COVID-19 from a cardiovascular perspective / COVID-19 desde una perspectiva cardiovascular

Currently, myocardial injury has been reported in patients hospitalized with coronavirus disease 2019 (COVID-19). The studies also show a correlation between cardiac events and severe forms of the disease. COVID-19 begins with an early infection phase in which the virus infiltrates the lung parenchyma and proliferates. It then progresses to the pulmonary phase, where the initial inflammatory process, characterized by vasodilation, vascular permeability, and leukocyte recruitment, leads to lung damage, hypoxemia, and cardiovascular stress. The renin angiotensin aldosterone system is important in the pathophysiology of severe acute respiratory syndrome coronavirus 2 infection and in the propagation of systemic inflammation. Within this system, the pathway mediated by angiotensin-converting enzyme 2 (ACE2) produces vasodilation, cardioprotection, anti-oxidation, and anti-inflammation. Furthermore, the free form of ECA2 prevents binding of the virus to host cells and reduces its damage to the lung.

Actualmente, se ha reportado injuria miocárdica en pacientes hospitalizados por enfermedad por coronavirus 2019 (COVID-19). Los estudios, además, demuestran una correlación entre los eventos cardiacos y formas severas de la enfermedad. La COVID-19 comienza con una fase de infección temprana en la que el virus infiltra el parénquima pulmonar y prolifera. Luego progresa a la fase pulmonar, donde el proceso inflamatorio inicial, caracterizado por vasodilatación, permeabilidad vascular y reclutamiento de leucocitos, lleva a daño pulmonar, hipoxemia y estrés cardiovascular. El sistema renina angiotensina aldosterona es importante en la fisiopatología de la infección por el coronavirus 2 del síndrome respiratorio agudo grave y en la propagación de la inflamación sistémica. Dentro de este sistema, la vía mediada por la enzima convertidora de angiotensina 2 (ECA2) produce vasodilatación, cardioprotección, antioxidación y antiinflamación. Además, la forma libre de la ECA2 previene la unión del virus a las células huésped y reduce su daño al pulmón.

Potential use of renin-angiotensin-aldosterone system inhibitors to reduce COVID-19 severity.

SARS-CoV-2 infection and its clinical manifestations (COVID-19) quickly evolved to a pandemic and a global public health emergency. The limited effectivity of available treatments aimed at reducing virus replication and the lessons learned from other coronavirus infections (SARS-CoV-1 or NL63) that share the internalization process of SARS-CoV-2, led us to revisit the COVID-19 pathogenesis and potential treatments. Virus protein S binds to the angiotensin-converting enzyme 2 (ACE2) initiating the internalization process. Endosome formation removes ACE2 from the cellular membrane preventing its counter-regulative effect mediated by the metabolism of angiotensin II to angiotensin (1-7). Internalized virus-ACE2 complexes have been identified for these coronaviruses. SARS-CoV-2 presents the highest affinity for ACE2 and produces the most severe symptoms. Assuming ACE2 internalization is the trigger for COVID-19 pathogenesis, accumulation of angiotensin II can be viewed as the potential cause of symptoms. Angiotensin II is a strong vasoconstrictor, but has also important roles in hypertrophy, inflammation, remodeling, and apoptosis. Higher levels of ACE2 in the lungs explain the acute respiratory distress syndrome as primary symptoms. Most of the described findings and clinical manifestations of COVID-19, including increased interleukin levels, endothelial inflammation, hypercoagulability, myocarditis, dysgeusia, inflammatory neuropathies, epileptic seizures and memory disorders can be explained by excessive angiotensin II levels. Several meta-analyses have demonstrated that previous use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were associated with better prognosis for COVID-19. Therefore, pragmatic trials to assess the potential therapeutic benefits of renin-angiotensin-aldosterone system inhibitors should be urgently promoted by health authorities to widen the therapeutic options for COVID-19.

Renin-angiotensin system: Basic and clinical aspects-A general perspective.

The renin-angiotensin system (RAS) is one of the most complex hormonal regulatory systems, involving several organs that interact to regulate multiple body functions. The study of this system initially focused on investigating its role in the regulation of both cardiovascular function and related pathologies. From this approach, pharmacological strategies were developed for the treatment of cardiovascular diseases. However, new findings in recent decades have suggested that the RAS is much more complex and comprises two subsystems, the classic RAS and an alternative RAS, with antagonistic effects that are usually in equilibrium. The classic system is involved in pathologies where inflammatory, hypertrophic and fibrotic phenomena are common and is related to the development of chronic diseases that affect various body systems. This understanding has been reinforced by the evidence that local renin-angiotensin systems exist in many tissue types and by the role of the RAS in the spread and severity of COVID-19 infection, where it was discovered that viral entry into cells of the respiratory system is accomplished through binding to angiotensin-converting enzyme 2, which is present in the alveolar epithelium and is overexpressed in patients with chronic cardiometabolic diseases. In this narrative review, preclinical and clinical aspects of the RAS are presented and topics for future research are discussed some aspects are raised that should be clarified in the future and that call for further investigation of this system.

Overexpression of the Severe Acute Respiratory Syndrome Coronavirus-2 Receptor, Angiotensin-Converting Enzyme 2, in Diabetic Kidney Disease: Implications for Kidney Injury in Novel Coronavirus Disease 2019.

OBJECTIVES: Diabetes is associated with adverse outcomes, including death, after coronavirus disease 19 (COVID-19) infection. Beyond the lungs, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the etiologic agent of the COVID-19 pandemic, can infect a range of other tissues, including the kidney, potentially contributing to acute kidney injury in those with severe disease. We hypothesized that the renal abundance of angiotensin-converting enzyme (ACE) 2, the cell surface receptor for SARS-CoV-2, may be modulated by diabetes and agents that block the renin-angiotensin-aldosterone system (RAAS). METHODS: The expression of ACE 2 was examined in 49 archival kidney biopsies from patients with diabetic kidney disease and from 12 healthy, potential living allograft donors using next-generation sequencing technology (RNA Seq). RESULTS: Mean ACE 2 messenger RNA was increased approximately 2-fold in diabetes when compared with healthy control subjects (mean ± SD, 13.2±7.9 vs 7.7±3.6 reads per million reads, respectively; p=0.001). No difference in transcript abundance was noted between recipients and nonrecipients of agents that block the RAAS (12.2±6.7 vs 16.2±10.7 reads per million reads, respectively; p=0.25). CONCLUSIONS: Increased ACE 2 messenger RNA in the diabetic kidney may increase the risk and/or severity of kidney infection with SARS-CoV-2 in the setting of COVID-19 disease. Further studies are needed to ascertain whether this diabetes-related overexpression is generalizable to other tissues, most notably the lungs.