Scientists have just demonstrated that SARS-CoV-2 has a direct and profound impact on brain function. Using its own genetic material, the virus causes the endothelial cells it infects to form molecular scissors that turn blood vessels into “ghost vessels” (empty tubes with no endothelial cells). What are the consequences of this cell death on brain irrigation?
SARS-CoV-2 and the brain
Many researchers are currently trying to expand our knowledge of SARS-CoV-2, to improve the treatments currently available, and also to try to predict the future health consequences of the infection. Researchers from Inserm and the Pasteur Institute and colleagues from the CNRS have shown that there was a direct effect of SARS-CoV-2 on blood vessels in the brain.
After SARS-CoV-2 infection brain vascular endothelial cells that protect the brain, are destroyed. The results of the study that was, published in the journal Nature Neuroscience, raise questions about the long-term consequences of COVID-19 on cerebral health.
Blood vessels are composed of endothelial cells. These include the vascular endothelial cells of the brain, which form the blood-brain barrier (BBB). The main function of the BBB is to isolate the central nervous system from the bloodstream, preventing the entry of foreign substances or potentially toxic molecules into the brain and spinal cord while allowing the transfer of nutrients essential for its function. As part of this effort, the brain’s vascular endothelial cells play an important role in supplying the brain with blood, and their survival is essential for its proper functioning.
How do molecular scissors cause endothelial cell death?
As part of an international collaboration funded by the European Research Council, the authors of the study analyzed vascular endothelial cells in the brain and the consequences of SARS-CoV-2 infection on their function. Using preclinical models of the study, but also by examining the cerebral cortex of patients who died as a result of SARS-CoV-2 infection, the researchers showed that infection leads to endothelial cell death in the brain, resulting in the formation of ‘ghost vessels’ in the brain, i.e. empty vessels without endothelial cells. As a result, these important cells are no longer be able to fulfill their function in the blood-brain barrier.
How does endothelial cell death occur?
Using state-of-the-art techniques such as transgenesis, single-cell RNA sequencing, mass spectrometry, and super-resolution microscopy, the team found that SARS-CoV-2 causes the endothelial cells it infects to make molecular scissors from their own genetic material. These scissors then cut a protein called Nemo, which is essential for the survival of the endothelial cells, which then die as a result.
What are the implications for brain function?
According to scientists, the death of vascular endothelial cells in the brain may have two main consequences:
Temporary disruption of the blood-brain barrier, which causes microbleeds in areas where blood should not have free access.
Not enough blood going to certain areas of the brain (due to the presence of non-functioning ghost vessels) can lead to the death of the patient in the most severe cases.
However, the study showed that the situation is reversible. Still, the researchers are interested in the long-term consequences of this episode, during which patients’ brains were poorly irrigated. According to them, although this hypothesis has not yet been verified, this could predispose some people who have contracted the disease to develop cognitive and neurodegenerative disorders or even dementia in the future.
There is still a lot that we don’t know about the long-term effects of getting infected with SARS-CoV-2. And it is for this reason that getting vaccinated to prevent getting infected in the first place is still the wisest course. For this reason, it is important to make the general public aware of the severity of SARS-CoV-2 infection and its consequences on the proper functioning of our brains and all our other organs.