Fig. 3: A neuroinflammatory COVID-19 milieu marked by disease-associated microglia.
From: Dysregulation of brain and choroid plexus cell types in severe COVID-19
a, UMAP of immune cells captured in the human frontal cortex, split by control individuals (including a patient with influenza) (n = 8) (red) and patients with COVID-19 (n = 8) (light blue). Cells are coloured by cell-type subcluster (red cluster defined by homeostatic markers; light blue cluster defined by activation markers). b, Quantification of immune cell cluster 1 as a proportion of total immune cells (n = 8 control individuals (including a patient with influenza (circle marked as ‘flu’)); n = 8 patients with COVID-19, two-sided Mann–Whitney t-test P = 0.0098; mean ± s.e.m.). c, As in b, but for T cells. P = 0.0003. d, e, As in a, b, respectively, but for MRC1− parenchymal microglia. P = 0.0343. Unlike macrophages, microglia express low levels of MRC1 (CD206)34. Examples of genes that are upregulated in the microglial cluster associated with COVID-19 are shown in light blue. f, Pseudotime trajectory (Methods) indicated in graded purple (low) to yellow (high), plotting the emergence of the microglial cluster associated with COVID-19. Numbers indicate original source population (1) and the newly emerged population in COVID-19 (2). g, Immunohistochemical staining for the microglial activation marker CD68 (brown) in the frontal medial cortex of a patient with COVID-19, immediately adjacent to that used for snRNA-seq. Haematoxylin counterstain (blue). Scale bars, 20 μm. Immunohistochemical stains are representative of at least two independent experiments. h, Overlap (hypergeometric test) between marker genes of Alzheimer’s-disease-associated microglia (DAM, ARM and Mic1)4,5,6 and genes that are upregulated in the microglial cluster associated with COVID-19.
