Fig. 1 HCoVs probably exhibit neuropathological consequences through multiple routes. ① Direct invasion. After invasion, the production and release of virus may induce cell death by several pathways. ② Immune response. The virus can lead to over-activation of host immune response, releasing a large number of pro-inflammatory cytokines and chemokines (e.g., IL-6, IL-1β, IL-2, IL-8, IL-17, G-CSF, GM-CSF, IP10, MCP1, CCL3, and TNF). Cytokine signal pathways will subsequently induce the cell death and tissue damage. ③ Neuroendocrine-immune crosstalk. Aberrant release of neuropeptides from the infected neurons may act at the endocrine glands, such as adrenal gland. These neuropeptides might cause anomalous release of glucocorticoids and other peptides, which may contribute to the dysregulation of immune system