'Serious complications' are more frequent in COVID-19 patients given convalescent plasma, study says, dashing hopes for the treatment

A recovered COVID-19 patient donates blood at the Arnulfo Arias Madrid Hospital, in Panama City, Wednesday, May 13, 2020. (THE CANADIAN PRESS/AP-Arnulfo Franco)

A large Canadian-led study has shown, for now, that not only are the antibodies of recovered COVID-19 patients ineffective when used to treat seriously ill patients - but that convalescent plasma can even be harmful in certain circumstances.

The serious complications include an increased risk of intubation. There was also an increased risk of death.

The research involving Ste-Justine Hospital physician Dr. Philippe Begin as a co-principal investigator was published Thursday in the journal Nature Medicine.

Convalescent plasma consists of the antibody-containing liquid portion of a recovered person’s blood. The hypothesis was that once transfused to a sick patient, the antibodies would help the patient’s immune system fight the disease.

When the complete results were analyzed it wasn’t the lack of the treatment’s benefits that surprised investigators since the preliminary results of the CONCOR-1 study were equally underwhelming and prompted trial coordinators to stop recruitment last winter.

But some in the scientific community were taken aback by convalescent plasma’s serious downside - an increased risk for the patients’ health.

“That's what changes everything because according to many, it wasn't even considered possible," Begin said, but “overall, in our study, there were statistically more adverse events in the plasma group than in the non-plasma group.”

As a result, the researchers are urging clinicians to be cautious about using convalescent plasma outside of a research protocol, especially when they don’t have information about the antibody content.

BETTER AND WORSE ANTIBODY PROFILES

The study enrolled 940 patients in 73 hospitals in Canada, the United States, and Brazil for the randomized, controlled study.

Researchers say they were able to demonstrate that the specific antibody profile of the convalescent plasma administered had much to do with the effects on the patients.

According to information released by Ste Justine Hospital, the effect was determined by two distinct functions: the ability to neutralize the virus by interfering with its ability to invade the cell, or the ability to harness the power of the immune system to attack infected cells.

It’s this second function that could explain the negative effect of some plasmas.

"We know that not all antibodies have the same ability to activate the immune system. If dysfunctional antibodies are transfused, they can take the place of the patient's own antibodies against the virus, and ultimately interfere with the natural immune response,” Begin explained in a release.

The worst plasma, Begin said, seems to have a lot of antibodies, but with the wrong function.

Patients who received plasma with an antibody profile described as “good” had a comparable risk of intubation and death to that of the control group.

However, patients who received an “unfavourable’ antibody profile ”had a higher mortality rate,” the hospital reported.

MORE STUDIES NEEDED

While this was Canada’s largest clinical trial on convalescent plasma and COVID-19, and its findings are consistent with other studies, it does not mean that the book is closed, said Begin.

Now that many people have recovered from COVID-19 and have also been doubly vaccinated, “the antibody profile is extremely good for both neutralization and immune activation function," he said.

So Begin said it’s still possible convalescent plasma could hold promise as a treatment, but different antibody profiles will have to be properly evaluated before they know for certain. 

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