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Article ; Online: Obesity Is a Risk Factor for Severe COVID-19 Infection: Multiple Potential Mechanisms.

Sattar, Naveed / McInnes, Iain B / McMurray, John J V

2020 Volume 142, Issue 1, Page(s) 4–6

MeSH term(s)	Betacoronavirus/isolation & purification ; Body Mass Index ; COVID-19 ; Cardiovascular Diseases/complications ; Cardiovascular Diseases/pathology ; Coronavirus Infections/etiology ; Coronavirus Infections/pathology ; Coronavirus Infections/virology ; Forced Expiratory Volume ; Humans ; Lung/physiology ; Obesity/complications ; Obesity/pathology ; Pandemics ; Pneumonia, Viral/etiology ; Pneumonia, Viral/pathology ; Pneumonia, Viral/virology ; Risk Factors ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-04-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.120.047659
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Article: Obesity Is a Risk Factor for Severe COVID-19 Infection: Multiple Potential Mechanisms

Sattar, Naveed / McInnes, Iain B / McMurray, John J V

Circulation

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #108945
Database	COVID19

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Article ; Online: Obesity Is a Risk Factor for Severe COVID-19 Infection ; Multiple Potential Mechanisms

Sattar, Naveed / McInnes, Iain B. / McMurray, John J.V.

Circulation

2020 Volume 142, Issue 1, Page(s) 4–6

Keywords	Physiology (medical) ; Cardiology and Cardiovascular Medicine ; covid19
Language	English
Publisher	Ovid Technologies (Wolters Kluwer Health)
Publishing country	us
Document type	Article ; Online
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/circulationaha.120.047659
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cross-Talk of NADPH Oxidases and Inflammation in Obesity

Morawietz, Henning / Brendel, Heike / Diaba-Nuhoho, Patrick / Catar, Rusan / Perakakis, Nikolaos / Wolfrum, Christian / Bornstein, Stefan R.

Antioxidants. 2023 Aug. 09, v. 12, no. 8

2023

Abstract: Obesity is a major risk factor for cardiovascular and metabolic diseases. Multiple experimental and ... in experimental models and clinical studies of obesity, cardiovascular diseases, COVID-19 infections and potential ... tissues. Increasing evidence supports the idea of an increased risk for severe clinical complications ...

Abstract	Obesity is a major risk factor for cardiovascular and metabolic diseases. Multiple experimental and clinical studies have shown increased oxidative stress and inflammation linked to obesity. NADPH oxidases are major sources of reactive oxygen species in the cardiovascular system and in metabolically active cells and organs. An impaired balance due to the increased formation of reactive oxygen species and a reduced antioxidative capacity contributes to the pathophysiology of cardiovascular and metabolic diseases and is linked to inflammation as a major pathomechanism in cardiometabolic diseases. Non-alcoholic fatty liver disease is particularly characterized by increased oxidative stress and inflammation. In recent years, COVID-19 infections have also increased oxidative stress and inflammation in infected cells and tissues. Increasing evidence supports the idea of an increased risk for severe clinical complications of cardiometabolic diseases after COVID-19. In this review, we discuss the role of oxidative stress and inflammation in experimental models and clinical studies of obesity, cardiovascular diseases, COVID-19 infections and potential therapeutic strategies.
Keywords	COVID-19 infection ; antioxidant activity ; cardiovascular system ; fatty liver ; inflammation ; obesity ; oxidative stress ; oxidoreductases ; pathophysiology ; reactive oxygen species ; risk factors ; therapeutics
Language	English
Dates of publication	2023-0809
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12081589
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Obesity as a Risk Factor for Severe COVID-19 and Complications: A Review.

Demeulemeester, Fien / de Punder, Karin / van Heijningen, Marloes / van Doesburg, Femke

Cells

2021 Volume 10, Issue 4

Abstract: ... in this high-risk group. We propose that multiple features of obesity contribute to the prevalence of severe ... Emerging data suggest that obesity is a major risk factor for the progression of major ... clinical findings on the relationship between obesity and COVID-19 disease severity and then further ...

