Fig. 1.

Infection with the SARS-CoV-2 virus may lead to brain pathology through potential direct and indirect mechanisms. SARS-CoV-2 infection leads to cytokine storms. Recent evidence suggests that interleukin (IL)-1ra, IL-6, Monocyte Chemoattractant Protein (MCP)-3, and serum interferon gammainduced protein (IP)-10 are implicated in the fatal outcomes of COVID-19 infection [81, 86]. Cytokine storms can damage an intact blood–brain barrier and disrupt normal functioning in the CNS without the virus crossing the blood–brain barrier from the systemic circulation. In addition, COVID-19 has been associated with a pro-thrombotic state, which may lead to occlusion of cerebral vessels and lead to brain injury [81]. Finally, ACE2, a functional receptor of SARS-CoV-2, may facilitate direct invasion of neurons and cerebrovascular endothelial cells, leading to apoptosis and necrosis of neurons and neighboring cells [64]. Original figure created by Nicole J. Katchur