Convalescent plasma could harm the health of patients with COVID-19 under certain circumstances, shows a new study published by researchers at CHU Sainte-Justine in the medical journal Nature Medicine.
The use of convalescent plasma – a treatment that involves transfusing a sick patient with the liquid portion of the blood of a cured patient so that the patient’s antibodies fight the virus – has long been justified by the fact that the procedure, even if it were to prove ineffective, could not harm patients.
Doctor Philippe Bégin and his colleagues have just demonstrated that this premise is wrong.
“This is what actually changes everything, because according to many, it was not even considered possible,” he explained to The Canadian Press.
Dr. Bégin himself co-directed an international study at Sainte-Justine on the effectiveness of convalescent plasma. The work was halted in February when the committee of independent experts concluded, on the basis of the data collected so far, that their continuation would not allow any efficacy to be demonstrated.
Analysis of the data continued, however, leading to “nonetheless surprising results,” he said.
“Overall, in our study, overall, we had statistically more adverse effects in the group that received plasma than in the group that did not receive plasma,” summarized Dr. Bégin.
It was therefore apparently wrong to believe, as was the case in the beginning, that there was nothing to lose by administering convalescent plasma to patients.
Collateral victim
The study of convalescent plasma appears to have been a collateral victim of the COVID-19 pandemic.
Faced with an unprecedented health crisis, scientists around the world hastened to explore all the avenues that seemed in the slightest promising to combat the coronavirus. But in this haste, the scientific rigor that would otherwise have been required has sometimes been abused.
Several of the studies which pointed in the direction of an efficiency of convalescent plasma had, for example, been carried out without a control group. It is moreover on the basis of such studies that the powerful Food and Drug Administration of the United States granted in the fall an emergency authorization for the use of convalescent plasma.
In addition, some studies involved plasma rich in antibodies, others in less concentrated plasma, still others in both products, which ended up causing some confusion.
“So, based on an uncontrolled study showing that plasma with more antibody concentration saved more lives than less concentrated, many concluded that plasma could save lives, when in fact it was probably the reverse, said Dr. Bégin. In retrospect, it seems rather to be the weakly concentrated that increased mortality […] than the highly concentrated that helped.
“Across the world, we opened the floodgates to treatment on a potentially misreading science because we didn’t do a control group. Just in the United States, there are over 500,000 people who have been treated with this. “
In his study, Dr. Bégin thus observed an increase in the rate of mortality and intubation in patients who had received weakly concentrated plasma. In contrast, these rates were similar when comparing untreated patients and patients who received plasma rich in neutralizing antibodies.
Antibody
As antibodies are not all created equal in the fight against COVID-19, Dr. Bégin also took advantage of his study to study them in more depth.
While the ability of antibodies to neutralize the virus to prevent it from infecting cells is the one that receives the most attention, less is said about their ability to activate the immune system.
“The antibodies it’s Y-shaped and the tail of the Y is to activate the immune system and that does a lot of other things, (but) we were just focusing on neutralization,” he said.
If we only look at neutralization, he explains, there would be no reason why a plasma that contains little or no antibodies, or that contains the wrong antibodies, should not be harmful to health. of the patient. In the worst-case scenario, its neutralization capacity would be somewhat diminished, without that making a big difference in the end.
But if we transfer antibodies that are incapable of activating the immune system to the patient, it is possible that they will take the place of the antibodies produced by the patient and which would have potentially been shown to be more effective.
“In fact, they interfere with the patient’s response, so this is possibly the reason why poor quality plasmas could increase the risk of mortality and intubation,” said Dr. Bégin.
The worst plasma, he says, seems to be the one with a lot of antibodies, but with the wrong function.
In data | Our content on COVID-19
The real life
The studies that have shown a certain effectiveness, or at least an absence of effectiveness, of convalescent plasma all used plasma selected for its high concentration of neutralizing antibodies, added Dr. Bégin. For example, a large British study which brought together 11,000 patients and which concluded that the plasma was not effective had only used highly neutralizing plasma.
But in “real life”, outside of clinical trials, what was used, “it was not highly neutralizing plasma, it is rare for people who had access to neutralizing plasmas or even the ability to test. the level of neutralization, ”he said.
What’s more, centers that used highly neutralizing plasma probably had “other ways to better treat patients.”
“We know that COVID-19 is not democratic,” said Dr. Bégin. If you have fewer resources, you have more mortality. It is obvious that there are biases. “
Convalescent plasma is now kind of a thing of the past, in the United States and elsewhere. New treatments, like monoclonal antibodies, are getting all the attention.
But in some less fortunate countries, which do not have access to advanced technologies, it is often among the only therapies available. These countries should know that the treatment, contrary to what was originally believed, is not necessarily harmless.
In addition, contrary to what was the case at the start of the pandemic, plasmas of “very good quality” could now be more readily available, believes Dr. Bégin.
“They were very rare, these very good plasmas at the start of the pandemic, but now that the patients who have had COVID-19 are being vaccinated, you have had COVID-19 and you are receiving two doses of the vaccine, the Antibody profile is extremely good for both neutralization and activating function of the immune system, ”he said.
The scientific data available at the moment suggests that such a very high quality plasma could be effective, and it would therefore be important to continue the studies – making sure, this time, to respect the rules of art.
“The way we used it didn’t work, that was clear,” concluded Dr. Bégin. But that suggests that if you are able to have very high quality plasma, there are signals that say yes, potentially it could work, but we haven’t demonstrated it. “
Watch video
Reference-feedproxy.google.com