Insights into How SARS-CoV-2 Causes Brain Pathology

Authors: Anthony L. Komaroff, MD, reviewing Yang AC et al. Nature 2021 Jul Marshall M. Nature 2021 Jul

In deceased COVID-19 patients, gene expression in the choroid plexus was altered.

People infected with SARS-CoV-2 can develop a wide variety of neurological conditions: Endothelial dysfunction can lead to ischemic and hemorrhagic strokes, even in young adults. Demyelinating diseases occur. Autoantibodies that affect the function of neural targets have been identified. The virus also can infect astrocytes, although infection appears to be short lived.

Investigators painstakingly measured gene expression (i.e., RNAs being transcribed) inside the nuclei of individual cells from 8 deceased older adults with COVID-19, 1 person who died from influenza, and 13 older control subjects. All told, 65,309 cells of 14 different types from different parts of the brain were evaluated, including neurons, glial cells (the innate immune cells of the brain), and cells of the choroid plexus involved in the blood–brain barrier. Among COVID-19 patients, gene-expression patterns in cells of the choroid plexus and in glial cells were very different from patterns in control patients — and the COVID-19 patterns were similar, although not identical, to patterns seen in patients with several neurodegenerative diseases (including dementias and schizophrenia). Synaptic signaling was impaired in the excitatory neurons that are important in cognition. There was no evidence of SARS-CoV-2 in the brain at the time of autopsy.

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