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1.
Biochimie ; 179: 247-256, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1326923

ABSTRACT

Viruses, including the novel coronavirus SARS-CoV-2, redirect infected cell metabolism to their own purposes. After binding to its receptor angiotensin-converting enzyme 2 (ACE2) on the cell surface, the SARS-CoV-2 is taken up by receptor-mediated endocytosis ending in the acidic endolysosomal compartment. The virus hijacks the endosomal machinery leading to fusion of viral and endosomal membranes and release of the viral RNA into the cytosol. This mini-review specifically highlights the membrane lipid organization of the endosomal system focusing on the unconventional and late endosome/lysosome-specific phospholipid, bis(monoacylglycero)phosphate (BMP). BMP is enriched in alveolar macrophages of lung, one of the target tissue of SARS-CoV-2. This review details the BMP structure, its unsaturated fatty acid composition and fusogenic properties that are essential for the highly dynamic formation of the intraluminal vesicles inside the endosomes. Interestingly, BMP is necessary for infection and replication of enveloped RNA virus such as SARS-CoV-1 and Dengue virus. We also emphasize the role of BMP in lipid sorting and degradation, especially cholesterol transport in cooperation with Niemann Pick type C proteins (NPC 1 and 2) and with some oxysterol-binding protein (OSBP)-related proteins (ORPs) as well as in sphingolipid degradation. Interestingly, numerous virus infection required NPC1 as well as ORPs along the endocytic pathway. Furthermore, BMP content is increased during pathological endosomal lipid accumulation in various lysosomal storage disorders. This is particularly important knowing the high percentage of patients with metabolic disorders among the SARS-CoV-2 infected patients presenting severe forms of COVID-19.


Subject(s)
Endocytosis , Host Microbial Interactions , Lysophospholipids/metabolism , Monoglycerides/metabolism , SARS-CoV-2/physiology , Cholesterol/metabolism , Homeostasis , Humans
2.
J Am Heart Assoc ; 10(12): e018451, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1259045

ABSTRACT

Background Although chronic cardio-metabolic disease is a common comorbidity among patients with COVID-19, its effects on the clinical characteristics and outcome are not well known. Methods and Results This study aimed to explore the association between underlying cardio-metabolic disease and mortality with COVID-19 among hospitalized patients. This multicenter, retrospective, and real-world study was conducted from January 22, 2020 to March 25, 2020 in China. Data between patients with and without 5 main cardio-metabolic diseases including hypertension, diabetes mellitus, coronary heart disease, cerebrovascular disease, and hyperlipidemia were compared. A total of 1303 hospitalized patients were included in the final analysis. Of them, 520 patients (39.9%) had cardio-metabolic disease. Compared with patients without cardio-metabolic disease, more patients with cardio-metabolic disease had COVID-related complications including acute respiratory distress syndrome (9.81% versus 3.32%; P<0.001), acute kidney injury (4.23% versus 1.40%; P=0.001), secondary infection (13.9% versus 9.8%; P=0.026), hypoproteinemia (12.1% versus 5.75%; P<0.001), and coagulopathy (19.4% versus 10.3%; P<0.001), had higher incidences of the severe type of COVID-19 (32.9% versus 16.7%; P<0.001), more were admitted to the intensive care unit (11.7% versus 7.92%; P=0.021), and required mechanical ventilation (9.8% versus 4.3%; P<0.001). When the number of the patients' cardio-metabolic diseases was 0, 1, and >2, the mortality was 4.2%, 11.1%, and 19.8%, respectively. The multivariable-adjusted hazard ratio of mortality among patients with cardio-metabolic disease was 1.80 (95% CI, 1.17-2.77). Conclusions Cardio-metabolic disease was a common condition among hospitalized patients with COVID-19, and it was associated with higher risks of in-hospital mortality.


