SARS-CoV-2, ACE2 expression, and systemic organ invasion

Abstract

A novel coronavirus disease, COVID-19, has created a global pandemic in 2020, posing an enormous challenge to healthcare systems and affected communities. COVID-19 is caused by Severe Acute Respiratory Syndrome (SARS)-CoronaVirus-2 (CoV-2) that manifests as bronchitis, pneumonia, or a severe respiratory illness. SARS-CoV-2 infects human cells via binding a "spike" protein on its surface to angiotensin-converting enzyme 2 (ACE2) within the host. ACE2 is crucial for maintaining tissue homeostasis and negatively regulates the renin-angiotensin-aldosterone system (RAAS) in the humans. The RAAS is paramount for normal function in multiple organ systems including the lungs, heart, kidney, and vasculature. Given that SARS-CoV-2 internalizes via ACE2, the resultant disruption in ACE2 expression can lead to altered tissue function and exacerbate chronic diseases. The widespread distribution and expression of ACE2 across multiple organs is critical to our understanding of the varied clinical outcomes of COVID-19. This perspective review based on the current literature was prompted to show how disruption of ACE2 by SARS-CoV-2 can affect different organ systems.

Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review

“…It is suggested that classifying ACE2 organ distribution could be useful to understand SARS-CoV-2 pathogenesis [ 9 ]. ACE2 expression was detected in various organs such as the heart, lung, kidneys, oral cavity, brain, pancreas, gastrointestinal tract and brain [ 7 ]. Therefore, it is likely that organ vulnerability and severity of pathology depend on the level of ACE2 gene expression [ 7 , 9 , 58 ], aligning with the hypothesis that high ACE2 levels have been detected in both lungs and heart [ 9 , 16 , 59 ].…”

“…ACE2 expression was detected in various organs such as the heart, lung, kidneys, oral cavity, brain, pancreas, gastrointestinal tract and brain [ 7 ]. Therefore, it is likely that organ vulnerability and severity of pathology depend on the level of ACE2 gene expression [ 7 , 9 , 58 ], aligning with the hypothesis that high ACE2 levels have been detected in both lungs and heart [ 9 , 16 , 59 ]. In addition, alveolar epithelial type II cells and cardiomyocytes (mostly aged ones) have high expression of genes that positively regulate viral reproduction and transmission thus, consistently with lung and heart vulnerability [ 22 , 60 ].…”

“…The pathogenesis of COVID-19 has two stages [ 5 , 6 , 7 ]: the first one, where SARS-CoV-2 replicates and patients manifest a range of non-specific symptoms (e.g., fever, muscle aches, shortness of breath, headache, sore throat and gastrointestinal discomfort) [ 3 , 6 ]. The second stage is characterized by an adaptive immune response with humoral, cellular and cytokine responses manifesting in a large range of clinical presentations [ 6 ].…”

“…Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for SARS-CoV-2, which is the cause of COVID-19 in humans. ACE2 is a type I transmembrane metallocarboxypeptidase expressed in endothelial cells, alveolar type 2 lung epithelial cells, renal tubular epithelium, Leydig cells in the testes, and gastrointestinal tract [ 7 ]. ACE2 mediates the interaction between host cells and SARS-CoV-2 spike (S) protein [ 8 ].…”

The post-acute phase of SARS-CoV-2 infection in two macaques species is associated with signs of ongoing virus replication and pathology in pulmonary and extrapulmonary tissues

“…J16012 and Ji408005 were only positive in respiratory tract tissues, Ji408005 tested positive in the pharyngeal mucosa, lung and two lung lymph nodes, while viral RNA was detected in the carinal part of the trachea, lung and four lung lymph nodes of animal J16012. In the two other PCR-positive macaques (R14002 and J16017), RNA was detected in the respiratory system and the tracheobronchial lymph nodes, but also in cervical and mesenteric lymph nodes, skin, conjunctiva, liver, spleen, kidney, salivary gland and heart, all organs and tissues that have been described as target tissues in humans [58]. High viral RNA loads were measured in some lymph nodes of these animals, ranging from 2 x 10 5 to 1 x 10 6 GE/gram of tissue.…”