Fig. 1

Microglia is a central player in the pathological events developing in the brain of COVID-19-infected patients. The infection-induced injury takes place preferentially in the medulla oblongata with its cardiovascular and respiratory centers whose disturbance may lead to severe danger for life. Microglial cells project their cytoplasmic processes to blood vessels and cause disintegration of vascular endothelium. They also project to the blood-brain-barrier (BBB), and by causing its breakdown, allow the entry of monocytes/macrophages into the cerebrospinal fluid (CSF). Eventually, microglia send their projections to glutamatergic neurons and engulf synaptic terminals/axons initiating the disintegration of the myelin sheath. Microglia are endowed with a number of receptors. The G protein (G)-coupled typical 7 transmembrane region P2Y12 receptor (R) senses ADP, which is generated by enzymatic degradation of extracellular ATP, flowing out from neuronal and non- neuronal cells through their damaged cell membrane. The P2Y12R induces the elongation of microglial processes to the sites of injury and later the migration of activated, ameboid microglia to these sites. COVID infection decreases the density of P2Y12Rs interfering with the recognition of ADP and thereby with the defensive microglial functions. The ligand-gated P2X7R is a cationic channel (permeable to Na⁺, K⁺ and Ca²⁺) which binds millimolar concentration of ATP; the loss of intracellular K⁺ is the first step in activating the NLRP3 inflammasome. In co- operation with the toll-like receptor 3 (TLR3) responding to e.g., the bacterial endotoxin lipopolysaccharide (LPS), or in the case of COVID-disease, virus particles, the activation of the proteolytic enzyme caspase-1 ensues. This results in the production and release of the pro-inflammatory cytokine interleukin-1 (IL-1). IL-6 also joins IL-1 to promote neuroinflammation. The G protein-coupled 7 transmembrane region chemokine receptor CX3CR1 (fractalkine-R) is stimulated by CX3CL1, released from neurons. The microglial mitochondria contain lowered levels of cytochrom c (Cytc) as a consequence of its outflow into the cytoplasm as a marker of apoptosis. Microglia phagocytose viruses; phagolysosomes arise by the fusion of phagosomes and lysosomes containing the virus, and myelin basic protein from the disintegrated myelin sheath of neuronal axons