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Molecular pathways triggered by COVID-19 in different organs: ACE2 receptor-expressing cells under attack? A review
1Department of Radiology, Azienda Ospedaliero Universitaria (AOU), di Cagliari - Polo di Monserrato, Cagliari, Italy. daniela.fanni@unica.it.
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.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes varied COVID-19 symptoms by impacting multiple molecular pathways. Understanding these pathways is crucial for predicting disease progression and improving patient outcomes.
Area of Science:
- Pathology
- Molecular Biology
- Virology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a wide spectrum of clinical presentations in COVID-19 patients.
- The underlying molecular mechanisms driving this clinical variability remain incompletely understood, hindering accurate prognosis.
Purpose of the Study:
- To investigate the molecular pathways utilized by SARS-CoV-2 to induce pathological changes in various organs.
- To explore the role of the renin-angiotensin system, particularly angiotensin-converting enzyme 2 (ACE2) receptors, in viral entry and subsequent tissue damage.
- To understand the contribution of cytokine storms and angiotensin II dysregulation to COVID-19 pathology and disease severity.
Main Methods:
- A comprehensive literature review was conducted using PubMed.
- Search terms focused on ACE2 receptors, viral entry, ACE2 downregulation, tissue pathology, angiotensin II, endothelial dysfunction, vascular permeability, renin-angiotensin system dysregulation, and cytokine storm in the context of COVID-19.
Main Results:
- SARS-CoV-2 infection induces diverse pathological alterations across multiple organs and cell types.
- ACE2, while the primary viral entry receptor, does not fully explain the significant inter-individual variability in clinical outcomes.
- Angiotensin II-mediated fibroblast activation contributes to chronic pathologies like fibrosis and arrhythmias.
Conclusions:
- The complex interplay of molecular pathways, including but not limited to ACE2, dictates the varied pathological changes and clinical manifestations of COVID-19.
- Further research into these pathways is essential for better classification and management of COVID-19.
- Interpreting the accumulating data on SARS-CoV-2 pathogenesis is key to advancing our understanding of this complex disease.
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