Subject(s)
COVID-19/complications , Hospitalization , Metabolic Syndrome/complications , Adult , Aged , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , China , Chronic Disease , Comorbidity , Disease Progression , Female , Hospital Mortality , Humans , Incidence , Male , Metabolic Syndrome/diagnosis , Metabolic Syndrome/mortality , Metabolic Syndrome/therapy , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Time Factors
3.
Adv Exp Med Biol ; 1318: 333-341, 2021.
Article in English | MEDLINE | ID: covidwho-1222722

ABSTRACT

COVID-19 is a newly emerging pandemic caused by a novel coronavirus. After its first report in China in December 2019, the disease already spread and affected more than 200 countries worldwide. It correlates with different phenotypes ranging from an acute febrile illness to severe respiratory problems. Often, patients with COVID-19 suffer from metabolic disorders, and this can result in a more severe clinical course. COVID-19 might also co-occur with other common diseases in different settings. In tropical countries, COVID-19 has already affected thousands of local populations. Tropical diseases such as dengue and tuberculosis can modify the clinical presentation of COVID-19 and result in difficulty in the diagnosis and treatment of the patients. The complexity of concurrence between COVID-19 and tropical diseases is, thus, a matter of concern in tropical medicine. This chapter is devoted to discussing problems surrounding the management of COVID-19 in tropical countries. To exemplify the effects of COVID-19 on tropical countries, the authors would show how COVID-19 has affected Indochina, a large tropical area.


Subject(s)
COVID-19 , China/epidemiology , Fever , Humans , Pandemics , SARS-CoV-2 , Tropical Climate
4.
Int J Mol Sci ; 22(8)2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1196033

ABSTRACT

Amyloidoses are a group of diseases associated with the formation of pathological protein fibrils with cross-ß structures. Approximately 5-10% of the cases of these diseases are determined by amyloidogenic mutations, as well as by transmission of infectious amyloids (prions) between organisms. The most common group of so-called sporadic amyloidoses is associated with abnormal aggregation of wild-type proteins. Some sporadic amyloidoses are known to be induced only against the background of certain pathologies, but in some cases the cause of amyloidosis is unclear. It is assumed that these diseases often occur by accident. Here we present facts and hypotheses about the association of sporadic amyloidoses with vascular pathologies, trauma, oxidative stress, cancer, metabolic diseases, chronic infections and COVID-19. Generalization of current data shows that all sporadic amyloidoses can be regarded as a secondary event occurring against the background of diseases provoking a cellular stress response. Various factors causing the stress response provoke protein overproduction, a local increase in the concentration or modifications, which contributes to amyloidogenesis. Progress in the treatment of vascular, metabolic and infectious diseases, as well as cancers, should lead to a significant reduction in the risk of sporadic amyloidoses.


Subject(s)
Amyloidosis/etiology , Stress, Physiological , Brain Injuries/complications , Communicable Diseases/complications , Humans , Metabolic Diseases/complications , Neoplasms/complications , Oxidative Stress , Vascular Diseases/complications
5.
Dig Liver Dis ; 53(5): 525-533, 2021 05.
Article in English | MEDLINE | ID: covidwho-1062311

ABSTRACT

BACKGROUND: Metabolic diseases are risk factors for severe Coronavirus disease (COVID-19), which have a close relationship with metabolic dysfunction-associated fatty liver disease (MAFLD). AIMS: To evaluate the presence of MAFLD and fibrosis in patients with COVID-19 and its association with prognosis. METHODS: Retrospective cohort study. In hospitalized patients with COVID-19, the presence of liver steatosis was determined by computed tomography scan (CT). Liver fibrosis was assessed using the NAFLD fibrosis score (NFS score), and when altered, the AST to platelet ratio index (APRI) score. Mann-Whitney U, Student´s t-test, logistic regression analysis, Kaplan-Meier curves and Cox regression analysis were used. RESULTS: 432 patients were analyzed, finding steatosis in 40.6%. No differences in pulmonary involvement on CT scan, treatment, or number of days between the onset of symptoms and hospital admission were found between patients with and without MAFLD. The presence of liver fibrosis was associated with higher severity scores, higher levels of inflammatory markers, requirement of mechanical ventilation, incidence of acute kidney injury (AKI), and higher mortality than patients without fibrosis. CONCLUSION: The presence of fibrosis rather than the presence of MAFLD is associated with increased risk for mechanical ventilation, development of AKI, and higher mortality in COVID-19 patients.