Abstract	Emerging data suggest that obesity is a major risk factor for the progression of major complications such as acute respiratory distress syndrome (ARDS), cytokine storm and coagulopathy in COVID-19. Understanding the mechanisms underlying the link between obesity and disease severity as a result of SARS-CoV-2 infection is crucial for the development of new therapeutic interventions and preventive measures in this high-risk group. We propose that multiple features of obesity contribute to the prevalence of severe COVID-19 and complications. First, viral entry can be facilitated by the upregulation of viral entry receptors, like angiotensin-converting enzyme 2 (ACE2), among others. Second, obesity-induced chronic inflammation and disruptions of insulin and leptin signaling can result in impaired viral clearance and a disproportionate or hyper-inflammatory response, which together with elevated ferritin levels can be a direct cause for ARDS and cytokine storm. Third, the negative consequences of obesity on blood coagulation can contribute to the progression of thrombus formation and hemorrhage. In this review we first summarize clinical findings on the relationship between obesity and COVID-19 disease severity and then further discuss potential mechanisms that could explain the risk for major complications in patients suffering from obesity.
MeSH term(s)	Animals ; COVID-19/complications ; COVID-19/immunology ; COVID-19/pathology ; Chronic Disease ; Humans ; Immunity ; Inflammation/complications ; Inflammation/immunology ; Inflammation/pathology ; Insulin Resistance ; Obesity/complications ; Obesity/immunology ; Obesity/pathology ; Risk Factors ; SARS-CoV-2/immunology ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/physiology ; Severity of Illness Index ; Unfolded Protein Response ; Virus Internalization
Language	English
Publishing date	2021-04-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10040933
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Obesity as a Risk Factor for Severe COVID-19 and Complications

Fien Demeulemeester / Karin de Punder / Marloes van Heijningen / Femke van Doesburg

Cells, Vol 10, Iss 933, p

A Review

2021 Volume 933

Abstract	Emerging data suggest that obesity is a major risk factor for the progression of major complications such as acute respiratory distress syndrome (ARDS), cytokine storm and coagulopathy in COVID-19. Understanding the mechanisms underlying the link between obesity and disease severity as a result of SARS-CoV-2 infection is crucial for the development of new therapeutic interventions and preventive measures in this high-risk group. We propose that multiple features of obesity contribute to the prevalence of severe COVID-19 and complications. First, viral entry can be facilitated by the upregulation of viral entry receptors, like angiotensin-converting enzyme 2 (ACE2), among others. Second, obesity-induced chronic inflammation and disruptions of insulin and leptin signaling can result in impaired viral clearance and a disproportionate or hyper-inflammatory response, which together with elevated ferritin levels can be a direct cause for ARDS and cytokine storm. Third, the negative consequences of obesity on blood coagulation can contribute to the progression of thrombus formation and hemorrhage. In this review we first summarize clinical findings on the relationship between obesity and COVID-19 disease severity and then further discuss potential mechanisms that could explain the risk for major complications in patients suffering from obesity.
Keywords	coagulopathy ; COVID-19 ; cytokine storm ; inflammation ; leptin ; obesity ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The association between obesity and poor outcome after COVID-19 indicates a potential therapeutic role for montelukast.

Almerie, Muhammad Qutayba / Kerrigan, David Daniel

Medical hypotheses

2020 Volume 143, Page(s) 109883

Abstract: ... striking how dangerous the combination of obesity and COVID-19 is, resulting in a greater risk of ICU ... the heightened cytokine activity seen in obesity, the major risk factor for a poor prognosis in COVID-19 ... storm' is postulated as the mechanism behind the extreme immune response seen in severe COVID-19. It is ...

Abstract	It is widely believed that infection with the SARS-CoV-2 virus triggers a disproportionate immune response which causes a devastating systemic injury, particularly in individuals with obesity, itself a chronic, multi-organ inflammatory disease. Immune cells accumulate in visceral adipose tissue and together with paracrine adipocytes release a wide range of biologically active cytokines (including IL-1β, IL5, IL6 and IL8) that can result in both local, pulmonary and systemic inflammation. A more intense 'cytokine storm' is postulated as the mechanism behind the extreme immune response seen in severe COVID-19. It is striking how dangerous the combination of obesity and COVID-19 is, resulting in a greater risk of ICU admission and a higher mortality. Furthermore, patients from a BAME background appear to have increased mortality after SARS-CoV-2 infection; they also have a higher prevalence of central obesity and its metabolic complications. In the absence of an effective vaccine, the therapeutic potential of immune-modulating drugs is a priority, but the development of new drugs is expensive and time-consuming. A more pragmatic solution would be to seek to repurpose existing drugs, particularly those that might suppress the heightened cytokine activity seen in obesity, the major risk factor for a poor prognosis in COVID-19. Montelukast is a cysteinyl leukotriene receptor antagonist licensed to treat asthma and allergic rhinitis. It has been shown to diminish pulmonary response to antigen, tissue eosinophilia and IL-5 expression in inflammatory cells. It has also been shown to decrease elevated levels of IL-1β and IL8 in humans with viral upper respiratory tract infections compared with placebo-treated patients. In addition, in silico studies have demonstrated a high binding affinity of the montelukast molecule to the terminal site of the virus's main protease enzyme which is needed for virus RNA synthesis and replication. Montelukast, which is cheap, safe and widely available would appear to have the potential to be an ideal candidate drug for clinical trials, particularly in early stage disease before irreparable tissue damage has already occurred. HYPOTHESIS: Through a direct anti-viral effect, or by suppression of heightened cytokine release in response to SARS-CoV-2, montelukast will reduce the severity of immune-mediated multiorgan damage resulting from COVID-19, particularly in patients with central obesity and metabolic syndrome.
MeSH term(s)	Acetates/therapeutic use ; Antiviral Agents/therapeutic use ; Betacoronavirus/drug effects ; Betacoronavirus/enzymology ; COVID-19 ; Coronavirus 3C Proteases ; Coronavirus Infections/complications ; Coronavirus Infections/drug therapy ; Cysteine Endopeptidases ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/etiology ; Drug Repositioning ; Humans ; Immunologic Factors/therapeutic use ; Inflammation/drug therapy ; Inflammation/etiology ; Leukotriene Antagonists/therapeutic use ; Obesity/complications ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/drug therapy ; Quinolines/therapeutic use ; SARS-CoV-2 ; Viral Nonstructural Proteins/antagonists & inhibitors
Chemical Substances	Acetates ; Antiviral Agents ; Immunologic Factors ; Leukotriene Antagonists ; Quinolines ; Viral Nonstructural Proteins ; Cysteine Endopeptidases (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28) ; montelukast (MHM278SD3E)
Keywords	covid19
Language	English
Publishing date	2020-05-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2020.109883
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: L‐arginine as a potential GLP‐1‐mediated immunomodulator of Th17‐related cytokines in people with obesity and asthma

