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COVID-19, Diabetes, Obesity and Cardiometabolic Alterations: Recent Findings and Future Perspectives

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 28352

Special Issue Editors


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Guest Editor
Department of Internal Medicine and Medical Specialties (DIMIS), Università degli Studi di Palermo UNIPA, 90100 Palermo, Italy
Interests: cardiovascular risk; lipids; diabetes; prevention; therapy; metabolic syndrome; metabolism; lipoproteins; incretins; nutraceuticals
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Guest Editor
Clinical Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia
Interests: diabetes; metabolic diseases

Special Issue Information

Dear Colleagues, 

We have been facing a terrible pandemic now for almost 2 years, due to the emergence of what was then the new coronavirus, responsible for COVID-19. Globally, the impact of this pandemic remains serious, changing our daily life as well as the usual care of patients. In different geographical areas (including Asia, Europe, North and South America, North and South Africa, as well as in Australia), patients with diabetes, obesity, and cardiovascular diseases are shown to be those at higher risk of the most serious forms of COVID-19 and their related mortality. We have learnt so many lessons about COVID-19 and its complications during the last two years, which have paved the way for better management of patients with this new disease. With this Special Issue, we aim to provide an updated contribution to the scientific and medical community about the close relationships between diabetes, obesity, cardiovascular diseases and COVID-19. We therefore encourage the submission of molecular biology articles dealing with the current knowledge on this topic as well as those with perspectives for the future.

We welcome submissions to this special issue which focus on molecular level, purely clinical papers are discouraged.

Dr. Manfredi Rizzo
Dr. Andrej Janež
Dr. Ali Abbas Rizvi
Guest Editors

Manuscript Submission Information

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Keywords

  • diabetes
  • cardiovascular
  • obesity risk
  • COVID-19 prevention and therapy

Published Papers (7 papers)

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Editorial

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4 pages, 203 KiB  
Editorial
Cardiometabolic Alterations in the Interplay of COVID-19 and Diabetes: Current Knowledge and Future Avenues
by Ali A. Rizvi, Andrej Janez and Manfredi Rizzo
Int. J. Mol. Sci. 2021, 22(22), 12311; https://doi.org/10.3390/ijms222212311 - 15 Nov 2021
Cited by 8 | Viewed by 1673
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) pandemic has raged for almost two years, with few signs of a sustained abatement or remission [...] Full article

