Fig. 1

SARS-CoV-2 causes damage to the nervous system via 4 possible pathways: (1) direct viral encephalitis which caused by direct damage to brain tissue by SARs-CoV-2 as it enters brain cells through ACE2 receptors and causes inflammation and damage. The S (spike) proteins that cover the surface of the virus bind to ACE2 receptors and facilitate viral entry. Once the S protein binds to ACE2 receptor, TM protease serine 2 (TMPRSS2) located in the host cell membrane further facilitates virus entry by activating the S protein. After the virus has entered the host cell, viral RNA is released and protein cleavage and assembly of replicase-transcriptase lead to transcription and replication of viral genome [39]. (2) Systemic inflammation: SARS-CoV-2 infection elicits cytokine storm in the body which, along with severe sepsis can lead to Hippocampal atrophy. (3) cerebrovascular changes: the viral protein ORF3 and ventilation induced hypoxia activate inflammasome NLRP3 which can lead to increase in inflammatory cytokines especially IL-19 IL-1B which can trigger the inflammatory cascade causing impairment of immune system of the brain leading to deposition of pathological fibrillary tangles in brain tissue, and impatient of cerebral hemostasis and function[40]. (4) peripheral organ damage due to systemic inflammation and direct viral infection via ACE2 receptors and ARDS can lead to long term cognitive decline [36] (Image created with BioRender.com)