IMMUNE STATUS AND CYTOKINE SPECTRUM AS PREDICTORS OF THE RISK OF SEVERE DISEASE AND PERFORMANCE INDICATORS OF INTENSIVE THERAPY IN PATIENTS WITH CORONAVIRUS INFECTION COVID-19

The pandemic caused by a new strain of the SARS-CoV-2 coronavirus has swept the whole world but effective methods for treating this severe pathology have not yet been created. It has now been established that a risk of a severe course of COVID-19 is not so much a patient's age itself, but so-called age-related diseases;the renin-angiotensin system (RAS) is directly or indirectly involved into their development. The SARS-CoV-19 virus interacts with one of the main regulatory elements of this system, ACE2, and disrupts the balance between the two RAS branches. This ultimately manifests itself in an increase in levels of angiotensin II, which, through binding to the angiotensin type 1 receptor (AT1R), causes a number of pathological conditions, including hypertension, atherosclerosis, and cardiovascular diseases, enhances cell proliferation, apoptosis, death of vascular endothelial cells, etc. This process has been described in many reviews by Russian and foreign authors. However, cells of innate and adaptive immunity are another less well-described but no less important target of angiotensin II. The consequences of this interaction are analyzed in detail in this review. With COVID-19, dendritic cells are activated, macrophage proliferation and neutrophil infiltration increase with further involvement of CD4-lymphocytes and other cellular elements of the adaptive immunity in this process. Hyperactivation of the immune system is accompanied with the release of a large amount of pro-inflammatory cytokines, which can lead to the occurrence of a cytokine storm. The picture is aggravated by the inhibitory effect produced by the virus itself on the synthesis of signaling interferons at initial stages in its internalization into the cell. A separate section in the review addresses the problem how to predict a risk of a developing serious condition and search for its predictors by analyzing the state of the RAS and ratios of key cellular elements in the immune system. This is extremely important for making decisions concerning the amount of necessary medical care and strategies for subsequent treatment. © Sadykov V.F., Poltavtseva R.A., Chaplygina A.V., Bobkova N.V., 2022

The Significance of Angiotensin-Converting Enzyme-2 (ACE2) in SARS-Cov-2 Infection and COVID-19

The new coronavirus was first reported in 2019 (China) and officially announced by the World Health Organization as a pandemic in March 2020. Severe acute respiratory syndrome coro-navirus 2 (SARS-CoV-2) is the causative agent of the pneumonia-associated illnesses and shares structural homology with the related Severe acute respiratory syndrome coronavirus-1 (SARS-CoV--1). One of the mechanisms for SARS-Cov-1 and-2 infection is mediated by the angiotensin-con-verting enzyme-2 (ACE2) cell receptor, enabling the virus to enter the host cells. ACE2 is an iso-form of the angiotensin-converting enzyme 1 (ACE). The actions of ACE2 counterbalance the clas-sic renin-angiotensin system (RAS) axis through the production of Ang 1-7, which promotes car-diovascular, renal, and lung-protective effects. The ACE2 is not the only route for SARS-CoV-2 to enter the host cells. However, due to its roles in the RAS and its participation in the SARS-CoV-2 virulence, ACE2 has gained attention regarding viral mechanisms of pathogenesis, effects of drugs that interfere with the RAS, and as a potential target for therapeutic strategies for the damages caused by SARS-CoV-2 infection. Among other tissues, ACE2 gene expression seems to be in-creased in the lungs upon SARS-CoV-2 infection;however, amid other variables, expression and/or activity of ACE2 is shown as a disease, sex, and age-dependent. The present review covers critical aspects for a comprehensive understanding of ACE2 and its current involvement in SARS-CoV-2 infection and the development of COVID-19.Copyright © 2021 Bentham Science Publishers.

ACE2 receptor Polymorphism and its correlation with anti-SARS-CoV-2 IgM Antibodies - a case-control study.

