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.