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000268524 1001_ $$00000-0001-9860-2007$$aRadke, Josefine$$b0
000268524 245__ $$aProteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19.
000268524 260__ $$aNew York, NY$$bNature America$$c2024
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000268524 520__ $$aNeurological 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.
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000268524 650_2 $$2MeSH$$aHumans
000268524 650_2 $$2MeSH$$aCOVID-19: genetics
000268524 650_2 $$2MeSH$$aProteomics
000268524 650_2 $$2MeSH$$aBrain Stem
000268524 650_2 $$2MeSH$$aCerebellum
000268524 650_2 $$2MeSH$$aGene Expression Profiling
000268524 7001_ $$00000-0003-0366-2416$$aMeinhardt, Jenny$$b1
000268524 7001_ $$00000-0002-2101-6146$$aAschman, Tom$$b2
000268524 7001_ $$aChua, Robert Lorenz$$b3
000268524 7001_ $$aFarztdinov, Vadim$$b4
000268524 7001_ $$00000-0001-7045-6327$$aLukassen, Sören$$b5
000268524 7001_ $$aTen, Foo Wei$$b6
000268524 7001_ $$0P:(DE-2719)9002758$$aFriebel, Ekaterina$$b7$$udzne
000268524 7001_ $$00000-0002-8426-901X$$aIshaque, Naveed$$b8
000268524 7001_ $$00000-0001-7523-6622$$aFranz, Jonas$$b9
000268524 7001_ $$aHuhle, Valerie Helena$$b10
000268524 7001_ $$aMothes, Ronja$$b11
000268524 7001_ $$aPeters, Kristin$$b12
000268524 7001_ $$00000-0002-7386-1181$$aThomas, Carolina$$b13
000268524 7001_ $$aSchneeberger, Shirin$$b14
000268524 7001_ $$aSchumann, Elisa$$b15
000268524 7001_ $$aKawelke, Leona$$b16
000268524 7001_ $$aJünger, Julia$$b17
000268524 7001_ $$aHorst, Viktor$$b18
000268524 7001_ $$aStreit, Simon$$b19
000268524 7001_ $$avon Manitius, Regina$$b20
000268524 7001_ $$0P:(DE-2719)2812030$$aKörtvelyessy, Peter$$b21$$udzne
000268524 7001_ $$0P:(DE-2719)2000035$$aVielhaber, Stefan$$b22$$udzne
000268524 7001_ $$00000-0002-6441-9631$$aReinhold, Dirk$$b23
000268524 7001_ $$aHauser, Anja E$$b24
000268524 7001_ $$aOsterloh, Anja$$b25
000268524 7001_ $$aEnghard, Philipp$$b26
000268524 7001_ $$aIhlow, Jana$$b27
000268524 7001_ $$00000-0002-1699-1270$$aElezkurtaj, Sefer$$b28
000268524 7001_ $$aHorst, David$$b29
000268524 7001_ $$00000-0002-3807-473X$$aKurth, Florian$$b30
000268524 7001_ $$00000-0003-2242-5117$$aMüller, Marcel A$$b31
000268524 7001_ $$00000-0002-4265-3398$$aGassen, Nils C$$b32
000268524 7001_ $$00000-0002-0494-1022$$aMelchert, Julia$$b33
000268524 7001_ $$aJechow, Katharina$$b34
000268524 7001_ $$aTimmermann, Bernd$$b35
000268524 7001_ $$00000-0003-4795-6053$$aFernandez-Zapata, Camila$$b36
000268524 7001_ $$0P:(DE-2719)9000034$$aBöttcher, Chotima$$b37
000268524 7001_ $$aStenzel, Werner$$b38
000268524 7001_ $$00000-0002-2551-242X$$aKrüger, Elke$$b39
000268524 7001_ $$00000-0002-1075-8734$$aLandthaler, Markus$$b40
000268524 7001_ $$00000-0002-9884-1806$$aWyler, Emanuel$$b41
000268524 7001_ $$0P:(DE-2719)9001090$$aCorman, Victor$$b42$$udzne
000268524 7001_ $$00000-0003-1766-5458$$aStadelmann, Christine$$b43
000268524 7001_ $$00000-0001-9535-7413$$aRalser, Markus$$b44
000268524 7001_ $$aEils, Roland$$b45
000268524 7001_ $$0P:(DE-2719)2812386$$aHeppner, Frank L$$b46
000268524 7001_ $$00000-0001-9792-3861$$aMülleder, Michael$$b47
000268524 7001_ $$00000-0001-7036-342X$$aConrad, Christian$$b48
000268524 7001_ $$00000-0001-6941-3397$$aRadbruch, Helena$$b49
000268524 773__ $$0PERI:(DE-600)1494955-6$$a10.1038/s41593-024-01573-y$$gVol. 27, no. 3, p. 409 - 420$$n3$$p409 - 420$$tNature neuroscience$$v27$$x1097-6256$$y2024
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