In a world holding its breath for a vaccine, it’s easy to forget immunization is only one piece of the puzzle. A person who already has COVID-19 needs treatment, and our current treatment options are very limited.
A University of Ottawa team, led by Dr. Alan Tinmouth and Dr. Dean Fergusson, is part of a collaboration aiming to settle the long-standing question of whether “convalescent” blood plasma from recovered patients can be used to treat actively sick ones.
Dr. Tinmouth is an associate professor in uOttawa’s Department of Medicine; Head of General Hematology and Transfusion Medicine at the Ottawa Hospital; and Director of the Ottawa Hospital Research Institute's Centre for Transfusion Research. Dr. Fergusson is a professor in uOttawa’s Departments of Medicine, Surgery, and the School of Epidemiology and Public Health; and Director and Senior Scientist of the Clinical Epidemiology Program at the Ottawa Hospital Research Institute.
The concept behind treatment with convalescent blood plasma is that newly ill patients who haven’t already started making their own antibodies can benefit from the hard-earned wisdom of a veteran immune system. If convalescent plasma can fight the battle against COVID earlier, it might prevent the patient’s condition from deteriorating. The borrowed antibodies would coat the virus and allow the body to clear it, before it can invade more cells.
On the other hand, if it works too well, there is a question of whether a body that has been helped in this way will develop its own long-term immunity as robustly as one that has carried out the battle alone.
Convalescent plasma has a long history of use, including for SARS in Hong Kong, Ebola, and MERS. The infusion practice even dates back to the 1917-18 Spanish Flu. However, it has never been properly studied, using randomized-controlled experiments on a large enough scale to get firm answers.
“There are some studies or reports from the influenza outbreak of 1917 and 1918, but we didn’t even do randomized clinical trials back then—that was only something that started, really, in the 1960s,” says Dr. Tinmouth.
Patients are eligible for this study if they are within twelve days of the onset of symptoms and have become so badly ill that they have been hospitalized and given supplemental oxygen. The patients are randomized into one of two conditions: standard of care (business-as-usual treatments) or convalescent plasma treatment. For every patient assigned to the standard of care control group, on average, two patients are assigned to the experimental condition.
Each patient receives 500mL of plasma that either Canadian Blood Services (CBS) or Héma-Québec has collected from people who have fully recovered. (The blood service first tests the plasma to make sure it contains good antibody levels.) Then the researchers follow the patients for 30 days to see whether or not they end up reaching one or both of two milestones: being intubated and put on a mechanical ventilator, or dying. At the end of the study, a comparison of the two groups will indicate whether the intervention was successful.
“We felt this was an important outcome, because we have been trying to limit the impact on our healthcare system of the number of patients who would be intubated,” says Dr. Tinmouth. “Obviously that’s also a poor outcome for the individual patient as well.”
Based on the natural history of hospitalized patients, the team estimates they will see about a 30% rate of intubation for patients receiving normal care. They hope to show they can reduce that number to about 22.5% through the use of convalescent plasma. But to make that statistical case, they need 1,200 subjects—800 receiving plasma and 400 in the control condition. To Tinmouth’s knowledge, that makes it the largest study of convalescent plasma so far in the world, and it involves several collaborators, including the broader resources of the Canadian Transfusion Research Network, Sunnybrook Hospital in Toronto, Hamilton Health Sciences, St. Justine in Montreal, and, soon, Cornell University in the United States.
A finding that convalescent plasma works would change medical practice far beyond the current crisis. It could become part of the long-term COVID solution if the novel coronavirus proves too mutable for an enduring single vaccine. As well, it could be used as a treatment or prophylactic for other infectious diseases.
The collaboration has already randomized patients in Montreal and Toronto, and it will start this week in Ottawa. In the meantime, the researchers face what, for the rest of us, is a good problem: the number of hospitalized patients is going down at the moment. They will have to scramble to fill their quota of subjects—that is, until a future upswing makes them plentiful.
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