Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T cell interactions, 2021

rvallee

rvallee

Senior Member (Voting Rights)
  • Performed detailed molecular and spatial analysis of the COVID-19 brain immune response
  • Pathognomonic microglial nodules and T cell infiltration are present in COVID-19 brains
  • Altered microglia-T cell interactions correlate with systemic measures of inflammation
  • Vascular leakage is linked with immune activation, ACE2 expression and viral antigen
COVID-19 can cause severe neurological symptoms, but the underlying pathophysiological mechanisms are unclear. Here, we interrogated the brain stem and olfactory bulb in COVID-19 patients postmortem 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, 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.


https://www.cell.com/immunity/fulltext/S1074-7613(21)00246-6
 
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