Spatial single-cell mapping reveals an altered local immune response in COVID-19 brains
COVID-19 causes neurological symptoms that can be potentially life-threatening in up to 67 % of the patients. To understand the local immune response during SARS-CoV-2 infection at a spatially resolved, high-dimensional single-cell level, we performed a 38-biomarker imaging mass cytometry analysis of the brain stem and olfactory bulb from COVID-19 patients and additional controls. Importantly, utilizing an unbiased image segmentation and cell classification pipeline, we observed a significant immune activation in the central nervous system (CNS) and identified novel context-specific CD8 T cell and microglial clusters. Spatially resolved single-cell analysis identified distinct phenotypes of T cells and microglial clusters, their presence in specific anatomical regions and their cellular interactions. The analysis further highlights microglial nodules and perivascular immune cell clusters as key sites of the local immune response in the brain stem. It also demonstrates that disease-associated neuroinflammation is associated with severe axonal damage as a structural basis for neurologic deficits. Finally, IMC staining for SARS-CoV-2 spike glycoprotein revealed direct evidence of vasculature-associated viral presence in the olfactory bulb and brain stem as well as reactive astrogliosis. Together these analyses identify the immune correlates of a surprisingly high level of neuroinflammation in fatal cases of COVID19.
Henrike Salié is performing her doctorate studies in the lab of Prof. Bengsch in the Clinic for Internal Medicine II at the University Medical Center Freiburg. Her research focus is on understanding immune responses to malign, autoimmune and viral challenges in tissues, with a focus on the spatial interactions of exhausted T cells, for which she established an imaging mass cytometry approach. During the SARS-CoV-2 pandemic she explored the neuroinflammation in brains of COVID-19 patients in a collaborative effort with the Institutes of Neuropathology in Freiburg (AG Prinz), Hamburg (AG Glatzel) and Göttingen (AG Stadelmann-Nessler).
COVID-19, Imaging mass cytometry, T cell exhaustion