BACKGROUND: It has been reported that the SARS-CoV-2 pandemic originated in Wuhan, China in December 2019 and spread rapidly worldwide. The virus gets entry into target cells via angiotensin-converting enzyme 2 (ACE2) receptors and its gene is highly polymorphic. INTRODUCTION: the variations in SARS-CoV-2 susceptibility and severity can be explained on a genetic level by studying the polymorphism in ACE2 receptor polymorphism. OBJECTIVE: A prospective case-control study was designed to compare the ACE2 levels in SARS-CoV-2 patients with the healthy controls in the local population, for which a total of 100 EDTA-containing blood samples were included (50 SARS-CoV-2 IgM positive case and 50 healthy controls). METHODS: PCR-RFLP was performed to investigate the polymorphism of ACE2 in genomic DNA and the ACE2 plasma levels were determined through ELISA. RESULTS: No significant difference in allelic and genotype frequencies (GG, GA, AA) were observed while the ACE2 plasma levels were found to be decreased in positive samples. CONCLUSION: No significant association of the ACE2 gene polymorphism (G8790A) was found with the SARS-CoV-2 susceptibility in the Pakistani population which intimates the search for other genetic factors within the local population.

Mechanisms of Cardiovascular System Injury Induced by COVID-19 in Elderly Patients With Cardiovascular History.

The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), represents a great threat to healthcare and socioeconomics worldwide. In addition to respiratory manifestations, COVID-19 promotes cardiac injuries, particularly in elderly patients with cardiovascular history, leading to a higher risk of progression to critical conditions. The SARS-CoV-2 infection is initiated as virus binding to angiotensin-converting enzyme 2 (ACE2), which is highly expressed in the heart, resulting in direct infection and dysregulation of the renin-angiotensin system (RAS). Meanwhile, immune response and hyper-inflammation, as well as endothelial dysfunction and thrombosis implicate in COVID-19 infection. Herein, we provide an overview of the proposed mechanisms of cardiovascular injuries in COVID-19, particularly in elderly patients with pre-existing cardiovascular diseases, aiming to set appropriate management and improve their clinical outcomes.

Angiotensin-Converting Enzyme 2 (ACE2) in the Context of Respiratory Diseases and Its Importance in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

Angiotensin-Converting Enzyme 2 (ACE2) is an 805 amino acid protein encoded by the ACE2 gene expressed in various human cells, especially in those located in the epithelia. The primary function of ACE2 is to produce angiotensin (1-7) from angiotensin II (Ang II). The current research has described the importance of ACE2 and Ang (1-7) in alternative routes of the renin-angiotensin system (RAS) that promote the downregulation of fibrosis, inflammation, and oxidative stress processes in a great variety of diseases, such as hypertension, acute lung injury, liver cirrhosis, and kidney abnormalities. Investigations into the recent outbreak of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have revealed the importance of ACE2 during infection and its role in recognizing viral binding proteins through interactions with specific amino acids of this enzyme. Additionally, the ACE2 expression in several organs has allowed us to understand the clinical picture related to the infection caused by SARS-CoV-2. This review aims to provide context for the functions and importance of ACE2 with regards to SARS-CoV-2 in the general clinical aspect and its impact on other diseases, especially respiratory diseases.

Effects of Statins on Renin-Angiotensin System.

Statins, a class of drugs for lowering serum LDL-cholesterol, have attracted attention because of their wide range of pleiotropic effects. An important but often neglected effect of statins is their role in the renin-angiotensin system (RAS) pathway. This pathway plays an integral role in the progression of several diseases including hypertension, heart failure, and renal disease. In this paper, the role of statins in the blockade of different components of this pathway and the underlying mechanisms are reviewed and new therapeutic possibilities of statins are suggested.

COVID-19: Zinc and Angiotensin-Converting Enzyme 2 (ACE2) Deficiencies as Determinants of Risk and Severity of Disease: A Narrative Review.