Research

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10 pages, 991 KiB  
Article
Decreased Gas6 and sAxl Plasma Levels Are Associated with Hair Loss in COVID-19 Survivors
by Daria Apostolo, Davide D’Onghia, Stelvio Tonello, Rosalba Minisini, Alessio Baricich, Carla Gramaglia, Filippo Patrucco, Patrizia Zeppegno, Antonio Acquaviva, Piero Emilio Balbo, Luigi Mario Castello, Giuseppe Cappellano, Annalisa Chiocchetti, Chiara Gerevini, Mara Giordano, Fatiha Laaguid, Marcello Manfredi, Davide Raineri, Cristina Rigamonti, Roberta Rolla, Valentina Romano, Marco Confalonieri, Paola Savoia, Elisa Zavattaro, Mario Pirisi, Barbara Ruaro, Pier Paolo Sainaghi and Mattia Bellanadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2023, 24(7), 6257; https://doi.org/10.3390/ijms24076257 - 26 Mar 2023
Cited by 7 | Viewed by 3853
Abstract
Post-acute conditions after coronavirus disease 2019 (COVID-19) are quite common, although the underlying pathogenetic mechanisms leading to these conditions are not yet completely understood. In this prospective observational study, we aimed to test the hypothesis that Growth Arrest-Specific 6 (Gas6) and its soluble [...] Read more.
Post-acute conditions after coronavirus disease 2019 (COVID-19) are quite common, although the underlying pathogenetic mechanisms leading to these conditions are not yet completely understood. In this prospective observational study, we aimed to test the hypothesis that Growth Arrest-Specific 6 (Gas6) and its soluble receptors, Axl (sAxl) and MerTK (sMer), might be implicated. A total of 263 subjects underwent a structured clinical evaluation one year after their hospital discharge for COVID-19, and they consented to donate a blood sample to measure their circulating Gas6, sAxl, and sMer levels. A total of 98 (37.3%) post-COVID-19 subjects complained of at least one residual physical symptom one year after their hospital discharge. Univariate analysis revealed that sAxl was marginally associated with residual symptoms, but at the level of logistic regression analysis, only the diffusing capacity of the lungs for carbon monoxide (DLCO) (OR 0.98, CI 95%: 0.96–0.99; p = 0.007) and the female sex (OR 2.49, CI 95%: 1.45–4.28; p = 0.001) were independently associated with long-lasting symptoms. A total of 69 (26.2%) subjects had hair loss. At the level of univariate analysis, Gas6, sAxl, DLCO, and the female gender were associated with its development. In a logistic regression analysis model, Gas6 (OR 0.96, CI 95%: 0.92–0.99; p = 0.015) and sAxl (OR 0.98, CI 95%; 0.97–1.0; p = 0.014), along with the female sex (OR 6.58, CI 95%: 3.39–12.78; p = 0.0001), were independent predictors of hair loss. Decreased levels of Gas6 and sAxl were associated with a history of hair loss following COVID-19. This was resolved spontaneously in most patients, although 23.7% complained of persistent hair loss one year after hospital discharge. Full article
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24 pages, 4739 KiB  
Article
SARS-CoV-2 S Mutations: A Lesson from the Viral World to Understand How Human Furin Works
by Leonardo Cassari, Angela Pavan, Giulia Zoia, Monica Chinellato, Elena Zeni, Alessandro Grinzato, Sylvia Rothenberger, Laura Cendron, Monica Dettin and Antonella Pasquato
Int. J. Mol. Sci. 2023, 24(5), 4791; https://doi.org/10.3390/ijms24054791 - 1 Mar 2023
Cited by 3 | Viewed by 2486
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the etiological agent responsible for the worldwide pandemic and has now claimed millions of lives. The virus combines several unusual characteristics and an extraordinary ability to spread among humans. In particular, the dependence of the maturation [...] Read more.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the etiological agent responsible for the worldwide pandemic and has now claimed millions of lives. The virus combines several unusual characteristics and an extraordinary ability to spread among humans. In particular, the dependence of the maturation of the envelope glycoprotein S from Furin enables the invasion and replication of the virus virtually within the entire body, since this cellular protease is ubiquitously expressed. Here, we analyzed the naturally occurring variation of the amino acids sequence around the cleavage site of S. We found that the virus grossly mutates preferentially at P positions, resulting in single residue replacements that associate with gain-of-function phenotypes in specific conditions. Interestingly, some combinations of amino acids are absent, despite the evidence supporting some cleavability of the respective synthetic surrogates. In any case, the polybasic signature is maintained and, as a consequence, Furin dependence is preserved. Thus, no escape variants to Furin are observed in the population. Overall, the SARS-CoV-2 system per se represents an outstanding example of the evolution of substrate–enzyme interaction, demonstrating a fast-tracked optimization of a protein stretch towards the Furin catalytic pocket. Ultimately, these data disclose important information for the development of drugs targeting Furin and Furin-dependent pathogens. Full article
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12 pages, 584 KiB  
Communication
Dyslipidemia and Inflammation as Hallmarks of Oxidative Stress in COVID-19: A Follow-Up Study
by Álvaro Aparisi, Marta Martín-Fernández, Cristina Ybarra-Falcón, José Francisco Gil, Manuel Carrasco-Moraleja, Pedro Martínez-Paz, Iván Cusácovich, Hugo Gonzalo-Benito, Raúl Fuertes, Marta Marcos-Mangas, Carolina Iglesias-Echeverría, J. Alberto San Román, Eduardo Tamayo, David Andaluz-Ojeda and Álvaro Tamayo-Velasco
Int. J. Mol. Sci. 2022, 23(23), 15350; https://doi.org/10.3390/ijms232315350 - 5 Dec 2022
Cited by 8 | Viewed by 2518
Abstract
Recent works have demonstrated a significant reduction in cholesterol levels and increased oxidative stress in patients with coronavirus disease 2019 (COVID-19). The cause of this alteration is not well known. This study aimed to comprehensively evaluate their possible association during the evolution of [...] Read more.
Recent works have demonstrated a significant reduction in cholesterol levels and increased oxidative stress in patients with coronavirus disease 2019 (COVID-19). The cause of this alteration is not well known. This study aimed to comprehensively evaluate their possible association during the evolution of COVID-19. This is an observational prospective study. The primary endpoint was to analyze the association between lipid peroxidation, lipid, and inflammatory profiles in COVID-19 patients. A multivariate regression analysis was employed. The secondary endpoint included the long-term follow-up of lipid profiles. COVID-19 patients presented significantly lower values in their lipid profile (total, low, and high-density lipoprotein cholesterol) with greater oxidative stress and inflammatory response compared to the healthy controls. Lipid peroxidation was the unique oxidative parameter with a significant association with the total cholesterol (OR: 0.982; 95% CI: 0.969–0.996; p = 0.012), IL1-RA (OR: 0.999; 95% CI: 0.998–0.999; p = 0.021) IL-6 (OR: 1.062; 95% CI: 1.017–1.110; p = 0.007), IL-7 (OR: 0.653; 95% CI: 0.433–0.986; p = 0.042) and IL-17 (OR: 1.098; 95% CI: 1.010–1.193; p = 0.028). Lipid abnormalities recovered after the initial insult during long-term follow-up (IQR 514 days); however, those with high LPO levels at hospital admission had, during long-term follow-up, an atherogenic lipid profile. Our study suggests that oxidative stress in COVID-19 is associated with derangements of the lipid profile and inflammation. Survivors experienced a recovery in their lipid profiles during long-term follow-up, but those with stronger oxidative responses had an atherogenic lipid profile. Full article
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Review

