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Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19

Item Type:Article
Title:Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19
Creators Name:Radke, J. and Meinhardt, J. and Aschman, T. and Chua, R.L. and Farztdinov, V. and Lukassen, S. and Ten, F.W. and Friebel, E. and Ishaque, N. and Franz, J. and Huhle, V.H. and Mothes, R. and Peters, K. and Thomas, C. and Schneeberger, S. and Schumann, E. and Kawelke, L. and Jünger, J. and Horst, V. and Streit, S. and von Manitius, R. and Körtvélyessy, P. and Vielhaber, S. and Reinhold, D. and Hauser, A.E. and Osterloh, A. and Enghard, P. and Ihlow, J. and Elezkurtaj, S. and Horst, D. and Kurth, F. and Müller, M.A. and Gassen, N.C. and Melchert, J. and Jechow, K. and Timmermann, B. and Fernandez-Zapata, C. and Böttcher, C. and Stenzel, W. and Krüger, E. and Landthaler, M. and Wyler, E. and Corman, V. and Stadelmann, C. and Ralser, M. and Eils, R. and Heppner, F.L. and Mülleder, M. and Conrad, C. and Radbruch, H.
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.
Keywords:Brain Stem, COVID-19, Cerebellum, Gene Expression Profiling, Proteomics
Source:Nature Neuroscience
Publisher:Nature Publishing Group
Page Range:409–420
Date:March 2024
Official Publication:https://doi.org/10.1038/s41593-024-01573-y
PubMed:View item in PubMed

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