Key result
SARS-CoV-2 drives multi-organ pathology primarily via ACE2 receptors, though expression alone fails to explain clinical variability.
Why the study?
The variability in clinical presentation and prognosis of COVID-19 due to SARS-CoV-2 molecular pathways and ACE2 receptor involvement has not been clarified.
This review highlights the complex molecular pathways, including ACE2 downregulation and renin-angiotensin system dysregulation, that contribute to the multi-organ pathology and clinical variability of COVID-19.
ACE2 variability may underlie COVID-19 clinical heterogeneity; leaves open targeted interventions until prospective trials validate.
OBJECTIVE: In human pathology, SARS-CoV-2 utilizes multiple molecular pathways to determine structural and biochemical changes within the different organs and cell types. The clinical picture of patients with COVID-19 is characterized by a very large spectrum. The reason for this variability has not been clarified yet, causing the inability to make a prognosis on the evolution of the disease. MATERIALS AND METHODS: PubMed search was performed focusing on the role of ACE 2 receptors in allowing the viral entry into cells, the role of ACE 2 downregulation in triggering the tissue pathology or in accelerating previous disease states, the role of increased levels of Angiotensin II in determining endothelial dysfunction and the enhanced vascular permeability, the role of the dysregulation of the renin angiotensin system in COVID-19 and the role of cytokine storm. RESULTS: The pathological changes induced by SARS-CoV-2 infection in the different organs, the correlations between the single cell types targeted by the virus in the different human organs and the clinical consequences, COVID-19 chronic pathologies in liver fibrosis, cardiac fibrosis and atrial arrhythmias, glomerulosclerosis and pulmonary fibrosis, due to the systemic fibroblast activation induced by angiotensin II are discussed. CONCLUSIONS: The main pathways involved showed different pathological changes in multiple tissues and the different clinical presentations. Even if ACE2 is the main receptor of SARS-CoV-2 and the main entry point into cells for the virus, ACE2 expression does not always explain the observed marked inter-individual variability in clinical presentation and outcome, evidencing the complexity of this disorder. The proper interpretation of the growing data available might allow to better classifying COVID-19 in human pathology.
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L. et al. (2020) conducted a review in COVID-19. SARS-CoV-2 infection was evaluated. SARS-CoV-2 utilizes multiple molecular pathways, primarily via ACE2 receptors, to induce pathological changes across different organs, though ACE2 expression alone does not explain clinical variability.
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