Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy -related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 adminis-tration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuro-pathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cogni-tive impairment following even mild COVID.

Automated summary

COVID survivors may experience lingering neurological symptoms similar to cognitive impairment related to cancer therapy. Research has found that respiratory SARS-CoV-2 infection can cause white-matter-selective microglial reactivity and affect neurogenesis and CCL11 levels.