Subject(s)
COVID-19 , Fatty Liver , Liver Cirrhosis , Liver , Respiration, Artificial/statistics & numerical data , Aspartate Aminotransferases/blood , Biomarkers/blood , Blood Platelets/pathology , COVID-19/blood , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Fatty Liver/diagnosis , Fatty Liver/epidemiology , Fatty Liver/metabolism , Female , Humans , Liver/diagnostic imaging , Liver/metabolism , Liver/pathology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Cirrhosis/metabolism , Liver Function Tests/methods , Male , Mexico/epidemiology , Middle Aged , Prognosis , Research Design , Retrospective Studies , Risk Factors , Severity of Illness Index , Tomography, X-Ray Computed/methods
6.
Nutrition ; 81: 111016, 2021 01.
Article in English | MEDLINE | ID: covidwho-1036324

ABSTRACT

The world is currently facing the coronavirus disease (COVID-19) pandemic which places great pressure on health care systems and workers, often presents with severe clinical features, and sometimes requires admission into intensive care units. Derangements in nutritional status, both for obesity and malnutrition, are relevant for the clinical outcome in acute illness. Systemic inflammation, immune system impairment, sarcopenia, and preexisting associated conditions, such as respiratory, cardiovascular, and metabolic diseases related to obesity, could act as crucial factors linking nutritional status and the course and outcome of COVID-19. Nevertheless, vitamins and trace elements play an essential role in modulating immune response and inflammatory status. Overall, evaluation of the patient's nutritional status is not negligible for its implications on susceptibility, course, severity, and responsiveness to therapies, in order to perform a tailored nutritional intervention as an integral part of the treatment of patients with COVID-19. The aim of this study was to review the current data on the relevance of nutritional status, including trace elements and vitamin status, in influencing the course and outcome of the disease 3 mo after the World Health Organization's declaration of COVID-19 as a pandemic.


Subject(s)
COVID-19/complications , Malnutrition/complications , Obesity/complications , Trace Elements/deficiency , COVID-19/epidemiology , COVID-19/immunology , Cardiovascular Diseases/complications , Cardiovascular Diseases/etiology , Humans , Inflammation/complications , Nutritional Status , Pandemics , Respiratory Tract Diseases/etiology , Respiratory Tract Diseases/immunology , Respiratory Tract Diseases/physiopathology , SARS-CoV-2/physiology , Sarcopenia/complications , Virus Replication
7.
J Cardiothorac Vasc Anesth ; 35(7): 1999-2006, 2021 07.
Article in English | MEDLINE | ID: covidwho-1035929

