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:
- 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).
- The virus affects cerebral blood vessels and causes coagulopathy
(33-35).
- 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.)