scholarly journals Asthma and COVID-19: who wins the contested territory of the lower airways?

2021 ◽  
Vol 10 (12) ◽  
pp. e17101220110
Author(s):  
Taís de Lima e Fraga ◽  
Waldemar de Paula Junior ◽  
Marileia Chaves Andrade
Keyword(s):  
Target Cells ◽  
Chronic Asthma ◽  
Th2 Response ◽  
Angiotensin Converting Enzyme 2 ◽  
Asthmatic Patients ◽  
Coronavirus Infection ◽  
Inflammatory Profile ◽  
Limited Possibility ◽  
Pro Inflammatory Cytokines

Among the numerous published studies on COVID-19 in a pandemic year, few listed asthma as a comorbidity, making it therefore difficult to draw any solid conclusions. The respiratory allergy and controlled exposures to allergens are associated with significant reductions in the expression of angiotensin-converting enzyme 2 (ACE2), receptor for SARS-CoV-2 entry into human cells. There is a hypothesis that patients with chronic asthma, due to the type 2 inflammatory profile, may be potentially resistant to developing a severe clinical course of COVID-19. The low IFN-g-mediated response in the respiratory tract of asthmatic patients could limit ACE2 expression in the target cells of SARS-CoV-2 infection. The inflammatory profile of the airways in patients with chronic asthma is mainly related to a Th2 response in type-2 asthma, with production of IL-4, IL-13 and IL-5, presenting antagonistic relationship with pro-inflammatory cytokines such as IFN-g, produced at high levels in severe COVID-19. Published studies, for the most part, are retrospective and may have loss of information or present material with limited possibility for more robust and conclusive analysis. It is important to discuss how patients with atopic or nonatopic asthma seem to protect themselves from new coronavirus infection and how asthma affects COVID-19 and the course of the disease, since there is no increased mortality in asthmatic patients with COVID-19 compared to non-asthmatic patients.

scholarly journals Comparison of the COVID-2019 (SARS-CoV-2) pathogenesis with SARS-CoV and MERS-CoV infections

2020 ◽  
Vol 15 (5) ◽  
pp. 317-323 ◽  
Author(s):  
Mona Fani ◽  
Ali Teimoori ◽  
Shokouh Ghafari
Keyword(s):  
Small Intestine ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Target Cells ◽  
Specific Drug ◽  
Converting Enzyme ◽  
Wholesale Market ◽  
Angiotensin Converting Enzyme 2 ◽  
Therapy Options ◽  
Coronavirus Infection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in several patients who traveled to Wuhan or went to a seafood wholesale market in Wuhan. The phylogenetic tree showed that SARS-CoV-2 was 96.2% identical to bat β-coronaviruses from lineage B. Also, several studies reported that SARS-CoV-2 uses the SARS-CoV receptor, angiotensin-converting enzyme 2, for entry to target cells. Lung alveolar and small intestine are potential targets for SARS-CoV-2 due to the high expression of the angiotensin-converting enzyme 2 receptor. In this review, we focused on the zoonotic β-coronaviruses and given there is no specific drug or vaccine for coronavirus disease 2019, we reviewed the literature on the therapy options for SARS and Middle East respiratory syndrome coronavirus infection, in order to discover their possible use in the treatment of SARS-CoV-2 infections.

scholarly journals Coronavirus Infections and Type 2 Diabetes—Shared Pathways with Therapeutic Implications

2020 ◽  
Vol 41 (3) ◽  
pp. 457-470 ◽  
Author(s):  
Daniel J Drucker
Keyword(s):  
Type 2 Diabetes ◽  
Viral Infections ◽  
Biological Activities ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
Therapeutic Implications ◽  
Increased Risk ◽  
Coronavirus Infection ◽  
Coronavirus Infections