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13 pages, 1388 KiB  
Review
Associations of Dynapenic Obesity and Sarcopenic Obesity with the Risk of Complications in COVID-19
by Laura Pérez-Campos Mayoral, Carlos Alberto Matias-Cervantes, Eduardo Pérez-Campos, Carlos Romero Díaz, Luis Ángel Laguna Barrios, María del Socorro Pina Canseco, Margarito Martínez Cruz, Eduardo Pérez-Campos Mayoral, Carlos Josué Solórzano Mata, Francisco Javier Rodal Canales, Héctor Martínez Ruíz and María Teresa Hernández-Huerta
Int. J. Mol. Sci. 2022, 23(15), 8277; https://doi.org/10.3390/ijms23158277 - 27 Jul 2022
Cited by 5 | Viewed by 3532
Abstract
Ageing is associated with changes in body composition, such as low muscle mass (sarcopenia), decreased grip strength or physical function (dynapenia), and accumulation of fat mass. When the accumulation of fat mass synergistically accompanies low muscle mass or reduced grip strength, it results [...] Read more.
Ageing is associated with changes in body composition, such as low muscle mass (sarcopenia), decreased grip strength or physical function (dynapenia), and accumulation of fat mass. When the accumulation of fat mass synergistically accompanies low muscle mass or reduced grip strength, it results in sarcopenic obesity and dynapenic obesity, respectively. These types of obesity contribute to the increased risk of cardiovascular disease and mortality in the elderly, which could increase the damage caused by COVID-19. In this review, we associated factors that could generate a higher risk of COVID-19 complications in dynapenic obesity and sarcopenic obesity. For example, skeletal muscle regulates the expression of inflammatory cytokines and supports metabolic stress in pulmonary disease; hence, the presence of dynapenic obesity or sarcopenic obesity could be related to a poor prognosis in COVID-19 patients. Full article
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14 pages, 341 KiB  
Review
Consequences of COVID-19 for the Pancreas
by Urszula Abramczyk, Maciej Nowaczyński, Adam Słomczyński, Piotr Wojnicz, Piotr Zatyka and Aleksandra Kuzan
Int. J. Mol. Sci. 2022, 23(2), 864; https://doi.org/10.3390/ijms23020864 - 13 Jan 2022
Cited by 31 | Viewed by 8545
Abstract
Although coronavirus disease 2019 (COVID-19)-related major health consequences involve the lungs, a growing body of evidence indicates that COVID-19 is not inert to the pancreas either. This review presents a summary of the molecular mechanisms involved in the development of pancreatic dysfunction during [...] Read more.
Although coronavirus disease 2019 (COVID-19)-related major health consequences involve the lungs, a growing body of evidence indicates that COVID-19 is not inert to the pancreas either. This review presents a summary of the molecular mechanisms involved in the development of pancreatic dysfunction during the course of COVID-19, the comparison of the effects of non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pancreatic function, and a summary of how drugs used in COVID-19 treatment may affect this organ. It appears that diabetes is not only a condition that predisposes a patient to suffer from more severe COVID-19, but it may also develop as a consequence of infection with this virus. Some SARS-CoV-2 inpatients experience acute pancreatitis due to direct infection of the tissue with the virus or due to systemic multiple organ dysfunction syndrome (MODS) accompanied by elevated levels of amylase and lipase. There are also reports that reveal a relationship between the development and treatment of pancreatic cancer and SARS-CoV-2 infection. It has been postulated that evaluation of pancreatic function should be increased in post-COVID-19 patients, both adults and children. Full article
12 pages, 865 KiB  
Review
The Role of Endothelium in COVID-19
by Mihaela Ionescu, Anca Pantea Stoian, Manfredi Rizzo, Dragos Serban, Domenico Nuzzo, Laura Mazilu, Andra Iulia Suceveanu, Ana Maria Dascalu and Irinel Raluca Parepa
Int. J. Mol. Sci. 2021, 22(21), 11920; https://doi.org/10.3390/ijms222111920 - 3 Nov 2021
Cited by 28 | Viewed by 4257
Abstract
The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the [...] Read more.
The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin–angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection. Full article
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