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Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions

COVID-19 can cause severe neurological symptoms, but the underlying pathophysiological mechanisms are unclear. Here, we interrogated the brain stems and olfactory bulbs in postmortem patients who had COVID-19 using imaging mass cytometry to understand the local immune response at a spatially resolve...

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Hauptverfasser: Schwabenland, Marius (VerfasserIn) , Salié, Henrike (VerfasserIn) , Tanevski, Jovan (VerfasserIn) , Killmer, Saskia (VerfasserIn) , Lago, Marilyn Salvat (VerfasserIn) , Schlaak, Alexandra Emilia (VerfasserIn) , Mayer, Lena (VerfasserIn) , Matschke, Jakob (VerfasserIn) , Püschel, Klaus (VerfasserIn) , Fitzek, Antonia (VerfasserIn) , Ondruschka, Benjamin (VerfasserIn) , Mei, Henrik E. (VerfasserIn) , Boettler, Tobias (VerfasserIn) , Neumann-Haefelin, Christoph (VerfasserIn) , Hofmann, Maike (VerfasserIn) , Breithaupt, Angele (VerfasserIn) , Genc, Nafiye (VerfasserIn) , Stadelmann, Christine (VerfasserIn) , Sáez Rodríguez, Julio (VerfasserIn) , Bronsert, Peter (VerfasserIn) , Knobeloch, Klaus-Peter (VerfasserIn) , Blank, Thomas (VerfasserIn) , Thimme, Robert (VerfasserIn) , Glatzel, Markus (VerfasserIn) , Prinz, Marco (VerfasserIn) , Bengsch, Bertram (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 9 June 2021
In: Immunity
Year: 2021, Jahrgang: 54, Heft: 7, Pages: 1594-1610, e1-e11
ISSN:1097-4180
DOI:10.1016/j.immuni.2021.06.002
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.immuni.2021.06.002
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1074761321002466
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Verfasserangaben:Marius Schwabenland, Henrike Salié, Jovan Tanevski, Saskia Killmer, Marilyn Salvat Lago, Alexandra Emilia Schlaak, Lena Mayer, Jakob Matschke, Klaus Püschel, Antonia Fitzek, Benjamin Ondruschka, Henrik E. Mei, Tobias Boettler, Christoph Neumann-Haefelin, Maike Hofmann, Angele Breithaupt, Nafiye Genc, Christine Stadelmann, Julio Saez-Rodriguez, Peter Bronsert, Klaus-Peter Knobeloch, Thomas Blank, Robert Thimme, Markus Glatzel, Marco Prinz, and Bertram Bengsch

MARC

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520 |a COVID-19 can cause severe neurological symptoms, but the underlying pathophysiological mechanisms are unclear. Here, we interrogated the brain stems and olfactory bulbs in postmortem patients who had COVID-19 using imaging mass cytometry to understand the local immune response at a spatially resolved, high-dimensional, single-cell level and compared their immune map to non-COVID respiratory failure, multiple sclerosis, and control patients. We observed substantial immune activation in the central nervous system with pronounced neuropathology (astrocytosis, axonal damage, and blood-brain-barrier leakage) and detected viral antigen in ACE2-receptor-positive cells enriched in the vascular compartment. Microglial nodules and the perivascular compartment represented COVID-19-specific, microanatomic-immune niches with context-specific cellular interactions enriched for activated CD8+ T cells. Altered brain T-cell-microglial interactions were linked to clinical measures of systemic inflammation and disturbed hemostasis. This study identifies profound neuroinflammation with activation of innate and adaptive immune cells as correlates of COVID-19 neuropathology, with implications for potential therapeutic strategies. 
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