Fig. 2: cGAS–STING-dependent type I IFN signature in COVID-19 skin and lung pathology.

a, Confocal microscopy images of a representative COVID-19 skin sample stained for CD163 (green), IFNB1 mRNA (red) and DNA (blue). Scale bars, 10 μm. Arrows indicate cytosolic DNA particles. b, Quantification of CD163⁺ macrophages containing cytosolic DNA particles in COVID-19 skin lesions (n = 10) and in healthy skin (n = 9). c, Quantification of cGAMP in lysates of COVID-19 skin lesions (n = 10) and healthy skin (n = 3). d, Confocal microscopy images of a representative COVID-19 skin sample stained for CD163 (green) and p-STING (red). Blood vessels, dashed line. Arrows show p-STING⁺ endothelial cells. Scale bars, 20 μm (left); 5 μm (right two images). e, Quantification of p-STING⁺ macrophages in COVID-19 skin lesions (n = 10) and in healthy skin (n = 10). f, Confocal microscopy images of a representative COVID-19 skin sample stained for CD31 (green) and p-STING (red). Blood vessels, dashed line. Scale bars, 20 μm. g, Proportions of CD163⁺ macrophages and CD31⁺ endothelial cells among p-STING⁺ cells in COVID-19 skin lesions (n = 7). h, Expression of ISGs (IFI35, IRF7 and MX1) in cultured healthy skin (n = 3) and COVID-19 skin explants (n = 3), treated or not with H-151. i, Confocal microscopy images of representative post-mortem lungs with early (fewer than 10 days; left) or late (more than 14 days, right) DAD, stained for p-STING (red) and CD163 (green). Scale bars (left to right): 20 μm, 10 μm, 50 μm, 10 μm. j, Quantification of p-STING⁺CD163⁺ macrophages in post-mortem lungs with early and late DAD (n = 4). k, Immunohistochemistry of representative post-mortem lungs with early (left) or late (right) DAD, stained for MxA. Scale bar, 50 μm. l, Percentage of tissue area with MxA positivity in early and late DAD samples (n = 4). Data are mean ± s.d. (b, c, e, h, j, l). P values obtained with two-tailed Student’s t-test (c, e, h, j, l) and with Mann–Whitney test (b).

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