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

ABSTRACT: 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.

SUBMITTER: Schwabenland M

PROVIDER: S-EPMC8188302 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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

Schwabenland Marius M Salié Henrike H Tanevski Jovan J Killmer Saskia S Lago Marilyn Salvat MS Schlaak Alexandra Emilia AE Mayer Lena L Matschke Jakob J Püschel Klaus K Fitzek Antonia A Ondruschka Benjamin B Mei Henrik E HE Boettler Tobias T Neumann-Haefelin Christoph C Hofmann Maike M Breithaupt Angele A Genc Nafiye N Stadelmann Christine C Saez-Rodriguez Julio J Bronsert Peter P Knobeloch Klaus-Peter KP Blank Thomas T Thimme Robert R Glatzel Markus M Prinz Marco M Bengsch Bertram B

Immunity 20210609 7

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 centra ...[more]

PMID: 34174183

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Dataset Information

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

Publications

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

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