COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with acute and postacute cognitive and neuropsychiatric symptoms including impaired memory, concentration, attention, sleep and affect. Mechanisms underlying these brain symptoms remain understudied. Here we report that SARS-CoV-2-infected hamsters exhibit a lack of viral neuroinvasion despite aberrant blood-brain barrier permeability. Hamsters and patients deceased from coronavirus disease 2019 (COVID-19) also exhibit microglial activation and expression of interleukin (IL)-1 beta and IL-6, especially within the hippocampus and the medulla oblongata, when compared with non-COVID control hamsters and humans who died from other infections, cardiovascular disease, uraemia or trauma. In the hippocampal dentate gyrus of both COVID-19 hamsters and humans, we observed fewer neuroblasts and immature neurons. Protracted inflammation, blood-brain barrier disruption and microglia activation may result in altered neurotransmission, neurogenesis and neuronal damage, explaining neuropsychiatric presentations of COVID-19. The involvement of the hippocampus may explain learning, memory and executive dysfunctions in COVID-19 patients. Soung et al. report that SARS-CoV-2-infected hamsters and patients who died from COVID-19 exhibit increased microglial activation and expression of interleukin (IL)-1 beta and IL-6 within the medulla oblongata and hippocampus, as well as reduced hippocampal neurogenesis, compared with uninfected controls.

Automated summary

Cognitive and neuropsychiatric symptoms associated with COVID-19 may be related to inflammation, blood-brain barrier disruption, and abnormal activation in the hippocampus.