Covid-19: what impact of SARS-CoV-2 infection on the vascular supply of the brain? – Inserm (press room)

Fluorescent image of post-mortem human brain tissue showing cell nuclei (blue) highlighting a blood vessel in which vascular endothelial cells express SARS-CoV2 genetic material (red). © Vincent Prévot / Inserm

Many researchers are currently mobilized to increase knowledge about the SARS-CoV2 virus, for better management of infected patients, but also to try to predict the future consequences of an infection on health. As part of an international collaboration, researchers from Inserm, from the University, the CHU and from the Institut Pasteur de Lille, within the “Lille neuroscience & cognition” laboratory, and colleagues from the CNRS[1], identify for the first time a direct effect of SARS-CoV-2 on the blood vessels of the brain. Certain cells, the cerebral vascular endothelial cells, essential components of the blood-brain barrier that protects the brain, are affected by a phenomenon of cell death. These results, which are the subject of a publication in the journal Nature Neuroscience, particularly ask about the long-term consequences of the disease.

Blood vessels are made up of endothelial cells. Among them are the vascular endothelial cells of the brain that make up the blood-brain barrier (BBB). The main function of the BBB is to isolate the central nervous system from the bloodstream, preventing foreign substances or potentially toxic molecules from entering the brain and spinal cord, while allowing the transfer of nutrients essential for their activity. . Participating in this effort, the vascular endothelial cells of the brain therefore play an essential role in the good blood supply to the brain and their survival is essential for its proper functioning.

As part of an international collaboration funded by the European Research Council[3], the authors of the study looked at vascular endothelial cells in the brain and the consequences of SARS-CoV-2 infection on their functioning.

Thanks to preclinical study models but also by studying the cortex of patients who died as a result of SARS-CoV-2 infection, the researchers show that the infection would lead to the death of endothelial cells in the brain, which would give rise to the appearance of “ghost vessels” in the brain (ie empty tubes, without endothelial cells).

As a result, these essential cells could no longer perform their function at the level of the blood-brain barrier.

How does this endothelial cell death occur? What are the mechanisms involved? Thanks to cutting-edge techniques[2], the team discovered that SARS-CoV-2 causes the endothelial cells it infects to make molecular scissors from its own genetic material. These scissors will cut a protein called NEMO, essential for the survival of endothelial cells, which will therefore die.

The consequences of the death of endothelial cells on the functioning of the brain

According to scientists, the death of vascular endothelial cells in the brain can have two major consequences:

• A temporary rupture of the blood-brain barrier causing microhemorrhages in areas where blood is not supposed to access freely.
• Hypoperfusion of certain regions of the brain (due to the presence of non-functioning phantom vessels), that is to say a decrease in blood flow which can lead to the death of patients in the most serious cases.

However, the study reveals that the situation is reversible.

In addition, scientists are wondering about the long-term consequences of this phase of vulnerability during which the brain of patients is less irrigated. According to them, even if this hypothesis has yet to be verified, this window of time could predispose some people who have contracted the disease to develop cognitive disorders, neurodegenerative disorders, or even dementias.

“This awareness of the seriousness of the SARS-CoV2 infection and its consequences for the proper functioning of our brain is essential to allow the best possible management of patients who have been infected in the years to come. », Concludes Vincent Prévot, research director at Inserm.

[1] Within the Lille Infection and Immunity Center (CNRS / Inserm / Institut Pasteur de Lille / University of Lille / CHU de Lille)

[2] Such as transgenesis, single cell RNA sequencing, mass spectrometry, and super-resolution microscopy.

[3] Program funded by the European Research Council (ERC Synergy) involving Drs. Prévot (Inserm, France), Nogueiras (University of Santiago de Compostela, Spain) and Schwaninger (University of Lübeck, Germany).