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Nat Neurosci
. 2024 Feb 16.
doi: 10.1038/s41593-024-01573-y. Online ahead of print. Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19
Josefine Radke # 1 2 , Jenny Meinhardt # 3 , Tom Aschman # 3 , Robert Lorenz Chua # 4 , Vadim Farztdinov # 5 , Sören Lukassen 4 , Foo Wei Ten 4 , Ekaterina Friebel 3 , Naveed Ishaque 4 , Jonas Franz 6 , Valerie Helena Huhle 3 , Ronja Mothes 3 , Kristin Peters 7 , Carolina Thomas 6 , Shirin Schneeberger 3 , Elisa Schumann 3 , Leona Kawelke 3 , Julia Jünger 3 , Viktor Horst 3 , Simon Streit 3 , Regina von Manitius 3 , Péter Körtvélyessy 8 , Stefan Vielhaber 9 , Dirk Reinhold 10 , Anja E Hauser 11 12 , Anja Osterloh 13 , Philipp Enghard 14 , Jana Ihlow 15 , Sefer Elezkurtaj 15 , David Horst 15 , Florian Kurth 16 , Marcel A Müller 17 , Nils C Gassen 18 , Julia Melchert 17 , Katharina Jechow 4 , Bernd Timmermann 19 , Camila Fernandez-Zapata 20 , Chotima Böttcher 20 , Werner Stenzel 3 , Elke Krüger 21 , Markus Landthaler 22 23 , Emanuel Wyler 22 , Victor Corman 16 24 , Christine Stadelmann 6 , Markus Ralser 5 , Roland Eils 4 , Frank L Heppner 3 25 26 27 , Michael Mülleder 5 , Christian Conrad 4 , Helena Radbruch 28
Affiliations
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.
. 2024 Feb 16.
doi: 10.1038/s41593-024-01573-y. Online ahead of print. Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19
Josefine Radke # 1 2 , Jenny Meinhardt # 3 , Tom Aschman # 3 , Robert Lorenz Chua # 4 , Vadim Farztdinov # 5 , Sören Lukassen 4 , Foo Wei Ten 4 , Ekaterina Friebel 3 , Naveed Ishaque 4 , Jonas Franz 6 , Valerie Helena Huhle 3 , Ronja Mothes 3 , Kristin Peters 7 , Carolina Thomas 6 , Shirin Schneeberger 3 , Elisa Schumann 3 , Leona Kawelke 3 , Julia Jünger 3 , Viktor Horst 3 , Simon Streit 3 , Regina von Manitius 3 , Péter Körtvélyessy 8 , Stefan Vielhaber 9 , Dirk Reinhold 10 , Anja E Hauser 11 12 , Anja Osterloh 13 , Philipp Enghard 14 , Jana Ihlow 15 , Sefer Elezkurtaj 15 , David Horst 15 , Florian Kurth 16 , Marcel A Müller 17 , Nils C Gassen 18 , Julia Melchert 17 , Katharina Jechow 4 , Bernd Timmermann 19 , Camila Fernandez-Zapata 20 , Chotima Böttcher 20 , Werner Stenzel 3 , Elke Krüger 21 , Markus Landthaler 22 23 , Emanuel Wyler 22 , Victor Corman 16 24 , Christine Stadelmann 6 , Markus Ralser 5 , Roland Eils 4 , Frank L Heppner 3 25 26 27 , Michael Mülleder 5 , Christian Conrad 4 , Helena Radbruch 28
Affiliations
- PMID: 38366144
- DOI: 10.1038/s41593-024-01573-y
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.