ABSTRACT

OBJECTIVES: The authors evaluated the outcome of adult patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) requiring the use of extracorporeal membrane oxygenation (ECMO). DESIGN: Multicenter retrospective, observational study. SETTING: Ten tertiary referral university and community hospitals. PARTICIPANTS: Patients with confirmed severe COVID-19-related ARDS. INTERVENTIONS: Venovenous or venoarterial ECMO. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-two patients (mean age 51.1 ± 9.7 years, female 17.4%) were treated with ECMO for confirmed severe COVID-19-related ARDS. Before ECMO, the mean Sequential Organ Failure Assessment score was 10.1 ± 4.4, mean pH was 7.23 ± 0.09, and mean PaO2/fraction of inspired oxygen ratio was 77 ± 50 mmHg. Venovenous ECMO was adopted in 122 patients (92.4%) and venoarterial ECMO in ten patients (7.6%) (mean duration, 14.6 ± 11.0 days). Sixty-three (47.7%) patients died on ECMO and 70 (53.0%) during the index hospitalization. Six-month all-cause mortality was 53.0%. Advanced age (per year, hazard ratio [HR] 1.026, 95% CI 1.000-1-052) and low arterial pH (per unit, HR 0.006, 95% CI 0.000-0.083) before ECMO were the only baseline variables associated with increased risk of six-month mortality. CONCLUSIONS: The present findings suggested that about half of adult patients with severe COVID-19-related ARDS can be managed successfully with ECMO with sustained results at six months. Decreased arterial pH before ECMO was associated significantly with early mortality. Therefore, the authors hypothesized that initiation of ECMO therapy before severe metabolic derangements subset may improve survival rates significantly in these patients. These results should be viewed in the light of a strict patient selection policy and may not be replicated in patients with advanced age or multiple comorbidities. CLINICAL TRIAL REGISTRATION: identifier, NCT04383678.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Adult , Female , Humans , Middle Aged , Respiratory Distress Syndrome/therapy , Retrospective Studies , SARS-CoV-2
8.
Nutrition ; 81: 111016, 2021 01.
Article in English | MEDLINE | ID: covidwho-997375

ABSTRACT

The world is currently facing the coronavirus disease (COVID-19) pandemic which places great pressure on health care systems and workers, often presents with severe clinical features, and sometimes requires admission into intensive care units. Derangements in nutritional status, both for obesity and malnutrition, are relevant for the clinical outcome in acute illness. Systemic inflammation, immune system impairment, sarcopenia, and preexisting associated conditions, such as respiratory, cardiovascular, and metabolic diseases related to obesity, could act as crucial factors linking nutritional status and the course and outcome of COVID-19. Nevertheless, vitamins and trace elements play an essential role in modulating immune response and inflammatory status. Overall, evaluation of the patient's nutritional status is not negligible for its implications on susceptibility, course, severity, and responsiveness to therapies, in order to perform a tailored nutritional intervention as an integral part of the treatment of patients with COVID-19. The aim of this study was to review the current data on the relevance of nutritional status, including trace elements and vitamin status, in influencing the course and outcome of the disease 3 mo after the World Health Organization's declaration of COVID-19 as a pandemic.


Subject(s)
COVID-19/complications , Malnutrition/complications , Obesity/complications , Trace Elements/deficiency , COVID-19/epidemiology , COVID-19/immunology , Cardiovascular Diseases/complications , Cardiovascular Diseases/etiology , Humans , Inflammation/complications , Nutritional Status , Pandemics , Respiratory Tract Diseases/etiology , Respiratory Tract Diseases/immunology , Respiratory Tract Diseases/physiopathology , SARS-CoV-2/physiology , Sarcopenia/complications , Virus Replication
9.
Diabetes Metab Syndr Obes ; 13: 4953-4959, 2020.
Article in English | MEDLINE | ID: covidwho-992955

ABSTRACT

The growing prevalence of overweight and obesity has been a worldwide public health issue. During the COVID-19 pandemic, obesity is associated with a higher risk of severity and a worse clinical outcome of SARS-COV-2 infection. This may be because of the chronic low-grade inflammation, impaired immune response and metabolic disorders in obese patients. In this narrative review, we have summarized the association between obesity and COVID-19 and discussed the potential pathogenesis and treatment in these patients. This work may provide practical suggestions on the clinical management of obese COVID-19 patients.

