Fig. 4

Neuron and myelin sheath damage associated with abnormal protein expression in COVID-19 brains. a Cerebral neurons show various degrees of damage, including red degeneration of neurons, dissolution and disappearance of Nissl bodies, and formation of giant neurons in gray matter. b The number of cerebellar Purkinje and granular cells was decreased and their dendrites and axons show injured. c Loose and rupture of white matter. d Electron microscopic examination shows the swollen axons and myelin sheath (scale bars 2 μm). e Functional pathway enrichment analysis of differentially expressed proteins in brain tissues from patients with COVID-19 vs. controls. Blue bars represent the −log₁₀ p-value of the downregulated functional categories with COVID-19 vs. controls. Columns on the left of the heatmap represent different function categories. The right of the heatmap represents the gene names. Red and blue boxes indicate normalized intensity of the enriched or depleted proteins, respectively. Histogram showing the ratio of protein intensities from COVID-19 brains compared to control brains. Y-axis represents the log₂ COVID-19/controls. f Interaction network of proteins differentially expressed in brains of patients with COVID-19 vs. controls. The primary biological process analyses include a map of functional categories. Red circles represent proteins with high expression in brain tissue from patients diagnosed with COVID-19 compared to controls. Color gradient indicates the protein abundance levels in the brains of COVID-19 patients