Extended Data Fig. 11 ∣. Activation of parenchymal microglia and perivascular macrophages in COVID-19.

Immunohistochemical staining of microglia and macrophages by an antibody against the pro-inflammatory marker CD68⁸⁸ (immunoreaction in brown). Counterstained with haematoxylin for cell nuclei in blue. a, The frontal medial gyrus of patients with COVID-19 immediately adjacent to that used for snRNA-seq. A cluster of activated microglia up to single macrophages is immunostained in the parenchyma of the gyrus (subcortical white matter). Scale bar, 20 μm. b, A vessel of the medial frontal gyrus is surrounded by activated perivascular macrophages. Scale bar, 20 μm. c, The cortical surface is shown. The upper third of the figure contains the leptomeninges that cover the cortex. A dense infiltration by brown stained macrophages into the leptomeninges is visible. Scale bar, 20 μm. d, Summary of innate immune reactivity across eight patients with COVID-19, typically not observed in healthy brains at these levels, colour-coded and labelled by severity. A semiquantitative categorization for changes, as usual in the field of pathology, is used: mild = detectable microgliosis, atypical for healthy tissue; moderate = a pathological process typical of pathological changes; severe = a marked pathological process. Several clusters of microglia or macrophages were characterized as excessive beyond the severe category. Immunohistochemical stains are representative of at least two independent experiments.