10.
J Sports Med Phys Fitness ; 61(11): 1538-1547, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-970965

ABSTRACT

Many reports showed a dramatic decrease in the levels of physical activity during the current pandemic of SARS-CoV-2. This has substantial immune and metabolic implications, especially in those at risk or with metabolic diseases including individuals with obesity and Type 2 diabetes. In this study we discussed the route from physical inactivity to immune and metabolic aberrancies; focusing on how insulin resistance could represent an adaptive mechanism to the low physical activity levels and on how such an adaptive mechanism could shift to a pathognomonic feature of metabolic diseases, creating a vicious circle of immune and metabolic aberrancies. We provide a theoretical framework to the severe immunopathology of COVID-19 in patients with metabolic diseases. We finally discuss the idea of exercise as a potential adjuvant against COVID-19 and emphasize how even interrupting prolonged periods of sitting with short time breaks of very light activity could be a feasible strategy to limit the deleterious effects of the outbreak.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Exercise , Humans , Obesity/epidemiology , SARS-CoV-2 , Sedentary Behavior
11.
Pharmacol Ther ; 222: 107794, 2021 06.
Article in English | MEDLINE | ID: covidwho-968657

ABSTRACT

Obesity and the metabolic syndrome (MetS), which have reached pandemic proportions significantly increase the risk for type 2 diabetes, cardiovascular disease, and other serious conditions. Recent data with COVID-19 patients indicate that obesity also is a significant risk factor for this novel viral disease and poor outcome of associated critical illness. These findings considerably change the view of obesity as a driver of serious, but slowly-progressing chronic diseases, and emphasize the urgency to explore new therapeutic approaches. Inflammation is a recognized driver of metabolic derangements in obesity and MetS, and a core feature of COVID-19 pathobiology. Recent advances in our understanding of inflammatory regulation have highlighted the role of the nervous system and the vagus nerve-based inflammatory reflex. Current bioelectronic and pharmacological therapeutic explorations centered on the inflammatory reflex offer new approaches for conditions characterized by immune and metabolic dysregulation and for ameliorating the escalating burden of obesity, MetS, and COVID-19.


Subject(s)
COVID-19 , Inflammation , Obesity , Vagus Nerve/immunology , COVID-19/immunology , COVID-19/metabolism , Humans , Inflammation/immunology , Inflammation/metabolism , Metabolic Syndrome/immunology , Obesity/epidemiology , Obesity/immunology , Obesity/therapy , SARS-CoV-2
12.
Ann Natl Acad Med Sci ; 56(2): 112-115, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-882962

ABSTRACT

COVID-19 has affected millions of people across the world but disproportionately and severely affects persons with metabolic disorders such as obesity, diabetes mellitus and hypertension. In this brief review, we discuss the pathways of immune dysregulation that may lead to severe COVID-19 in persons with metabolic conditions.

13.
Front Med (Lausanne) ; 7: 515, 2020.
Article in English | MEDLINE | ID: covidwho-732885

ABSTRACT

Coronavirus Disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which primarily targets the human respiratory system and may lead to severe pneumonia and ultimately death. Mortality rate is particurlarly high among people beyond the sixth decade of life with cardiovascular and metabolic diseases. The discovery that the SARS-CoV-2 uses the renin-angiotensin system (RAS) component ACE2 as a receptor to invade host epithelial cells and cause organs damage resulted in a debate regarding the role of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) therapies during COVID-19 pandemic. Some authors proposed the discontinuation of ACEIs and ARBs for cardiovascular, kidney, and metabolic diseases, while expert opinions have discouraged that due to limited empirical evidence of their negative effect on COVID-19 outcomes, and that withdrawing treatment may contribute to clinical decompensation in high-risk patients. Moreover, as cardiovascular and metabolic diseases are associated with neurodegenerative and psychiatric disorders, especially among older adults, a critical appraisal of the potential positive effects of ACEIs and ARBs is highly needed. Herein, we aim to discuss the conundrum of ACEIs and ARBs use in high-risk patients for COVID-19, and their potential protective role on the development and/or progression of geriatric neuropsychiatric disorders.

