Although COVID-19 primarily affects the respiratory system, many people also report neurological symptoms during and after COVID-19 infection, such as loss of smell, confusion and headaches. Long COVID is associated with cognitive impairment, which can affect a substantial proportion of people recovering from COVID-19, and an increased risk of stroke. However, little is understood about the brain changes that might underly these symptoms, and whether SARS-CoV-2, the virus that causes COVID-19, can directly infect brain cells.
To address these questions, a team of researchers studied brain samples from people who had been infected with SARS-CoV-2, as well as animal models of COVID-19 infection. In an article published in Nature Neuroscience on 21 October, the researchers reported their findings, highlighting the presence of dead endothelial cells in the brains of people who had COVID-19.
Endothelial cells are specialised cells that line the walls of blood vessels, playing an important role in regulating blood flow, clotting, and inflammation. As such, endothelial dysfunction is strongly linked to stroke and vascular cognitive impairment. Studying the brains of people who died from COVID-19, the researchers observed that they often had dead capillaries, indicative of damage to endothelial cells. Looking more closely at clinical samples and animal models of disease, they identified an enzyme (a protease) produced by SARS-CoV-2 as a potential culprit: when human endothelial cells were incubated with the protease, they no longer produced functional NEMO proteins - proteins that ensure endothelial cell survival. Without NEMO, endothelial cells died and, in animal models, brain capillaries withered away when faced with SARS-CoV-2 and its protease. The route for SARS-CoV-2 to reach the brain remains unclear, however; research is continuing to identify if and how the virus that causes COVID-19 can directly infect brain cells in humans.