Table 1.
SARS- COV2 activated signaling pathways and Pathophysiological effects in various organs.
| Affected organ | Clinical features | Involved receptors or signaling path ways or cytokine | Pathophysiological effects |
|---|---|---|---|
| Respiratory system | cough, pneumonia, hypoxia low level of blood oxygen Shortness of breath | CD4 cytokine receptors, TLRs, and T-cell receptors IKKa and IKKb, p50 and p65, NF-κB subunits MAPK/ERK, GPCRs DLK, ASK, MKK3 and MKK6, ATF1/2/6, p53, SOCS-1 JAKs | alveolar lesion, alveolar edema, ground-glass opacities, diffuse bilateral infiltration, respiratory failure |
| gastrointestinal (GI) symptoms | stomach discomfort, anorexia, lack of appetite,vomiting, nausea, diarrhea, melena, constipation, haematochezia, upper GI bleeding, and acid reflux (Zhong et al., 2020). | TMPRSS2, ACE2 and RAS NF-κB and p38 mitogen kinase, pathways. IL-8, IL-6, IL-1, TNF-α MIP1α, MCP1, IP10, GM-CSF, IL-10, IL-7, and IL-2. | primary GI damage and Secondary GI damage. Disruption of the intestinal barrier integrity, The gut microbiota alteration, Systemic immune reaction and inflammation |
| Cardiovascular system | myocarditis, acute coronary syndrome (ACS), hypertension, cardiac arrhythmia, cardiac arrest, acute myocardial infarction (AMI), elevated serum creatinine, venous thromboembolic disease, increase in cardiac troponin I, decreased systolic function, decreased cardiac contractility strength, producing inotropic deficit, increased filling pressures, ventricular dysfunction, myocardial edema, reduced ventricular ejection fraction, ST-segment elevation, depression of ST segment and inverted T wave in V1 and a VR lead | ACE2 and its receptors in heart, MiRNAs,IL-4, IL-10, IL-6 | diffuse edema in myocardium and interstitial space, hypokinesia, myocardial thickening, macrophage infiltration, coronary vasospasm, microthrombi, activated macrophages, collagen degradation, Endotheliitis, infiltration of inflammatory cells, apoptotic bodies, imbalance of oxygen supply |
| Kidney | AKI, renal infarction proteinuria, hematuria | ACE2 and its receptors in kidney epithelial, IL6, IL-1, and TNF- alpha | Cytokine storm acute tubular necrosis (ATN), tubulointerstitial necrosis (TIN), collapsing glomerulopathy Glomerular lesions |
| Nervous system | Headache | Inflammatory cytokines that are involved in the fever process and ACE2 receptor | Increase in cytokine storms |
| Nervous system | Impaired Consciousness | viral encephalitis, septic encephalopathy, metabolic perturbations, stroke | reflect the disease severity |
| Nervous system specially the brain stem | Agitation and Delirium | Activation of CNS inflammatory mediators | secondary effect of other organ system failure |
| Nervous system specially olfactory dysfunction and gustatory dysfunction | Hypogeusia/Dysgeusia and Hyposmia/Anosmia | viral attachment to ACE2 receptors in endothelium causing widespread endotheliitis that is associated to the cytokine storm | Loss of smell may be caused by axonal movement of SARS-CoV-2 into the brain via the cribriform plate |
| Nervous system | Seizures | electrolyte derangements, hypoxia, organ failure | rhythmic discharges or arhythmies |
| Nervous system | meningitis | Increase in inflammatory cytokine activation | Lethargy and unconsciousness |
| Nervous system | Encephalopathy | Associated with cytokine-mediated brain injury | high inflammatory response |
| Nervous system | mood disorders | RAS mechanisms | Unknown exact mechanism |
| Nervous system | cerebrovascular diseases | RAS mechanisms | Decrease in blood pressure |
Signaling pathways activated by SARS-CoV2, clinical features, pathophysiological effects in various organs. Abbreviations: (RAS, renin-angiotensin systems; NF-κB, nuclear factor-κB, AMI, acute myocardial infarction; TNF-α, tumor necrosis factor –α)