Sex-specific microglial response following SARS-CoV-2 infection. (a) Representative histological stainings of Iba1+ myeloid cells at a 10× widefield magnification from cinglulate cortex of female (i-iv) and male (v-viii) animals with PBS or SARS-CoV-2 infection at 6 and 21 dpi. Right images are zoomed in versions of the left images. Scale bar = 200 μm for overview images and 50 μm for inset close-up images. The viridis lookup table was used for the histological images in the inset to increase the visibility of intensity differences. The overview images are depicted using a gray LUT to increase visibility of cell morphology. (b) Heatmaps of group mean normalized Iba1+ cell densities per brain region in female and male animals in the three groups (PBS, 6 dpi and 21 dpi). (c–j) Quantification of mean Iba1+ cell densities (normalized to female and male PBS mean) in relevant regions. Bars represent mean ± SEM, circles depict individual animals. Red: female, green: male. Mark the different scales on the y-axes. Statistics: Two-way ANOVA analysis of Iba1+ cells across sex and brain regions followed by Šídák's multiple comparisons test (PBS vs 6 dpi and PBS vs 21 dpi for each sex). Further information on 2way ANOVA statistics and sample sizes can be found in Supplementary data file 1. (p < 0.05, ∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001. No outliers excluded.