Journal Article

DZNE-2024-00265

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19.

Radke, J. ; Meinhardt, J. ; Aschman, T. ; Chua, R. L. ; Farztdinov, V. ; Lukassen, S. ; Ten, F. W. ; Friebel, E.Extern* ; Ishaque, N. ; Franz, J. ; Huhle, V. H. ; Mothes, R. ; Peters, K. ; Thomas, C. ; Schneeberger, S. ; Schumann, E. ; Kawelke, L. ; Jünger, J. ; Horst, V. ; Streit, S. ; von Manitius, R. ; Körtvelyessy, P.Extern* ; Vielhaber, S.Extern* ; Reinhold, D. ; Hauser, A. E. ; Osterloh, A. ; Enghard, P. ; Ihlow, J. ; Elezkurtaj, S. ; Horst, D. ; Kurth, F. ; Müller, M. A. ; Gassen, N. C. ; Melchert, J. ; Jechow, K. ; Timmermann, B. ; Fernandez-Zapata, C. ; Böttcher, C. ; Stenzel, W. ; Krüger, E. ; Landthaler, M. ; Wyler, E. ; Corman, V.Extern* ; Stadelmann, C. ; Ralser, M. ; Eils, R. ; Heppner, F. L.DZNE* ; Mülleder, M. ; Conrad, C. ; Radbruch, H.

2024
Nature America New York, NY

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Please use a persistent id in citations: doi:10.1038/s41593-024-01573-y

Abstract: 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.

Keyword(s): Humans (MeSH) ; COVID-19: genetics (MeSH) ; Proteomics (MeSH) ; Brain Stem (MeSH) ; Cerebellum (MeSH) ; Gene Expression Profiling (MeSH)

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Contributing Institute(s):

1. Neuroimmunology (AG Heppner)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 20 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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