and there are certain antibodies that could be potentially harmful, is that something we need to be testing for and screening out for plasma donors?” Nahirniak posited.

Nahirniak noted that participating in the trial during the early days of the COVID-19 pandemic, when few treatments had been identified, helped to boost morale for both patients and clinical staff.

“We felt like we could do nothing, so at least this was an option, identifying the patients early on and getting them monitored.”

Nahirniak noted she was surprised by the disappointing results, but “that’s why we do a trial — we anticipated better success against the virus.”

The study was funded by the Canadian Institutes of Health Research and numerous local health agencies, including the University of Alberta Hospital Foundation and Alberta Health Services.