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Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation
Journal article   Open access   Peer reviewed

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

Anthony Fernández-Castañeda, Peiwen Lu, Anna C. Geraghty, Eric Song, Myoung-Hwa Lee, Jamie Wood, Michael R. O’Dea, Selena Dutton, Kiarash Shamardani, Kamsi Nwangwu, …
Cell, Vol.185(14), pp.2452-2468
06/13/2022
DOI: 10.1016/j.cell.2022.06.008
PMCID: PMC9189143
PMID: 35768006
url
https://doi.org/10.1016/j.cell.2022.06.008View
Published (Version of record) Open Access

Abstract

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 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared to 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 timepoints, but after influenza only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID. [Display omitted]
cognitive impairment COVID-19 H1N1 influenza hippocampal neurogenesis long-COVID microglia myelin neuroinflammation oligodendrocytes

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