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When ‘mild’ COVID-19 is not so mild

Neurological symptoms are common even after ‘mild’ COVID-19. Using a mouse model of SARS-CoV-2 infection limited to the respiratory tract, this study shows that even after viral clearance, there is prolonged microglial reactivity in subcortical and hippocampal white matter and increased levels of CCL11 in the cerebrospinal fluid. Loss of myelin-forming oligodendrocytes and reduced hippocampal neurogenesis were also observed. CCL11 administration in mice causes hippocampal microglial reactivity and impaired hippocampal neurogenesis. Increased plasma levels of CCL11 were also observed in patients with Long COVID with cognitive symptoms, and white matter microglial reactivity was observed in patients who died while infected with SARS-CoV-2 without severe COVID-19. Influenza A virus infection also resulted in neuroinflammation but without the prolonged effects on subcortical white matter.


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Correspondence to Kirsty Minton.

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Minton, K. When ‘mild’ COVID-19 is not so mild. Nat Rev Immunol 22, 463 (2022).

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