SARS-CoV-2 is transmitted predominantly via respiratory droplet, contact, and potential in fecal-oral
Primary viral replication is presumed to occur in mucosal epithelium of upper respiratory tract
It further multiplies in the lower respiratory tract and gastrointestinal mucosa giving rise to a mild viremia
Some patients have also exhibited non-respiratory symptoms such as acute liver and heart injury, kidney failure, diarrhea implying multiple organ involvement
ACE2 is broadly expressed in nasal mucosa, bronchus, lung, heart, esophagus, kidney, stomach, bladder, and ileum, and these human organs are all vulnerable to SARS-CoV-2
Pathological findings
The pathological findings from a severe COVID-19 showed pulmonary bilateral diffuse alveolar damage with cellular fibromyxoid exudates
The right and left lungs both showed acute respiratory distress syndroms (ARDS)
Interstitial mononuclear inflammatory infiltrates, dominated by lymphocytes, could be observed in both lungs
These pulmonary pathological findings extremely resemble those seen in SARS and MERS
Only a few interstitial mononuclear inflammatory infiltrates were found in the heart tissue, which means that SARS-CoV-2 might not directly impair the heart
Massive mucus secretion in both lungs was found in death cases with COVID-19
Acute respiratory distress syndrome
ARDS is a life-threatening lung condition that prevents enough oxygen from getting to the lungs and into the circulation
In fatal cases of human SARS-CoV-2 infections individuals exhibit severe respiratory distress requiring mechanical ventilation
Increased levels of plasma IL-6 and IL-8 and genes ACE2, interleukin 10 (IL-10), tumor necrosis factor (TNF), and vascular endothelial growth factor (VEGF) are associated with the development or outcome of ARDS
Cytokine storm
Clinical findings showed exuberant inflammatory responses during SARS-CoV-2 infection resulting in uncontrolled pulmonary inflammation, which is a leading cause of case fatality
The initial onset of rapid viral replication may cause massive epithelial and endothelial cell death and vascular leakage, triggering the production of exuberant pro-inflammatory cytokines and chemokines
Loss of pulmonary ACE2 function causes acute lung injury leading to dysfunction of the renin-angiotensin system (RAS) resulting in enhanced inflammation and vascular permeability
Immune dysfunction
High concentrations of proinflammatory CD4 T cells and cytotoxic granules CD8 T cells were observed in sever cases, suggesting antiviral immune responses and overactivation of T cells