Abstract Abstract Individuals with diabetes are at increased risk for bacterial, mycotic, parasitic, and viral infections. The severe acute respiratory syndrome (SARS)-CoV-2 (also referred to as COVID-19) coronavirus pandemic highlights the importance of understanding shared disease pathophysiology potentially informing therapeutic choices in individuals with type 2 diabetes (T2D). Two coronavirus receptor proteins, angiotensin-converting enzyme 2 (ACE2) and dipeptidyl peptidase-4 (DPP4) are also established transducers of metabolic signals and pathways regulating inflammation, renal and cardiovascular physiology, and glucose homeostasis. Moreover, glucose-lowering agents such as the DPP4 inhibitors, widely used in subjects with T2D, are known to modify the biological activities of multiple immunomodulatory substrates. Here, we review the basic and clinical science spanning the intersections of diabetes, coronavirus infections, ACE2, and DPP4 biology, highlighting clinical relevance and evolving areas of uncertainty underlying the pathophysiology and treatment of T2D in the context of coronavirus infection.

scholarly journals Russian Medical Society for Arterial Hypertension Expert Consensus: Hypertension and COVID-19

2020 ◽  
Vol 17 (3) ◽  
pp. 35-41
Author(s):  
Irina E. Chazova ◽  
Natalia V. Blinova ◽  
Vera A. Nevzorova ◽  
Juliya V. Zhernakova ◽  
Mikhail P. Savenkov ◽  
...  
Keyword(s):  
Arterial Hypertension ◽  
Medical Society ◽  
Target Cells ◽  
The Novel ◽  
Angiotensin Converting Enzyme 2 ◽  
High Prevalence ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
The Relationship ◽  
Russian Medical

The novel coronavirus infection (COVID-19) caused by the b-coronavirus SARS-CoV-2, and leads to acute respiratory distress-syndrome, has affected more than nineteen million people worldwide, resulting in 0.7 million deaths as of August 2020. The fact that the virus uses angiotensin-converting enzyme 2 as a receptor for entering the target cell, and the high prevalence of hypertension and other cardiovascular diseases among patients with COVID-19, have caused serious discussions on the management of such patients. This consensus of experts from the Russian Medical Society for Arterial Hypertension analyzed the existing data on the relationship between COVID-19 and hypertension, the pathophysiological aspects of the penetration of the virus into target cells and the use of renin-angiotensin-aldosterone system inhibitors in patients with hypertension and COVID-19.

scholarly journals ACE2 Is an Adjacent Element of Atherosclerosis and COVID-19 Pathogenesis

2021 ◽  
Vol 22 (9) ◽  
pp. 4691
Author(s):  
Anastasia V. Poznyak ◽  
Evgeny E. Bezsonov ◽  
Ali H. Eid ◽  
Tatyana V. Popkova ◽  
Ludmila V. Nedosugova ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Renin Angiotensin System ◽  
Myocardial Damage ◽  
Angiotensin Converting Enzyme 2 ◽  
Adjacent Element ◽  
Chinese Province ◽  
Coronavirus Infection ◽  
First Time ◽  
The Relationship ◽  
Interspecies Barrier

COVID-19 is a highly contagious new infection caused by the single-stranded RNA Sars-CoV-2 virus. For the first time, this infection was recorded in December 2019 in the Chinese province of Wuhan. The virus presumably crossed the interspecies barrier and passed to humans from a bat. Initially, the disease was considered exclusively in the context of damage to the respiratory system, but it quickly became clear that the disease also entails serious consequences from various systems, including the cardiovascular system. Among these consequences are myocarditis, myocardial damage, subsequent heart failure, myocardial infarction, and Takotsubo syndrome. On the other hand, clinical data indicate that the presence of chronic diseases in a patient aggravates the course and outcome of coronavirus infection. In this context, the relationship between COVID-19 and atherosclerosis, a condition preceding cardiovascular disease and other disorders of the heart and blood vessels, is particularly interesting. The renin-angiotensin system is essential for the pathogenesis of both coronavirus disease and atherosclerosis. In particular, it has been shown that ACE2, an angiotensin-converting enzyme 2, plays a key role in Sars-CoV-2 infection due to its receptor activity. It is noteworthy that this enzyme is important for the normal functioning of the cardiovascular system. Disruptions in its production and functioning can lead to various disorders, including atherosclerosis.

scholarly journals Type-2 Diabetes as a Risk Factor for Severe COVID-19 Infection

2021 ◽  
Vol 9 (6) ◽  
pp. 1211
Author(s):  
Mahnaz Norouzi ◽  
Shaghayegh Norouzi ◽  
Alistaire Ruggiero ◽  
Mohammad S. Khan ◽  
Stephen Myers ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Factor ◽  
Inflammatory Responses ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Diabetic Patients ◽  
Angiotensin Converting Enzyme 2 ◽  
Immune System Dysfunction ◽  
Current Outbreak