A growing body of evidence supports the premise that deficiencies of zinc and angiotensin-converting enzyme 2 (ACE2, a zinc enzyme) determine severity of coronavirus disease 2019 (COVID-19). ACE2 is part of the renin-angiotensin system (RAS) and acts as a feedback control system moderating blood pressure, keeping blood pressure within normal limits. For a virus to infect a person, the virus has to get inside the person's cells. The virus that causes COVID-19 uses ACE2 to get into the cell. Think of this like an invader from outer space attacking your car by getting in through your cruise control; the RAS is like the cruise control of your car. What happens next depends on how robust your cruise control is. If your cruise control is young and healthy perhaps very little happens; your car may slow down or speed up a bit. But if your cruise control is in poor condition the attack might disrupt the entire speed control system; your car may brake suddenly or speed out of control and crash. Feedback control systems (natural or man-made) are designed to keep dynamic systems in control, but under certain situations can drive the system completely out of control. The RAS is composed of two feedback loops: the ACE loop provides amplification, increasing pro-inflammatory cytokines and blood pressure; the ACE2 loop provides fine control and mitigates the vasoconstrictive, pro-inflammatory, and thrombotic actions of the ACE loop. Usually, there is balance, but in the setting of COVID-19, underlying deficiencies of zinc and ACE2 can lead to an imbalance. Exacerbated by the severe downregulation of ACE2 seen with viral entry, a "tipping point" is reached with loss of control of the RAS system resulting in increased angiotensin II (Ang II) causing downstream vasoconstriction, inflammation, and thromboses. These, in turn, lead to complications often seen in "severe COVID-19" such as acute respiratory distress syndrome (ARDS) or cytokine storm, often seen in high-risk patients in the second week of illness. This model suggests that supplemental zinc could replenish zinc in ACE2, stabilize the ACE2 axis, and prevent disruption of the RAS. This would prevent the vasoconstrictive, inflammatory, and thrombotic actions of Ang II, thus preventing the severe COVID-19 complications which cause the high morbidity and mortality seen in high-risk patients with underlying zinc deficiency. Zinc supplements are available, easy to use, and relatively safe. Randomized clinical trials are needed to confirm safety and efficacy of zinc supplementation to decrease severity of and morality from COVID-19 in high-risk patients. Since replenishment of zinc and active ACE2 in patients in whom these are deficient may take weeks, supplementation in high-risk populations prior to COVID infection may be required. Such supplementation should not replace vaccination but may be useful in populations for whom vaccination is not available or for populations exposed to viral variants to which available vaccines have insufficient coverage.

The fight against COVID-19: Striking a balance in the renin-angiotensin system.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells by interacting with membrane-bound angiotensin-converting enzyme 2 (ACE2), a vital element in the renin-angiotensin system (RAS), which regulates blood pressure, fluid balance, and cardiovascular functions. We herein evaluate existing evidence for the molecular alterations within the RAS pathway (e.g., ACE2 and angiotensin II) during SARS-CoV-2 infection and subsequent Coronavirus Disease 2019 (COVID-19). This includes reports regarding potential effect of RAS blockade (e.g., ACE inhibitors and angiotensin II receptor blockers) on ACE2 expression and clinical outcomes in patients with co-morbidities commonly treated with these agents. The collective evidence suggests a dual role for ACE2 in COVID-19, depending on the stage of infection and the coexisting diseases in individual patients. This information is further discussed with respect to potential therapeutic strategies targeting RAS for COVID-19 treatment.

Effects of angiotensin II receptor blocker usage on viral load, antibody dynamics, and transcriptional characteristics among COVID-19 patients with hypertension.

Epidemiological evidence suggests that patients with hypertension infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at increased risk of acute lung injury. However, it is still not clear whether this increased risk is related to the usage of renin-angiotensin system (RAS) blockers. We collected medical records of coronavirus disease 2019 (COVID-19) patients from the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China), and evaluated the potential impact of an angiotensin II receptor blocker (ARB) on the clinical outcomes of COVID-19 patients with hypertension. A total of 30 hypertensive COVID-19 patients were enrolled, of which 17 were classified as non-ARB group and the remaining 13 as ARB group based on the antihypertensive therapies they received. Compared with the non-ARB group, patients in the ARB group had a lower proportion of severe cases and intensive care unit (ICU) admission as well as shortened length of hospital stay, and manifested favorable results in most of the laboratory testing. Viral loads in the ARB group were lower than those in the non-ARB group throughout the disease course. No significant difference in the time of seroconversion or antibody levels was observed between the two groups. The median levels of soluble angiotensin-converting enzyme 2 (sACE2) in serum and urine samples were similar in both groups, and there were no significant correlations between serum sACE2 and biomarkers of disease severity. Transcriptional analysis showed 125 differentially expressed genes which mainly were enriched in oxygen transport, bicarbonate transport, and blood coagulation. Our results suggest that ARB usage is not associated with aggravation of COVID-19. These findings support the maintenance of ARB treatment in hypertensive patients diagnosed with COVID-19.

Emerging importance of ACE2 in external stratified epithelial tissues.

Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system (RAS), has been identified as the receptor for the SARS-CoV-2. Several RAS components including ACE2 and its substrate Ang II are present in both eye and skin, two stratified squamous epithelial tissues that isolate organisms from external environment. Our recent findings in cornea and others in both skin and eye suggest contribution of this system, and specifically of ACE2 in variety of physiological and pathological responses of these organ systems. This review will focus on the role RAS system plays in both skin and cornea, and will specifically discuss our recent findings on ACE2 in corneal epithelial inflammation, as well as potential implications of ACE2 in patients with COVID-19.

Targeting RAGE to prevent SARS-CoV-2-mediated multiple organ failure: Hypotheses and perspectives.

A novel infectious disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in December 2019 and declared as a global pandemic by the World Health. Approximately 15% of patients with COVID-19 progress to severe pneumonia and eventually develop acute respiratory distress syndrome (ARDS), septic shock and/or multiple organ failure with high morbidity and mortality. Evidence points towards a determinant pathogenic role of members of the renin-angiotensin system (RAS) in mediating the susceptibility, infection, inflammatory response and parenchymal injury in lungs and other organs of COVID-19 patients. The receptor for advanced glycation end-products (RAGE), a member of the immunoglobulin superfamily, has important roles in pulmonary pathological states, including fibrosis, pneumonia and ARDS. RAGE overexpression/hyperactivation is essential to the deleterious effects of RAS in several pathological processes, including hypertension, chronic kidney and cardiovascular diseases, and diabetes, all of which are major comorbidities of SARS-CoV-2 infection. We propose RAGE as an additional molecular target in COVID-19 patients for ameliorating the multi-organ pathology induced by the virus and improving survival, also in the perspective of future infections by other coronaviruses.

The Balance between Two Branches of RAS Can Protect from Severe COVID-19 Course.

The COVID-19 pandemic has swept the world and required the mobilization of scientists and clinicians around the world to combat this serious disease. Along with SARS-CoV-2 virology research, understanding of the fundamental physiological processes, molecular and cellular mechanisms and intracellular signaling pathways underlying the clinical manifestations of COVID-19 is important for effective therapy of this disease. The review describes in detail the interaction of the components of the renin-angiotensin system (RAS) and receptors of end-glycosylated products (RAGE), which plays a special role in normal lung physiology and in pathological conditions in COVID-19, including the development of acute respiratory distress syndrome and "cytokine storm". A separate section is devoted to the latest developments aimed at correcting the dysfunction of the RAS caused by the binding of the virus to angiotensin converting enzyme 2 (ACE2)- the central element of this system. Analysis of published theoretical, clinical, and experimental data indicates the need for a complex treatment to prevent a severe course of COVID-19 using MasR agonists, blockers of the AT1R and NF-κB signaling pathway, as well as compounds with neuroprotective and neuroregenerative effects.

The Two-Way Switch Role of ACE2 in the Treatment of Novel Coronavirus Pneumonia and Underlying Comorbidities.

December 2019 saw the emergence of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which has spread across the globe. The high infectivity and ongoing mortality of SARS-CoV-2 emphasize the demand of drug discovery. Angiotensin-converting enzyme II (ACE2) is the functional receptor for SARS-CoV-2 entry into host cells. ACE2 exists as a membrane-bound protein on major viral target pulmonary epithelial cells, and its peptidase domain (PD) interacts SARS-CoV-2 spike protein with higher affinity. Therefore, targeting ACE2 is an important pharmacological intervention for a SARS-CoV-2 infection. In this review, we described the two-way switch role of ACE2 in the treatment of novel coronavirus pneumonia and underlying comorbidities, and discussed the potential effect of the ACE inhibitor and angiotensin receptor blocker on a hypertension patient with the SARS-CoV-2 infection. In addition, we analyzed the S-protein-binding site on ACE2 and suggested that blocking hot spot-31 and hot spot-353 on ACE2 could be a therapeutic strategy for preventing the spread of SARS-CoV-2. Besides, the recombinant ACE2 protein could be another potential treatment option for SARS-CoV-2 induced acute severe lung failure. This review could provide beneficial information for the development of anti-SARS-CoV-2 agents via targeting ACE2 and the clinical usage of renin-angiotensin system (RAS) drugs for novel coronavirus pneumonia treatment.

Overview of COVID-19 inflammatory pathogenesis from the therapeutic perspective.

