Nature https://doi.org/10.1038/s41586-021-03710-0 (2021)

Respiratory epithelium is the primary target of SARS-CoV-2; however, sporadic reports of neurological symptoms associated with COVID-19 suggest that the virus may either directly or indirectly target the central nervous system. In Nature, Wyss-Coray and colleagues use single-cell analysis to compare post mortem brain samples from individuals who had COVID-19 with samples from a patient with terminal influenza or from non-infected brain tissue. Immunohistochemistry revealed SARS-CoV-2 infection of the barrier vasculature—specifically, the choroid plexus (CP)—in some of the patients with COVID-19, but no overt infection of brain parenchyma. However, transcriptomic analysis found signs of inflammation and activation of antiviral pathways not only in the CP itself but also within the frontal cortex. These characteristic expression changes were not observed in influenza infection. Many gene expression changes in the COVID-19 cohort are shared with neurodegenerative disease, especially those in astrocytes and excitatory neurons. These data suggest that inflammatory signals may ‘ripple out’ from infected CP into the brain parenchyma and thereby mediate the psychiatric manifestations occasionally seen in COVID-19.