Liao, Shu‐Yi / Linderholm, Angela / Showalter, Megan R. / Chen, Ching‐Hsien / Fiehn, Oliver / Kenyon, Nicholas J.

Obesity science & practice. 2021 June, v. 7, no. 3

2021

Abstract: Obesity is considered as a risk factor for COVID‐19 with insulin resistance and increased ... cytokine levels and improves insulin deficiency or resistance, both are two big risk factors for COVID‐19 ... inhaled nitric oxide are proposed therapeutic approaches to treat COVID‐19 because of their broad anti ...

Abstract	Obesity is considered as a risk factor for COVID‐19 with insulin resistance and increased production of inflammatory cytokines as likely mechanisms. Glucagon‐like peptide‐1 (GLP‐1) agonists and inhaled nitric oxide are proposed therapeutic approaches to treat COVID‐19 because of their broad anti‐inflammatory effects. One approach that might augment GLP‐1 levels would be dietary supplementation with L‐arginine. Beyond cytokines, multiple studies have started to investigate the relationship between new‐onset diabetes and COVID‐19. In a posthoc analysis of a randomized, placebo‐controlled human clinical trial of L‐arginine supplementation in people with asthma and predominantly with obesity, the results showed that 12 weeks of continuous L‐arginine supplementation significantly decreased the level of IL‐21 (p = 0.02) and increased the level of insulin (p = 0.02). A high arginine level and arginine/ADMA ratio were significantly associated with lower CCL‐20 and TNF‐α levels. The study also showed that L‐arginine supplementation reduces cytokine levels and improves insulin deficiency or resistance, both are two big risk factors for COVID‐19 severity and mortality. Given its safety profile and ease of accessibility, L‐arginine is an attractive potential therapeutic option that allows for a cost‐effective way to improve outcomes in patients. An expedition of further investigation or clinical trials to test these hypotheses is needed.
Keywords	COVID-19 infection ; arginine ; asthma ; clinical trials ; cost effectiveness ; diabetes ; dietary supplements ; glucagon-like peptide 1 ; humans ; immunomodulators ; insulin ; insulin resistance ; interleukin-21 ; mortality ; nitric oxide ; obesity ; people ; risk factors ; therapeutics
Language	English
Dates of publication	2021-06
Size	p. 339-345.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2836381-4
ISSN	2055-2238
ISSN	2055-2238
DOI	10.1002/osp4.500
Database	NAL-Catalogue (AGRICOLA)

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Article: The association between obesity and poor outcome after COVID-19 indicates a potential therapeutic role for montelukast