The novel beta coronavirus (SARS-CoV-2, designated as COVID-19) that is responsible for severe acute respiratory syndrome has devastated the global economy and health care system. Since COVID-19 changed the definition of "normal" in ordinary life around the world, the development of effective therapeutics and preventive measures is desperately needed to fight SARS-CoV-2 infection and restore normalcy. A clear understanding of COVID-19 pathogenesis is crucial in providing the scientific rationale necessary to develop anti-COVID19 drugs and vaccines. According to the most recently published literature, COVID-19 pathogenesis was postulated to occur in three sequential phases: pulmonary, proinflammatory, and prothrombic. Herein, virus-host interactions, potential pathogenic mechanisms, and clinical manifestations are described for each phase. Additionally, based on this pathogenesis model, various therapeutic strategies involving current clinical trials are presented with an explanation of their modes of action and example drugs. This review is a thorough, updated summary of COVID-19 pathogenesis and the therapeutic options available for this disease.

Renin-angiotensin system inhibitors and mortality in patients with COVID-19.

Association of renin-angiotensin system inhibitors with risk of death in patients with hypertension (HTN) and coronavirus disease 2019 (COVID-19) is not well characterized. The aim of this study was to evaluate the outcomes of patients with HTN and COVID-19 with respect to different chronic antihypertensive drug intake. We performed a retrospective, observational study from a large cohort of patients with HTN and with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection admitted to the Emergency Rooms (ER) of the Piacenza Hospital network from February 21, 2020 to March 20, 2020. There were 1050 patients admitted to the ERs of the Piacenza Hospital network with COVID-19. HTN was present in 590 patients [median age, 76.2 years (IQR 68.2-82.6)]; 399 (66.1%) patients were male. Of them, 248 patients were chronically treated with ACEi, 181 with ARBs, and 161 with other drugs (O-drugs) including beta blockers, diuretics and calcium-channel inhibitors. With respect to the antihypertensive use, there was no difference between comorbid conditions. During a follow-up of 38 days (IQR 7.0-46.0), 256 patients (43.4%) died, without any difference stratifying for antihypertensive drugs. Of them, 107 (43.1%) were in ACEi group vs 67 (37%) in ARBs group vs 82 (50.7%) in O-drugs group, (log-rank test: p = 0.066). In patients with HTN and COVID-19, neither ACEi nor ARBs were independently associated with mortality. After adjusting for potential confounders in risk prediction, the rate of death was similar. Our data confirm Specialty Societal recommendations, suggesting that treatment with ACEIs or ARBs should not be discontinued because of COVID-19.

Impact of Treatment with Renin-Angiotensin System Inhibitors on Clinical Outcomes in Hypertensive Patients Hospitalized with COVID-19.

INTRODUCTION: Concerns have been raised about the possible harmfulness of angiotensin-converter enzyme inhibitors (ACEi) and aldosterone receptor blockers (ARB) in patients with COVID-19. However, few data from a European population have been published, especially from hypertensive patients. AIM: To study the association between ACEi or ARB treatments and major adverse outcomes during hospitalisation in COVID-19 patients. METHODS: We studied 545 consecutive hypertensive patients admitted to our institution due to COVID-19 with respiratory involvement. We analysed the incidence of combined event (death or mechanical ventilatory support) during hospitalisation, as well as the time to independent events. RESULTS: 188 (34.5%) patients presented the combined endpoint. 182 (33.4%) patients died, and 21 (3.9%) needed mechanical ventilatory support. Patients with previous treatment with ACEi or ARB presented similar incidence of the combined endpoint during hospitalisation (31.6% vs. 41.8%; p = 0.08), with a lower all-cause mortality rate (30.4% vs. 41.2%; p = 0.03) compared with those without prior treatment. Use of ACEi or ARB was not independently associated with lower incidence of the combined endpoint [Adjusted OR 0.675 (95% CI 0.298-1.528; p = 0.146)], but it was associated with lower mortality [Adjusted OR 0.550 (95% CI 0.304-0.930; p = 0.047)]. CONCLUSIONS: The use of ACEi or ARB was associated with less incidence of all-cause death during hospitalisation among hypertensive patients admitted with COVID-19 respiratory infection.

Delineating clinical characteristics and comorbidities among 206 COVID-19 deceased patients in India: Emerging significance of renin angiotensin system derangement.

