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Centre de recherche
Thursday, September 9 2021
Press release

Use of convalescent plasma to treat acute COVID

Large multicentre study at Sainte-Justine University Hospital Centre urges caution

MONTREAL, September 9, 2021 – Although researchers believed that antibodies from COVID-19 patients who had recovered could help fight the severe form of the disease in hospitalized patients, a Canadian-led international multicentre study published today in the journal Nature Medicine reveals much more nuanced results.   

Last winter’s analysis of preliminary results from the CONCOR-1 study showed that transfusion with convalescent plasma does not reduce the risk of intubation or serious complications in patients hospitalized with acute respiratory symptoms caused by COVID-19. At the time, the independent committee recommended that recruitment stop. 

However, the full results of the study published today paint a much more complex picture. A total of 940 patients were randomized in 73 hospitals in Canada, the United States and Brazil.

Antibody transfer: a double-edged sword

Analysis of the complete results did not reveal a significant overall difference in mortality or risk of intubation. However, serious complications were more frequent in patients who received convalescent plasma. Furthermore, the researchers demonstrated that the antibody content largely modulated the clinical effect of convalescent plasma. Patients who had received plasma with a good antibody profile had a risk of mortality and intubation comparable to those in the control group. On the other hand, patients receiving plasma with an unfavourable antibody profile had a higher mortality rate.

The effect of antibodies was determined by two distinct functions: the ability to neutralize the virus by interfering with its entry into the cell or the ability to mobilize the immune system to attack infected cells.

According to Dr. Philippe Bégin, co-principal investigator of the CONCOR-1 study and clinician-researcher at CHU Sainte-Justine and the Université de Montréal Hospital Research Centre (CHUM), it's this second function that could explain the detrimental 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." 

Valuable collaboration

Researcher Andrés Finzi and his team at the CHUM Research Centre developed several of the serological tests used to measure and qualify the immune response in the convalescent plasma of CONCOR-1 patients, including the ADCC (Antibody-Dependent Cellular Cytotoxicity) test, which measures the capacity of antibodies to mobilize the immune system. "The ADCC response is associated with a better patient prognosis, regardless of neutralization capacity," said Andrés Finzi, who is also a professor at the Université de Montréal. "This measure seems essential to get a complete and accurate picture of the immune response to the virus.  It is very promising and is the subject of further work so as to better understand how it functions."  

Dr. Bégin points out that these findings from Canada's largest clinical trial of convalescent plasma in COVID-19 are consistent with other studies showing no effect of convalescent plasma. However, since the plasmas used in the study were collected before the vaccination campaign, that the plasma of convalescent and fully vaccinated patients could be effective cannot be discounted, but this remains to be demonstrated in a clinical trial.

In the meantime, the authors urge caution in using convalescent plasma outside of research, especially in the absence of antibody content analysis. 

The CONCOR-1 study was co-directed by doctors Philippe Bégin, clinician-researcher at CHU Sainte-Justine and CHUM, Donald Arnold, hematologist and professor of medicine at McMaster University, and Jeannie Callum, research associate at Sunnybrook Research Institute.

About the CONCOR-1 study

CONCOR-1 was an open-label randomized controlled trial of convalescent plasma or standard of care for hospitalized adults with COVID-19 acute respiratory illness. The study excluded COVID-19 patients who did not require hospitalization and COVID-19 inpatients who required intubation at the time of hospital admission.

This international collaboration included academic and community hospitals, a patient advisory committee and four blood agencies – Canadian Blood Services, Héma-Québec, the New York Blood Center and Hemorio.

The $5.5 million trial was funded by the Canadian Institutes of Health Research, Canadian Blood Services, Héma-Québec, the Ontario Research Fund, the Ministère de l'Économie et de l'Innovation du Québec, the University of Toronto, Saskatchewan Health, Hamilton Health Science Organization, Sunnybrook Academic Health Sciences Centre, University Health Network, McMaster University, University Health Foundation at the University of Alberta Hospital, Sunnybrook Hospital Foundation, CHU Sainte-Justine Foundation and through the generosity of many private donors.

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About the CHU Sainte-Justine Research Centre

The CHU Sainte-Justine Research Centre is a leading mother-child research institution affiliated with the Université de Montréal. It brings together more than 210 research investigators, including over 110 clinician-scientists, as well as 450 graduate and postgraduate students focused on finding innovative prevention means, faster and less invasive treatments, as well as personalized approaches to medicine. The Centre is part of CHU Sainte-Justine, which is the largest mother-child centre in Canada.

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CHU Sainte-Justine
Contact

For information and interviews:

Justine Mondoux-Turcotte
Media Relations
CHU Sainte-Justine
justine.mondoux.turcotte.hsj@ssss.gouv.qc.ca
514-213-4488

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Updated on 9/8/2021
Created on 9/8/2021
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