A team of researchers led by an immunology specialist from Laval University has just highlighted an important, even central, factor that would be responsible for the development of a serious, even fatal, form of COVID-19. This discovery, which was first made in people infected with HIV, could lead to the development of a test that can predict whether a hospitalized patient is at risk of seeing their condition deteriorate, as well as a drug capable of preventing such a trajectory.
Researchers first observed that the majority of patients hospitalized with COVID-19 had abnormally low blood levels of lymphocytes, cells of the immune system that play a central role in fighting pathogens during a infection. They also found that this immune deficiency was more pronounced in people who ended up in an intensive care unit than in those who had a milder form of the disease.
“When you have less lymphocytes in the blood, it looks like an immunodeficiency, and for someone who has worked on AIDS for almost 30 years, it is puzzling, because patients infected with HIV also have lymphopenia. [déficit de lymphocytes] “, points out Jérôme Estaquier, researcher at the Research Center of the CHU of Quebec-Laval University and at the National Institute of Health and Medical Research (INSERM), in France.
The researchers then suspected the role of a phenomenon that they had observed in the 1990s in the context of their studies on AIDS, namely the programmed death, also called suicide or apoptosis, of lymphocytes. This led them to formulate the hypothesis that an exacerbated process of T cell death in patients with COVID induced an early immune deficiency which was likely to precipitate the patient towards a severe form.
“When you lose your good CD4-type T cells, you also lose the help of B cells that produce neutralizing antibodies capable of blocking the virus, and also potentially cytotoxic cells, killers of infected cells, of the CD8 type. The person who finds himself with an immune system thus weakened, who is unable to fight the virus, will see it spread throughout the body, which would probably lead to a much more serious form from the pathological point of view. It’s a bit similar from a mechanistic point of view to what we can see in AIDS,” explains Estaquier.
A study carried out by researchers from the National Institutes of Health in the United States has shown that in people who died of COVID-19, the virus had spread to a very large number of tissues and organs other than than the lungs, he remarks in this regard.
While working on AIDS, Mr. Estaquier and his colleagues had identified molecules capable of preventing “the death of T lymphocytes”. This time experiences in vitro showed that one of these molecules reduces lymphocyte apoptosis by 60%.
“This molecule could have the beneficial effect of preventing a possible early immune deficiency in people with COVID-19 and thus allowing a better defense against infection,” says Mr. Estaquier.
Resources needed
But to confirm this hypothesis, the researchers will first have to carry out the first phase of a clinical trial which will aim to assess the harmlessness of the molecule in normal healthy people. “To do this, we need to find the financial resources to produce the molecule in a clinical form. The one currently available cannot be administered to humans. We must take this step so that the molecule is produced according to good manufacturing practices, ”he underlines.
“Six months before the pandemic, we were looking for funds to start this stage as part of a pan-Canadian AIDS project. And since we were caught up in the COVID-19, we could not continue these steps. Now, we say to ourselves that this first clinical phase would not only be used for COVID-19, but also for HIV, ”says the researcher, who is the main author of the study in question, the details of which have been published in review Cell Death & Differentiation.
In their study, Mr. Estaquier and his colleagues also discovered in the blood of people hospitalized with COVID-19 a protein which, when it binds to T cells, leads to their suicide. It is a “death ligand called FasL”. This is expressed during infection and will bind to CD4 T lymphocytes and induce them to commit suicide by apoptosis.
However, by going to measure the abundance of this ligand in patients, we could predict which ones are at risk of developing a severe form. “It would be a fairly standard test that could be done in the hospital and that would have potential diagnostic value. It could be used to predict the clinical evolution as well as the management”, specifies the researcher.