14.
Andrology ; 9(1): 33-38, 2021 01.
Article in English | MEDLINE | ID: covidwho-679523

ABSTRACT

BACKGROUND: A pandemic outbreak of COVID-19 has been sweeping the world since December. It begins as a respiratory infection that, mainly in men with diabetes or renal impairment, evolves into a systemic disease, with SARDS, progressive endothelial cell damage, abnormal clotting and impaired cardiovascular and liver function. Some clinical trials are testing biological drugs to limit the immune system dysregulation, "cytokines storm," that causes the systemic complications of COVID-19. The contraindications of these drugs and their cost raise concerns over the implications of their widespread availability. OBJECTIVES: Numerous clinical and experimental studies have revealed a role for the nitric oxide (NO)-cyclic GMP-phosphodiesterase type 5 (PDE5) pathway in modulating low-grade inflammation in patients with metabolic diseases, offering cardiovascular protection. PDE5 inhibition favors an anti-inflammatory response by modulating activated T cells, reducing cytokine release, lowering fibrosis, increasing oxygen diffusion, stimulating vascular repair. PDE5 is highly expressed in the lungs, where its inhibition improves pulmonary fibrosis, a complication of severe COVID-19 disease. MATERIALS AND METHODS: We performed a systematic review of all evidence documenting any involvement of the NO-cGMP-PDE5 axis in the pathophysiology of COVID-19, presenting the ongoing clinical trials aimed at modulating this axis, including our own "silDEnafil administration in DiAbetic and dysmetaboLic patients with COVID-19 (DEDALO trial)." RESULTS: The reviewed evidence suggests that PDE5 inhibitors could offer a new strategy in managing COVID-19 by (i) counteracting the Ang-II-mediated downregulation of AT-1 receptor; (ii) acting on monocyte switching, thus reducing pro-inflammatory cytokines, interstitial infiltration and the vessel damage responsible for alveolar hemorrhage-necrosis; (iii) inhibiting the transition of endothelial and smooth muscle cells to mesenchymal cells in the pulmonary artery, preventing clotting and thrombotic complications. DISCUSSION AND CONCLUSION: If the ongoing trials presented herein should provide positive findings, the low cost, wide availability and temperature stability of PDE5 inhibitors could make them a major resource to combat COVID-19 in developing countries.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Cyclic GMP/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism , Nitric Oxide/therapeutic use , Phosphodiesterase 5 Inhibitors/therapeutic use , SARS-CoV-2/drug effects , Antiviral Agents/adverse effects , COVID-19/enzymology , COVID-19/virology , Clinical Trials as Topic , Host-Pathogen Interactions , Humans , Molecular Targeted Therapy , Nitric Oxide/adverse effects , Nitric Oxide/metabolism , Phosphodiesterase 5 Inhibitors/adverse effects , SARS-CoV-2/pathogenicity , Signal Transduction , Treatment Outcome
15.
Diabetol Metab Syndr ; 12: 63, 2020.
Article in English | MEDLINE | ID: covidwho-655642

ABSTRACT

Chronic inflammation is involved in the pathogenesis of several metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM). With the recent worldwide outbreak of coronavirus disease (SARS-CoV-2), it has been observed that individuals with these metabolic diseases are more likely to develop complications, increasing the severity of the disease and a poorer outcome. Coronavirus infection leads to the activation of adaptive and innate immune responses, resulting in massive inflammation (to so called cytokine storm), which in turn can lead to damage to various tissues, septic shock and multiple organ failure. Recent evidence suggests that the common link between metabolic diseases and SARS-CoV-2 is the inflammatory response (chronic/low-grade for metabolic diseases and acute/intense in coronavirus infection). However, the ability of the infected individuals to resolve the inflammation has not yet been explored. The heat shock response (HSR), an important anti-inflammatory pathway, is reduced in patients with metabolic diseases and, consequently, may impair inflammation resolution and control in patients with SARS-CoV-2, thus enabling its amplification and propagation through all tissues. Herein, we present a new hypothesis that aims to explain the increased severity of SARS-CoV-2 infection in people with metabolic diseases, and the possible benefits of HSR-inducing therapies to improve the inflammatory profile in these patients.

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