Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 99
Filter
1.
Psychotherapeut (Berl) ; 65(4): 291-296, 2020.
Article in German | MEDLINE | ID: covidwho-1680760

ABSTRACT

Due to the pandemic caused by the coronavirus disease 2019 (COVID-19) and the resulting constraints on personal (i.e. face to face) treatment, video consultations have recently gained a major role in the delivery of healthcare services; however, until now, most psychotherapists have little experience with conducting video consultations, not least because of poor possibilities for reimbursement from the statutory health insurance. This article provides (1) an overview of the effectiveness of psychotherapy interventions delivered via video consultations for depression and anxiety disorders, (2) recommendations for setting up and conducting these consultations and (3) first experiences of psychotherapists from a German feasibility study and from the provision in routine care in hospital during the COVID-19 pandemic.

2.
Dev Neurosci ; 43(3-4): 143-158, 2021.
Article in English | MEDLINE | ID: covidwho-1472320

ABSTRACT

The mechanistic target of rapamycin (mTOR) is a kinase at the center of an evolutionarily conserved signaling pathway that orchestrates cell growth and metabolism. mTOR responds to an array of intra- and extracellular stimuli and in turn controls multiple cellular anabolic and catabolic processes. Aberrant mTOR activity is associated with numerous diseases, with particularly profound impact on the nervous system. mTOR is found in two protein complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which are governed by different upstream regulators and have distinct cellular actions. Mutations in genes encoding for mTOR regulators result in a collection of neurodevelopmental disorders known as mTORopathies. While these disorders can affect multiple organs, neuropsychiatric conditions such as epilepsy, intellectual disability, and autism spectrum disorder have a major impact on quality of life. The neuropsychiatric aspects of mTORopathies have been particularly challenging to treat in a clinical setting. Current therapeutic approaches center on rapamycin and its analogs, drugs that are administered systemically to inhibit mTOR activity. While these drugs show some clinical efficacy, adverse side effects, incomplete suppression of mTOR targets, and lack of specificity for mTORC1 or mTORC2 may limit their utility. An increased understanding of the neurobiology of mTOR and the underlying molecular, cellular, and circuit mechanisms of mTOR-related disorders will facilitate the development of improved therapeutics. Animal models of mTORopathies have helped unravel the consequences of mTOR pathway mutations in specific brain cell types and developmental stages, revealing an array of disease-related phenotypes. In this review, we discuss current progress and potential future directions for the therapeutic treatment of mTORopathies with a focus on findings from genetic mouse models.


Subject(s)
Autism Spectrum Disorder , Animals , Humans , Mechanistic Target of Rapamycin Complex 1/metabolism , Mechanistic Target of Rapamycin Complex 2/metabolism , Mice , Quality of Life , Signal Transduction
3.
Glycobiology ; 31(9): 1080-1092, 2021 09 20.
Article in English | MEDLINE | ID: covidwho-1434394

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), started in 2019 in China and quickly spread into a global pandemic. Nucleocapsid protein (N protein) is highly conserved and is the most abundant protein in coronaviruses and is thus a potential target for both vaccine and point-of-care diagnostics. N Protein has been suggested in the literature as having posttranslational modifications (PTMs), and accurately defining these PTMs is critical for its potential use in medicine. Reports of phosphorylation of N protein have failed to provide detailed site-specific information. We have performed comprehensive glycomics, glycoproteomics and proteomics experiments on two different N protein preparations. Both were expressed in HEK293 cells; one was in-house expressed and purified without a signal peptide (SP) sequence, and the other was commercially produced with a SP channeling it through the secretory pathway. Our results show completely different PTMs on the two N protein preparations. The commercial product contained extensive N- and O-linked glycosylation as well as O-phosphorylation on site Thr393. Conversely, the native N Protein model had O-phosphorylation at Ser176 and no glycosylation, highlighting the importance of knowing the provenance of any commercial protein to be used for scientific or clinical studies. Recent studies have indicated that N protein can serve as an important diagnostic marker for COVID-19 and as a major immunogen by priming protective immune responses. Thus, detailed structural characterization of N protein may provide useful insights for understanding the roles of PTMs on viral pathogenesis, vaccine design and development of point-of-care diagnostics.


Subject(s)
Coronavirus Nucleocapsid Proteins/metabolism , Protein Processing, Post-Translational/physiology , SARS-CoV-2/metabolism , Amino Acid Motifs , Amino Acid Sequence , Binding Sites , Coronavirus Nucleocapsid Proteins/chemistry , Glycosylation , HEK293 Cells , Humans , Phosphorylation , SARS-CoV-2/chemistry
4.
Am J Infect Control ; 49(2): 238-246, 2021 02.
Article in English | MEDLINE | ID: covidwho-1336188

