Journal article
Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation
Cell, Vol.185(14), pp.2452-2468
06/13/2022
DOI: 10.1016/j.cell.2022.06.008
PMCID: PMC9189143
PMID: 35768006
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.
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Details
- Title: Subtitle
- Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation
- Creators
- Anthony Fernández-Castañeda - Stanford UniversityPeiwen Lu - Yale UniversityAnna C. Geraghty - Stanford UniversityEric Song - Yale UniversityMyoung-Hwa Lee - National Institute of Neurological Disorders and StrokeJamie Wood - Icahn School of Medicine at Mount SinaiMichael R. O’Dea - New York UniversitySelena Dutton - Stanford UniversityKiarash Shamardani - Stanford UniversityKamsi Nwangwu - Stanford UniversityRebecca Mancusi - Stanford UniversityBelgin Yalçın - Stanford UniversityKathryn R. Taylor - Stanford UniversityLehi Acosta-Alvarez - Stanford UniversityKaren Malacon - Stanford UniversityMichael B. Keough - Stanford UniversityLijun Ni - Stanford UniversityPamelyn J. Woo - Stanford UniversityDaniel Contreras-Esquivel - Stanford UniversityAngus Martin Shaw Toland - Stanford UniversityJeff R. Gehlhausen - Yale UniversityJon Klein - Yale UniversityTakehiro Takahashi - Yale UniversityJulio Silva - Yale UniversityBenjamin Israelow - Yale UniversityCarolina Lucas - Yale UniversityTianyang Mao - Yale UniversityMario A. Peña-Hernández - Yale UniversityAlexandra Tabachnikova - Yale UniversityRobert J. Homer - Yale UniversityLaura Tabacof - Icahn School of Medicine at Mount SinaiJenna Tosto-Mancuso - Icahn School of Medicine at Mount SinaiErica Breyman - Icahn School of Medicine at Mount SinaiAmy Kontorovich - Icahn School of Medicine at Mount SinaiDayna McCarthy - Icahn School of Medicine at Mount SinaiMartha Quezado - National Cancer Institute, Bethesda MD USAHannes Vogel - Stanford UniversityMarco M. Hefti - University of IowaDaniel P. Perl - Department of Pathology, Uniformed Services University of Health Sciences, Bethesda MD USAShane Liddelow - New York UniversityRebecca Folkerth - Office of Chief Medical ExaminerDavid Putrino - Icahn School of Medicine at Mount SinaiAvindra Nath - National Institute of Neurological Disorders and StrokeAkiko Iwasaki - Yale UniversityMichelle Monje - Stanford University
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.185(14), pp.2452-2468
- DOI
- 10.1016/j.cell.2022.06.008
- PMID
- 35768006
- PMCID
- PMC9189143
- NLM abbreviation
- Cell
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: NIH
- Language
- English
- Date published
- 06/13/2022
- Academic Unit
- Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984269683902771
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