Brain cell damage caused by the SARS-CoV-2 virus: Mechanisms
To entry into cells, the virus binds via its S1 spike protein to angiotensin converting enzyme 2 (ACE2) (19, 20). In human, the ACE2 RNA expression, even though shown chiefly in lung tissues (21), heart, gastrointestinal (GI) system, and kidney (22), has been detected in both brain tissues and cerebrospinal fluid (CSF) (23, 24); thus, the nervous system – both the neurons and glial cells of the brain – can be damaged by COVID-19 infection (25). Incidentally, a blood circulatory pathway has been proposed by which this virus—SARS-CoV-2—directly infects the CNS (26), thereby escalating the permeability of the blood brain barrier (BBB). Explicitly, BBB is vital to maintain CNS homeostasis and to prevent the neurons against the penetration of pathogens, such as bacteria and viruses (27).
The exact pathophysiological mechanisms the SARS-CoV-2 virus leads to the neurological adverse symptoms is still not clear. However, some neurotoxic mechanisms rooted from COVID-19 infection have been stated, most noticeable of which will be cited as follows:
  1. The virus is neurotropic and enters into both neurons and glial cells. Also, the virus reaches indirectly the CNS via the BBB and/or directly through olfactory receptors neuron situated in axons thereof, thus neuronal dysfunction and damage – neuro invasion (28-32).
  2. The virus affects cerebral blood vessels and causes coagulopathy (33-35).
  3. The virus can cause a huge releasing proinflammatory cytokines so-called “cytokine storm” and peripheral organs dysfunction relating to the brain (36, 37). All these mechanisms have remarkable role to play in the cognitive impairment etiology in COVID-19 survivors (38). (Figure 1.)