Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
16 Feb 2024
16 Feb 2024
Historique:
received:
20
06
2023
accepted:
08
01
2024
medline:
17
2
2024
pubmed:
17
2
2024
entrez:
17
2
2024
Statut:
aheadofprint
Résumé
Neurological symptoms, including cognitive impairment and fatigue, can occur in both the acute infection phase of coronavirus disease 2019 (COVID-19) and at later stages, yet the mechanisms that contribute to this remain unclear. Here we profiled single-nucleus transcriptomes and proteomes of brainstem tissue from deceased individuals at various stages of COVID-19. We detected an inflammatory type I interferon response in acute COVID-19 cases, which resolves in the late disease phase. Integrating single-nucleus RNA sequencing and spatial transcriptomics, we could localize two patterns of reaction to severe systemic inflammation, one neuronal with a direct focus on cranial nerve nuclei and a separate diffuse pattern affecting the whole brainstem. The latter reflects a bystander effect of the respiratory infection that spreads throughout the vascular unit and alters the transcriptional state of mainly oligodendrocytes, microglia and astrocytes, while alterations of the brainstem nuclei could reflect the connection of the immune system and the central nervous system via, for example, the vagus nerve. Our results indicate that even without persistence of severe acute respiratory syndrome coronavirus 2 in the central nervous system, local immune reactions are prevailing, potentially causing functional disturbances that contribute to neurological complications of COVID-19.
Identifiants
pubmed: 38366144
doi: 10.1038/s41593-024-01573-y
pii: 10.1038/s41593-024-01573-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : RA 2491/1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : CRC 130 TP17
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : CRC130 TP17
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : HA 5354/10-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : EXC-2049-390688087
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB TRR 167
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : HE 3130/6-1
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.
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