COVID-19 causes death of immune cells that are crucial to fight infection

Québec City, February 1, 2022 – An international team has discovered that the COVID-19 virus causes immune cells whose role is to fight COVID-19 infection to self-destruct. The team, co-led by Université Laval and INSERM Professor Jérôme Estaquier, reported that disease severity increases with the death rate of these cells, known as T lymphocytes (or T cells). Details of the discovery were recently published in the scientific journal Cell Death & Differentiation.
 
“Since the start of the pandemic, COVID-19 has been portrayed as a disease that mainly affects the lungs and the inflammatory response, the famous cytokine storm,” said Estaquier, a professor at Université Laval’s Faculty of Medicine and a researcher at the CHU de Québec–Université Laval Research Centre. “Little attention has been paid to the fact that two thirds of patients hospitalized with COVID-19 have abnormally low T cell counts. These cells play a central role in immune response against infections,” added Estaquier, who is also a researcher at France’s Institut national de la santé et de la recherche médicale (INSERM).

Estaquier and his colleagues reviewed the cases of 41 people admitted to hospital with COVID-19. Eleven of them were treated in intensive care due to the severity of their illness. Analyses of blood samples from these patients showed that they had an immune deficiency when they arrived in hospital and that the deficiency was correlated to disease severity.

“SARS-CoV-2 infection sets off a chain reaction that increases levels of the protein FasL in the blood. When this protein binds to a receptor on the surface of T cells, it triggers a type of cell suicide called apoptosis. When levels of the FasL protein are high, more T cells die through protease activation,” Estaquier explained.

This process of programmed T cell death is similar to what happens when a person has AIDS, according to Dr. Estaquier, who has spent nearly 30 years studying HIV: “The same process of T cell apoptosis occurs in the blood of people infected with HIV. As a result, people with either disease have difficulty mounting an adequate immune response against the virus. When too many T cells die, the immune system crumbles, and all the victim’s organs may become infected.” 

The work of Professor Estaquier’s team suggests there may be a way to slow T cell apoptosis in people with COVID-19. “During in vitro experiments, when a Q-VD molecule that blocks protease activation was added to the culture medium, T cell apoptosis fell by 60%. We now intend to start a clinical study to test the safety and efficacy of this inhibitor in people with COVID-19.”

The other study co-leader is Professor Pierre Corbeau, of CNRS-Université de Montpellier and Centre hospitalier de Nîmes. The other study coauthors from Université Laval and CHU de Québec–Université Laval Research Centre are Florence Roux-Dalvai, Clarisse Gotti, Mickaël Leclercq, Gina Racine, Ouafa Zghidi-Abouzid, and Arnaud Droit.