Almerie, Muhammad Qutayba / Kerrigan, David Daniel

Med Hypotheses

Abstract	It is widely believed that infection with the SARS-CoV-2 virus triggers a disproportionate immune response which causes a devastating systemic injury, particularly in individuals with obesity, itself a chronic, multi-organ inflammatory disease. Immune cells accumulate in visceral adipose tissue and together with paracrine adipocytes release a wide range of biologically active cytokines (including IL-1ß, IL5, IL6 and IL8) that can result in both local, pulmonary and systemic inflammation. A more intense 'cytokine storm' is postulated as the mechanism behind the extreme immune response seen in severe COVID-19. It is striking how dangerous the combination of obesity and COVID-19 is, resulting in a greater risk of ICU admission and a higher mortality. Furthermore, patients from a BAME background appear to have increased mortality after SARS-CoV-2 infection; they also have a higher prevalence of central obesity and its metabolic complications. In the absence of an effective vaccine, the therapeutic potential of immune-modulating drugs is a priority, but the development of new drugs is expensive and time-consuming. A more pragmatic solution would be to seek to repurpose existing drugs, particularly those that might suppress the heightened cytokine activity seen in obesity, the major risk factor for a poor prognosis in COVID-19. Montelukast is a cysteinyl leukotriene receptor antagonist licensed to treat asthma and allergic rhinitis. It has been shown to diminish pulmonary response to antigen, tissue eosinophilia and IL-5 expression in inflammatory cells. It has also been shown to decrease elevated levels of IL-1ß and IL8 in humans with viral upper respiratory tract infections compared with placebo-treated patients. In addition, in silico studies have demonstrated a high binding affinity of the montelukast molecule to the terminal site of the virus's main protease enzyme which is needed for virus RNA synthesis and replication. Montelukast, which is cheap, safe and widely available would appear to have the potential to be an ideal candidate drug for clinical trials, particularly in early stage disease before irreparable tissue damage has already occurred. HYPOTHESIS: Through a direct anti-viral effect, or by suppression of heightened cytokine release in response to SARS-CoV-2, montelukast will reduce the severity of immune-mediated multiorgan damage resulting from COVID-19, particularly in patients with central obesity and metabolic syndrome.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #401397
Database	COVID19

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Article ; Online: The association between obesity and poor outcome after COVID-19 indicates a potential therapeutic role for montelukast

Almerie, Muhammad Qutayba / Kerrigan, David Daniel

issn: 03069877

2020

Abstract: ... the combination of obesity and COVID-19 is, resulting in a greater risk of ICU admission and a higher mortality ... the major risk factor for a poor prognosis in COVID-19. Montelukast is a cysteinyl leukotriene receptor ... as the mechanism behind the extreme immune response seen in severe COVID-19. It is striking how dangerous ...

Abstract	From Elsevier via Jisc Publications Router History: accepted 2020-05-25, epub 2020-05-31, issue date 2020-10-31 Article version: VoR Publication status: Published Abstract It is widely believed that infection with the SARS-CoV-2 virus triggers a disproportionate immune response which causes a devastating systemic injury, particularly in individuals with obesity, itself a chronic, multi-organ inflammatory disease. Immune cells accumulate in visceral adipose tissue and together with paracrine adipocytes release a wide range of biologically active cytokines (including IL-1β, IL5, IL6 and IL8) that can result in both local, pulmonary and systemic inflammation. A more intense ‘cytokine storm’ is postulated as the mechanism behind the extreme immune response seen in severe COVID-19. It is striking how dangerous the combination of obesity and COVID-19 is, resulting in a greater risk of ICU admission and a higher mortality. Furthermore, patients from a BAME background appear to have increased mortality after SARS-CoV-2 infection; they also have a higher prevalence of central obesity and its metabolic complications. In the absence of an effective vaccine, the therapeutic potential of immune-modulating drugs is a priority, but the development of new drugs is expensive and time-consuming. A more pragmatic solution would be to seek to repurpose existing drugs, particularly those that might suppress the heightened cytokine activity seen in obesity, the major risk factor for a poor prognosis in COVID-19. Montelukast is a cysteinyl leukotriene receptor antagonist licensed to treat asthma and allergic rhinitis. It has been shown to diminish pulmonary response to antigen, tissue eosinophilia and IL-5 expression in inflammatory cells. It has also been shown to decrease elevated levels of IL-1β and IL8 in humans with viral upper respiratory tract infections compared with placebo-treated patients. In addition, in silico studies have demonstrated a high binding affinity of the montelukast molecule to the terminal site of the virus’s main protease enzyme which is needed for virus RNA synthesis and replication. Montelukast, which is cheap, safe and widely available would appear to have the potential to be an ideal candidate drug for clinical trials, particularly in early stage disease before irreparable tissue damage has already occurred. Hypothesis Through a direct anti-viral effect, or by suppression of heightened cytokine release in response to SARS-CoV-2, montelukast will reduce the severity of immune-mediated multiorgan damage resulting from COVID-19, particularly in patients with central obesity and metabolic syndrome.
Keywords	covid19
Subject code	610
Publishing date	2020-05-25
Publisher	Elsevier
Publishing country	uk
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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