Abstract
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), was first identified in Eastern Asia (Wuhan, China) in December 2019. The virus then spread to Europe and across all continents where it has led to higher mortality and morbidity, and was declared as a pandemic by the World Health Organization (WHO) in March 2020. Recently, different vaccines have been produced and seem to be more or less effective in protecting from COVID-19. The renin–angiotensin system (RAS), an essential enzymatic cascade involved in maintaining blood pressure and electrolyte balance, is involved in the pathogenicity of COVID-19, since the angiotensin-converting enzyme II (ACE2) acts as the cellular receptor for SARS-CoV-2 in many human tissues and organs. In fact, the viral entrance promotes a downregulation of ACE2 followed by RAS balance dysregulation and an overactivation of the angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis, which is characterized by a strong vasoconstriction and the induction of the profibrotic, proapoptotic and proinflammatory signalizations in the lungs and other organs. This mechanism features a massive cytokine storm, hypercoagulation, an acute respiratory distress syndrome (ARDS) and subsequent multiple organ damage. While all individuals are vulnerable to SARS-CoV-2, the disease outcome and severity differ among people and countries and depend on a dual interaction between the virus and the affected host. Many studies have already pointed out the importance of host genetic polymorphisms (especially in the RAS) as well as other related factors such age, gender, lifestyle and habits and underlying pathologies or comorbidities (diabetes and cardiovascular diseases) that could render individuals at higher risk of infection and pathogenicity. In this review, we explore the correlation between all these risk factors as well as how and why they could account for severe post-COVID-19 complications.
Highlights
Coronaviruses are members of Coronaviridae, a heterogeneous family of enveloped RNA viruses causing respiratory and enteric diseases in humans
The viral entrance promotes a downregulation of angiotensin converting enzyme 2 (ACE2) followed by renin–angiotensin system (RAS) balance dysregulation and an overactivation of the angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis, which is characterized by a strong vasoconstriction and the induction of the profibrotic, proapoptotic and proinflammatory signalizations in the lungs and other organs
Many studies are currently ongoing to understand the molecular mechanisms of COVID-19 cellular invasion, and the cascade activation and/or suppressing action detected among host cells
Summary
Coronaviruses are members of Coronaviridae, a heterogeneous family of enveloped RNA viruses causing respiratory and enteric diseases in humans. SARS-CoV-2 over-activates the RAS by binding to the ACE2 receptor, which normally has the function of degrading Ang II [21]. RAS has been shown to be involved in the pathogenesis of COVID-19, since the causative SARS-CoV-2 virus employs the human ACE2 cell surface protein as a receptor to invade host cells [3,34,35,36]. After binding to the virus, the expression of the ACE2 receptor is downregulated [33] This decrease in ACE2 bioavailability as well as the Ang II-AT1R axis’ up-regulation enhance COVID-19-induced inflammation and pulmonary injury [36], and promote organ injury [33]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