The current outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19), has generated a notable challenge for diabetic patients. Overall, people with diabetes have a higher risk of developing different infectious diseases and demonstrate increased mortality. Type 2 diabetes mellitus (T2DM) is a significant risk factor for COVID-19 progression and its severity, poor prognosis, and increased mortality. How diabetes contributes to COVID-19 severity is unclear; however, it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Using the envelope spike glycoprotein SARS-CoV-2, COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) receptors, a key protein expressed in metabolic organs and tissues such as pancreatic islets. Therefore, it has been suggested that diabetic patients are more susceptible to severe SARS-CoV-2 infections, as glucose metabolism impairments complicate the pathophysiology of COVID-19 disease in these patients. In this review, we provide insight into the COVID-19 disease complications relevant to diabetes and try to focus on the present data and growing concepts surrounding SARS-CoV-2 infections in T2DM patients.

scholarly journals Pathological Role of Angiotensin II in Severe COVID-19

TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e138-e144 ◽  
Author(s):  
Wolfgang Miesbach
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Treatment Options ◽  
Renin Angiotensin System ◽  
Target Cells ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Novel Coronavirus

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.

scholarly journals Regulation of bronchial epithelial barrier integrity by type 2 cytokines and histone deacetylases in asthmatic patients

2017 ◽  
Vol 139 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Paulina Wawrzyniak ◽  
Marcin Wawrzyniak ◽  
Kerstin Wanke ◽  
Milena Sokolowska ◽  
Kreso Bendelja ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Epithelial Barrier ◽  
Bronchial Epithelial ◽  
Barrier Integrity ◽  
Asthmatic Patients ◽  
Type 2 Cytokines

Abstract 657: Increased Urinary Angiotensin Converting Enzyme 2 (ACE2) In Type 2 Diabetic Patients

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Sridevi Gutta ◽  
Nadja Grobe ◽  
Hassan Osman ◽  
Mohammad Saklayen ◽  
Khalid M Elased
Keyword(s):  
Mass Spectrometry ◽  
Medical Center ◽  
Diabetic Patients ◽  
Enzyme Assays ◽  
Renal Tubules ◽  
Type 2 Diabetic Patients ◽  
Major Health ◽  
Angiotensin Converting Enzyme 2 ◽  
Noninvasive Biomarker

Diabetes and its associated chronic kidney disease (CKD) is a major health burden and there is an urgent need for new sensitive biomarkers to detect and monitor the progression of CKD. Albuminuria is still the gold standard for the evaluation of kidney function. However, its sensitivity and reliability have recently been questioned. ACE2 is highly expressed in renal tubules and has been shown to be shed in the urine of diabetic patients with CKD. The aim of the study was to investigate whether urinary ACE2 is increased in diabetic patients with CKD before the onset of microalbuminuria. Participants were recruited from Dayton VA Medical Center (Dayton, OH, USA). Baseline urinary albumin creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were determined three months before initiation of the study in non-diabetic patients (UACR <30 mg/g, eGFR=97.40±16 ml/min/1.73 m 2 ), and in diabetic patients with normoalbuminuria (UACR <30 mg/g, eGFR=83.08±17 ml/min/1.73 m 2 ), microalbuminuria (UACR = 30-300 mg/g, eGFR=47.13±23 ml/min/1.73 m 2 ), and macroalbuminuria (UACR >300 mg/g, eGFR=39.68±20 ml/min/1.73 m 2 ). Using fluorogenic and mass spectrometry-based enzyme assays, we measured urinary and plasma ACE2 activity in patients. Urinary ACE2 activity was significantly increased in diabetic patients with normoalbuminuria (0.58±0.2 nmol/hr/mg creatinine), microalbuminuria (1.19 ±0.5 nmol/hr/mg creatinine), and macroalbuminuria (2.265±0.4 nmol/hr/mg creatinine) compared with non-diabetic controls (0.06 ± 0.02 nmols/hr/mg creatinine) (p<0.0001). These results were confirmed by detecting the ACE2 product Ang-(1-7) ( m/z 899) in incubations of urine samples with the natural substrate Ang II ( m/z 1046) using mass spectrometry-based enzyme assays. In addition, urinary ACE2 expression was significantly increased in diabetic patients as determined by western blot analysis (p<0.05). Plasma ACE2 activity was not detectable in control and diabetic patients. In conclusion, urinary ACE2 is increased in diabetic patients with CKD which suggests that urinary ACE2 could be used as an early, noninvasive biomarker for diabetic nephropathy before the onset of microalbuminuria.

