Universitätsklinikum Freiburg, Freiburg, Germany
Imaging Session: Wednesday, September, 29th, 2021, 12:00pm – 1:30pm
Spatial single-cell mapping reveals an altered local immune response in COVID-19 brains
COVID-19 can cause acute and chronic neurological symptoms, but the underlying immune pathophysiological mechanisms, including the involved immune cells and viral tropism in the central nervous system (CNS) are unclear. Therefore we analyzed postmortem tissue of the brain stem and olfactory bulb from COVID-19 patients and additional healthy and non-COVID-19 controls at a spatially-resolved, high-dimensional single-cell level.
We utilized Imaging Mass Cytometry (IMC) with subsequent bioinformatic analysis to deeply profile the involved immune cells, their spatial distribution and interactions as well as viral antigen expression in the brain. Our findings were contextualized and validated using chromogenic and fluorescent immunohistochemistry, other histological staining methods and mass cytometry.
We observed substantial immune activation in the CNS of COVID-19 patients compared to controls and identified distinct phenotypes of T cells and microglial cells, their presence in specific anatomical regions and context-specific cellular interactions. Accumulations of activated microglia cells, termed microglial nodules, and the perivascular space constituted key sites of the local immune response, enriched for CD8+ T cells and representing areas of COVID-19 specific cellular interactions compared to our controls. Moreover, viral antigen was present in ACE2-expressing cells in the vascular compartment representing a possible foundation for the broad immune activation and a potential port of entry for SARS-CoV-2 into the CNS. Interestingly, COVID-19 related neuroinflammation was associated with severe axonal damage, blood-brain barrier leakage and astrogliosis providing a structural basis for transitory and long-lasting neurologic deficits. Finally, blood CRP and PTT levels correlated with CD8 T cell infiltration suggesting a link between neuroinflammation and a systemic procoagulant state, a hallmark of severe COVID-19.