Pathogenesis of SARS CoV-2
The SARS CoV-2 virus enters the body through the respiratory epithelial
cells. The envelope spike protein (S protein) engages with the ACE2
receptors on epithelial cells.2 This fusion can either
be mediated by an early pathway (involving the serine protease TMPRSS2)
or an endocytic late pathway (involving the cathepsin B/L
pathway).4 Viral replication and release probably lead
to a period of viremia. This is evidenced by viral RNA being detected in
the stool and urine of humans.5 Macaque autopsy
studies have shown viral particle staining in the lungs, lymph nodes,
and ileum, suggesting interaction with these cells.6Replication increases viral load and is known to downregulate the ACE2
receptor.7
Longer duration of viral shedding has been noticed in older monkeys than
younger ones.6 This might indicate a delayed immune
response in older individuals to viral invasion. A delayed response
could lead to greater ACE2 downregulation making older individuals
susceptible to reaching a critical or tipping point in the pathogenesis.