Evidence suggests SARS-CoV-2 virus attacks brain endothelial cells

A team of researchers affiliated with a large number of institutions in Germany, one in France and one in Spain has found evidence that the SARS-CoV-2 virus attacks brain endothelial cells. In their paper published in the journal Nature Neuroscience, the group describes their study of the brains of people who died of COVID-19.,

Evidence suggests SARS-CoV-2 virus attacks brain endothelial cells
Fig. 1: SARS-CoV-2 infection is associated with increased string vessels in the brain. a-c, In the brains of SARS-CoV-2-infected patients, empty basement membrane tubes, also known as string vessels (arrowheads), were increased in the frontal cortex. Sections were stained for the basement membrane marker collagen IV (coll IV) and the endothelial marker CD34. Representative images in a and b were obtained from the dataset in c. a, Scale bar, 50 um. b, Magnified maximal projection of a z-stack of a string vessel with orthogonal views to exclude that these are partial sections of capillaries. Scale bars, 3 um. c, Quantification of string vessels per image volume. N = 23 control patients, N = 17 COVID-19 patients. d, Immunostaining revealed a higher number of active caspase-3-positive vessels in cortical sections of SARS-CoV-2-infected patients (N = 6) than in controls (N = 6). Representative images and quantification are shown. Scale bar, 20 um. e,f, SARS-CoV-2-infected hamsters developed an increased number of string vessels as shown by co-staining for coll IV and the endothelial marker caveolin-1. e, Representative images of coll IV and caveolin-1 in the cortex of hamsters 4 d post infection (p.i.) with SARS-CoV-2 and of uninfected hamsters. Scale bar, 50 um. f, Quantification of string vessel lengths as a percentage of total vessel length in SARS-CoV-2-infected hamsters at 4, 7 and 24 d p.i. and in uninfected controls (N = 4 hamsters per group). g,h, SARS-CoV-2-infected K18-hACE2 mice developed an increase in string vessels as shown by co-staining for coll IV and caveolin-1. g, Quantification of string vessel lengths as a percentage of total vessel length in SARS-CoV-2-infected K18-hACE2 mice 2 d p.i. (N = 3 mice) and 7 d p.i. (N = 3 mice) and in uninfected controls (N = 5 mice). h, Representative images of coll IV and caveolin-1 in the cortex of K18-hACE2 mice 7 d p.i. and of uninfected K18-hACE2 animals. Scale bar, 50 um. *P

A team of researchers affiliated with a large number of institutions in Germany, one in France and one in Spain has found evidence that the SARS-CoV-2 virus attacks brain endothelial cells. In their paper published in the journal Nature Neuroscience, the group describes their study of the brains of people who died of COVID-19.

Both anecdotal evidence and work by teams studying the impact of the SARS-CoV-2 on the reveal evidence of neurological problems after an infection. Patients have reported a loss of taste and/or smell, and some have experienced what they describe as brain fog. A few have even had strokes or seizures, and many have experienced confusion. Up to now, there has been no physical evidence of the virus attacking cells in the brain, however, which has led researchers to assume that symptoms are the result of inflammation in the brain in response to infection. In this new effort, the researchers have found evidence that the virus attacks in the linings of capillaries that make up the /brain barrier–the first evidence of a direct effect of the SARS-CoV-2 virus on vessels in the brain. The result of such attacks has been death of the cells and blockage of blood flow into the brain.

The work involved studying cerebral vascular endothelial cells, the cells that line the capillaries in the blood/brain barrier, from people who died of COVID-19. The researchers found evidence of dead cells, which resulted in what they describe as ‘ghost vessels’–capillaries through which no blood can flow, leading to damage in the due to oxygen and glucose starvation. More specifically, they found that the virus could split a protein in the endothelial , which resulted in the death of the cell and the destruction of the blood vessel–a process called necroptosis.

On a more optimistic note, the researchers also found that it was possible to prevent necroptosis in mice during an infection, which suggests it might be possible to prevent it in humans as well, hopefully preventing the host of neurological symptoms associated with COVID-19 infections.


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More information:
Jan Wenzel et al, The SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells, Nature Neuroscience (2021). DOI: 10.1038/s41593-021-00926-1

Journal information:
Nature Neuroscience

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