Fig. 5: Double label TMEM119 (microglia marker, red)/CD68 (lysosomal activity marker, green) fluorescent immunohistochemistry in COVID-19 and control subjects.

a, b In COVID-19, microglial cells present a distinctly activated phenotype whilst maintaining homeostatic microglial marker TMEM119 (red) and displaying increased lysosomal activity (CD68, green). Arrows indicate CD68+/TMEM119− monocyte/macrophage in the parenchyma. c, d In control subjects, TMEM119 marks both the soma and sparse ramifications of resident microglia, suggesting less prominent activation without significant marker downregulation. CD68 immunoreactivity (green) is also present, but not as distributed as in COVID-19. e Welch one-way ANOVA of CD68+ A% in COVID-19 and controls reveals statistically significant differences between the two groups at the level of the medulla (p < 0.0001) and midbrain (p < 0.0001), but not the pons. The box plots boundaries represent, from the bottom to the top, the 25th percentile (lower box boundary), the median (central line) and 75th percentile (upper box boundary); whiskers represent the minimum and maximum values. f Spearman correlation between microglial densities across brainstem levels and hospitalization time reveals a statistically significant positive correlation between medullary microgliosis and hospitalization time (r = 0.44; p = 0.044).