1. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation.
- Author
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Fernández-Castañeda, Anthony, Lu, Peiwen, Geraghty, Anna C., Song, Eric, Lee, Myoung-Hwa, Wood, Jamie, O'Dea, Michael R., Dutton, Selena, Shamardani, Kiarash, Nwangwu, Kamsi, Mancusi, Rebecca, Yalçın, Belgin, Taylor, Kathryn R., Acosta-Alvarez, Lehi, Malacon, Karen, Keough, Michael B., Ni, Lijun, Woo, Pamelyn J., Contreras-Esquivel, Daniel, and Toland, Angus Martin Shaw
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MICROGLIA , *OLIGODENDROGLIA , *POST-acute COVID-19 syndrome , *COVID-19 , *CENTRAL nervous system , *MYELIN , *CEREBROSPINAL fluid , *WHITE matter (Nerve tissue) - 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 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 neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID. [Display omitted] • Respiratory COVID induces CSF cytokine elevation and microglial reactivity • CCL11 activates hippocampal microglia and impairs neurogenesis • Respiratory COVID causes persistent loss of oligodendrocytes and myelinated axons • Respiratory influenza causes similar but less persistent cellular dysregulation Mild respiratory COVID causes neuroinflammation and multi-lineage cellular dysregulation in the central nervous system, a phenomenon mirroring cancer-therapy-related cognitive impairment. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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