Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation.
COVID-19
H1N1 influenza
cognitive impairment
hippocampal neurogenesis
long COVID
microglia
myelin
neuroinflammation
oligodendrocytes
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
07 07 2022
07 07 2022
Historique:
received:
07
01
2022
revised:
04
05
2022
accepted:
07
06
2022
pubmed:
30
6
2022
medline:
14
7
2022
entrez:
29
6
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35768006
pii: S0092-8674(22)00713-9
doi: 10.1016/j.cell.2022.06.008
pmc: PMC9189143
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2452-2468.e16Subventions
Organisme : NEI NIH HHS
ID : R01 EY033353
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM145402
Pays : United States
Organisme : NINDS NIH HHS
ID : K23 NS109284
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA124435
Pays : United States
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : T32 GM007365
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007019
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009302
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIAID NIH HHS
ID : K08 AI163493
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI157488
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests A.I. served as a consultant for Spring Discovery, Boehringer Ingelheim (Ingelheim, Germany), and Adaptive Biotechnologies. M.M. serves in the scientific advisory board of Cygnal Therapeutics. S.A.L. sits on the scientific advisory board and has a financial interest in AstronauTx Ltd. The opinions and assertions expressed herein are those of the authors and do not reflect the official policy or position of the Uniformed Services University of the Health Sciences or the Department of Defense.
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