scholarly journals December 2021 Pulmonary Case of the Month: Interstitial Lung Disease with Red Knuckles

2021 ◽  
Vol 23 (6) ◽  
pp. 151-154
Author(s):  
Richard Robbins ◽  
◽  
Stephen Klotz
Keyword(s):  
Interstitial Lung Disease ◽  
Inpatient Care ◽  
Rna Viruses ◽  
Specific Binding ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
A Cell ◽  
Coronavirus Infection

No abstract available. Article truncated after 150 words. We thought a follow-up to our original brief review of COVID-19 in February, 2020 might be useful. As we write this in early December 2021, we again caution that this area is rapidly changing and what is true today will likely be outdated tomorrow. We again borrowed heavily from the Centers for Disease Control (CDC) CDC website and the NIH website which have extensive discussions over numerous pages covering COVID-19. Our hope is to condense those recommendations. We do not discuss inpatient care in any detail. COVID-19 Variants The initial steps of coronavirus infection involve the specific binding of the coronavirus spike (S) protein to the cellular entry receptors which are normally on a cell. These include human aminopeptidase N (APN; HCoV-229E), angiotensin-converting enzyme 2 (ACE2; HCoV-NL63, SARS-CoV and SARS-CoV-2) and dipeptidyl peptidase 4 (DPP4; MERS-CoV). All viruses, but especially simple single-stranded RNA viruses like COVID-19, constantly change through mutation …

scholarly journals METFORMIN USE IN DIABETES PRIOR TO HOSPITALIZATION: EFFECTS ON MORTALITY IN COVID-19

2020 ◽  
Vol 26 (10) ◽  
pp. 1166-1172
Author(s):  
Jinghong Li ◽  
Qi Wei ◽  
Willis X. Li ◽  
Karen C. McCowen ◽  
Wei Xiong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Clinical Data ◽  
Laboratory Data ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

Objective: Although type 2 diabetes mellitus (T2DM) has been reported as a risk factor for coronavirus disease 2019 (COVID-19), the effect of pharmacologic agents used to treat T2DM, such as metformin, on COVID-19 outcomes remains unclear. Metformin increases the expression of angiotensin converting enzyme 2, a known receptor for severe acute respiratory syndrome coronavirus 2. Data from people with T2DM hospitalized for COVID-19 were used to test the hypothesis that metformin use is associated with improved survival in this population. Methods: Retrospective analyses were performed on de-identified clinical data from a major hospital in Wuhan, China, that included patients with T2DM hospitalized for COVID-19 during the recent epidemic. One hundred and thirty-one patients diagnosed with COVID-19 and T2DM were used in this study. The primary outcome was mortality. Demographic, clinical characteristics, laboratory data, diabetes medications, and respiratory therapy data were also included in the analysis. Results: Of these 131 patients, 37 used metformin with or without other antidiabetes medications. Among the 37 metformin-taking patients, 35 (94.6%) survived and 2 (5.4%) did not survive. The mortality rates in the metformin-taking group versus the non-metformin group were 5.4% (2/37) versus 22.3% (21/94). Using multivariate analysis, metformin was found to be an independent predictor of survival in this cohort ( P = .02). Conclusion: This study reveals a significant association between metformin use and survival in people with T2DM diagnosed with COVID-19. These clinical data are consistent with potential benefits of the use of metformin for COVID-19 patients with T2DM. Abbreviations: ACE2 = angiotensin-converting enzyme 2; AMPK = AMP-activated protein kinase; BMI = body mass index; COVID-19 = coronavirus disease 2019; SARSCoV-2 = severe acute respiratory syndrome coronavirus 2; T2DM = type 2 diabetes mellitus

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