TY  - JOUR
AU  - Radke, Josefine
AU  - Meinhardt, Jenny
AU  - Aschman, Tom
AU  - Chua, Robert Lorenz
AU  - Farztdinov, Vadim
AU  - Lukassen, Sören
AU  - Ten, Foo Wei
AU  - Friebel, Ekaterina
AU  - Ishaque, Naveed
AU  - Franz, Jonas
AU  - Huhle, Valerie Helena
AU  - Mothes, Ronja
AU  - Peters, Kristin
AU  - Thomas, Carolina
AU  - Schneeberger, Shirin
AU  - Schumann, Elisa
AU  - Kawelke, Leona
AU  - Jünger, Julia
AU  - Horst, Viktor
AU  - Streit, Simon
AU  - von Manitius, Regina
AU  - Körtvelyessy, Peter
AU  - Vielhaber, Stefan
AU  - Reinhold, Dirk
AU  - Hauser, Anja E
AU  - Osterloh, Anja
AU  - Enghard, Philipp
AU  - Ihlow, Jana
AU  - Elezkurtaj, Sefer
AU  - Horst, David
AU  - Kurth, Florian
AU  - Müller, Marcel A
AU  - Gassen, Nils C
AU  - Melchert, Julia
AU  - Jechow, Katharina
AU  - Timmermann, Bernd
AU  - Fernandez-Zapata, Camila
AU  - Böttcher, Chotima
AU  - Stenzel, Werner
AU  - Krüger, Elke
AU  - Landthaler, Markus
AU  - Wyler, Emanuel
AU  - Corman, Victor
AU  - Stadelmann, Christine
AU  - Ralser, Markus
AU  - Eils, Roland
AU  - Heppner, Frank L
AU  - Mülleder, Michael
AU  - Conrad, Christian
AU  - Radbruch, Helena
TI  - Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19.
JO  - Nature neuroscience
VL  - 27
IS  - 3
SN  - 1097-6256
CY  - New York, NY
PB  - Nature America
M1  - DZNE-2024-00265
SP  - 409 - 420
PY  - 2024
AB  - 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.
KW  - Humans
KW  - COVID-19: genetics
KW  - Proteomics
KW  - Brain Stem
KW  - Cerebellum
KW  - Gene Expression Profiling
LB  - PUB:(DE-HGF)16
C6  - pmid:38366144
DO  - DOI:10.1038/s41593-024-01573-y
UR  - https://pub.dzne.de/record/268524
ER  -