AIM: While there are rampant deaths reported worldwide due to novel corona virus (COVID-19) on one side, hypertension, diabetes and renal failure are emerging comorbidities with mortality risk due to respiratory failure on the other side. The link of these morbidities with renin angiotensin system (RAS) and angiotensin converting enzyme-2 (ACE2) as the site of the multiplication of COVID-19 has widely been accepted. The objective of this research report was to delineate the clinical characteristics with COVID-19 infection with RAS and to consider its significance not just for the search of novel antiviral drugs, but for the management and prevention of death of patients with COVID-19. METHODS: It was a retrospective case series analysis of demographic and clinical data with associated comorbidities of 206 deaths reported in India up to 10th April 2020. The data were available from the official release from Ministry of Health and Family welfare, Government of India. This was followed by a literature search to correlate the available evidence for their possible relationship with RAS. RESULTS: The demographic data were consistent with those reported from other countries. The death (53.4%) was more common in patients with age above 60 years and men (69.3%) were more susceptible as compared to women (30.68%).We found that 50.5% of the deceased patients had pre-existing comorbidities. Diabetes and hypertension were the major comorbidities in 27.8% and 22.1% of the deceased cases respectively. Although respiratory and cardiac problems were prevalent at the time of death, the pre-existing pulmonary disease was comparatively less prevalent. Only 13.6% of the deceased were having pre-existing respiratory problems and 6.2% had cardiac ailments. We could correlate the reports that RAS plays a significant role in the prognosis of the disease. CONCLUSIONS: Patients with cardiovascular diseases, diabetes mellitus and hypertension are at greater risk for developing COVID-19 infection. There may be massive derangement of the entire RAS after the attack of COVID-19 and hence, patients with these pre-existing comorbidities and on ACE inhibitors or angiotensin receptor blockers should be monitored carefully considering the role of RAS in the prognosis of COVID-19 infections.

COVID-19 and Obesity: Dangerous Liaisons.

Besides advanced age and the presence of multiple comorbidities as major contributors to increased risk of severe disease and fatal outcome from Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19), there is now emerging evidence that overweight and obesity predispose to severe symptoms and negative prognosis. Remarkably, the severity of COVID-19 appears to rise with increasing body mass index (BMI). The association between COVID-19 outcomes and overweight/obesity has biological and physiological plausibility. Potential pathophysiological mechanisms that may explain this strong association include the chronic pro-inflammatory state, the excessive oxidative stress response, and the impaired immunity that is commonly reported in these individuals. The role of cytokines, mammalian target of rapamycin (mTOR), and altered natural killer cell polarization in the dangerous liaison between COVID-19 and obesity are discussed here. These pathways can favor and accelerate the deleterious downstream cellular effects of SARS-CoV-2. Moreover, obesity is well known to be associated with reduced lung function and poor response to mechanical ventilation, thus placing these individuals at high risk of severe illness and mortality from COVID-19. Furthermore, obesity may lead to other complications, such as renal failure, cardiovascular dysfunction, hypertension, and vascular damage, which in turn can further accelerate negative clinical outcomes from COVID-19. Obese individuals should be shielded against any potential viral exposure to SARS-CoV-2 with consequential considerations for compulsory protection devices and social distancing. Health care providers should be aware that obesity predisposes to severe symptoms and negative prognosis in COVID-19 patients.

The Lung, the Heart, the Novel Coronavirus, and the Renin-Angiotensin System; The Need for Clinical Trials.

Angiotensin-converting enzyme 2 (ACE2) is the receptor for COVID-19 (SARs-CoV-2). ACE2 protects the lung and heart from acute respiratory distress syndrome (ARDS) and acute myocarditis and arrhythmias, because it breaks down Angiotensin II, which has inflammatory effects in the lung and heart as well as in the kidney. When SARS-CoV-2 binds to ACE2, it suppresses it, so this protective action of ACE2 is lost. Death from COVID-19 is due to ARDS and also heart failure and acute cardiac injury. Drugs that prevent the inflammatory actions of Angiotensin II (i.e., Angiotensin receptor blockers, ARBs) prevent acute lung injury caused by SARS-CoV. Clinical trials are underway to test the risks and benefits of ARBs and angiotensin-converting enzyme inhibitors (ACEIs) in COVID-19 patients requiring hospitalization. Other potential treatments are also discussed.