ABSTRACT

INTRODUCTION: On February 11, 2020 WHO designated the name "COVID-19" for the disease caused by "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), a novel virus that quickly turned into a global pandemic. Risks associated with acquiring the virus have been found to most significantly vary by age and presence of underlying comorbidity. In this rapid literature review we explore the prevalence of comorbidities and associated adverse outcomes among individuals with COVID-19 and summarize our findings based on information available as of May 15, 2020. METHODS: A comprehensive systematic search was performed on PubMed, Medline, Scopus, Embase, and Google Scholar to find articles published until May 15, 2020. All relevant articles providing information on PCR tested COVID-19 positive patient population with clinical characteristics and epidemiological information were selected for review and analysis. RESULTS: A total of 27 articles consisting of 22,753 patient cases from major epicenters worldwide were included in the study. Major comorbidities seen in overall population were CVD (8.9%), HTN (27.4%), Diabetes (17.4%), COPD (7.5%), Cancer (3.5%), CKD (2.6%), and other (15.5%). Major comorbidity specific to countries included in the study were China (HTN 39.5%), South Korea (CVD 25.6%), Italy (HTN 35.9%), USA (HTN 38.9%), Mexico, (Other 42.3%), UK (HTN 27.8%), Iran (Diabetes 35.0%). Within fatal cases, an estimated 84.1% had presence of one or more comorbidity. Subgroup analysis of fatality association with having comorbidity had an estimated OR 0.83, CI [0.60-0.99], p<0.05. CONCLUSIONS: Based on our findings, hypertension followed by diabetes and cardiovascular diseases were the most common comorbidity seen in COVID-19 positive patients across major epicenters world-wide. Although having one or more comorbidity is linked to increased disease severity, no clear association was found between having these risk factors and increased risk of fatality.


Subject(s)
COVID-19/epidemiology , Comorbidity , Global Health/statistics & numerical data , Hypertension/epidemiology , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/virology , Diabetes Mellitus/epidemiology , Diabetes Mellitus/virology , Female , Humans , Hypertension/virology , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/virology , Prevalence , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/virology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/virology , Young Adult
5.
Biochimie ; 179: 257-265, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1326917

ABSTRACT

It is becoming obvious that in addition to aging and various hearth pathologies, excess of body weight, especially obesity is a major risk factor for severity of COVID-19 infection. Intriguingly the receptor for SARS-CoV-2 is ACE2, a member of the angiotensin receptor family that has a relatively large tissue distribution. This observation likely explains the multitude of symptoms that have been described from human patients. The adipose tissue also expresses ACE2, suggesting that adipocytes are potentially infected by SARS-CoV-2. Here we discuss some of the potential contribution of the adipose tissue to the severity of the infection and propose some aspects of obese patients metabolic phenotyping to help stratification of individuals with high risk of severe disease.


Subject(s)
COVID-19/complications , Obesity/complications , Adipose Tissue/pathology , Adipose Tissue/virology , Cytokines/metabolism , Humans , Obesity/metabolism , Obesity/pathology , Prevalence
6.
Int J Clin Pract ; 75(9): e14461, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1297676

ABSTRACT

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is an emerging, fast-spreading, highly mortal and worldwide infectious disease. The pulmonary system was defined as the main target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mortality concept of this disease presented with more severe and systemic disease. The present study investigated the relationship between the patient characteristics at the initial hospital administration and fatality in COVID-19 patients. METHODS: In this retrospective and comparative cohort study, all the 767 hospitalised COVID-19 patients, treated between 18 March and 15 May 2020 in the Covid Clinics of Gulhane Training and Research Hospital in Ankara, Turkey, were evaluated. RESULTS: The fatality rate was significantly increased in patients with any comorbid disease except asthma. The initial laboratory test results indicated highly significant differences according to the patient's outcome. A multifactor logistic regression analysis was performed to calculate the adjusted odds ratios for predicting patient outcomes. Being older than 60 years increased the death risk with an adjusted OR of 7.2 (95% CI: 2.23-23.51; P = .001). The presence of a cancer and the extended duration of intensive care unit treatment were other significant risk factors for nonsurvival. Azithromycin treatment was determined as significantly reduced the death ratio in these patients (P = .002). CONCLUSION: It was revealed that being older than 60 years, presence of a cancer and extended duration of ICU treatment were the major risk factors for predicting fatality rate in hospitalised COVID-19 patients.


Subject(s)
COVID-19 , Pandemics , Cohort Studies , Hospital Mortality , Hospitalization , Hospitals , Humans , Intensive Care Units , Retrospective Studies , SARS-CoV-2 , Tertiary Healthcare
7.
Diabetes Obes Metab ; 23(9): 2183-2188, 2021 09.
Article in English | MEDLINE | ID: covidwho-1276622

ABSTRACT

Obesity is a major risk factor for the development of severe coronavirus disease 2019 (COVID-19) infection and mortality. However, it is not known whether patients with obesity are at a greater risk of developing postacute sequelae of COVID-19 (PASC). In a median follow-up time of 8 months and counting from 30 days following a positive viral test of 2839 patients who did not require intensive care unit admission and survived the acute phase of COVID-19, 1230 (43%) patients required medical diagnostic tests, 1255 (44%) patients underwent hospital admission, and 29 (1%) patients died. Compared with patients with a normal body mass index (BMI), the risk of hospital admission was 28% and 30% higher in patients with moderate and severe obesity, respectively. The need for diagnostic tests to assess different medical problems, compared with patients with normal BMI, was 25% and 39% higher in patients with moderate and severe obesity, respectively. The findings of this study suggest that moderate and severe obesity (BMI ≥ 35 kg/m2 ) are associated with a greater risk of PASC.


Subject(s)
COVID-19 , Body Mass Index , Hospitalization , Humans , Intensive Care Units , Obesity/complications , Obesity/epidemiology , Risk Factors , SARS-CoV-2
8.
Eur J Clin Invest ; 51(12): e13626, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1273086

ABSTRACT

BACKGROUND: Fever-7 is a test evaluating host mRNA expression levels of IFI27, JUP, LAX, HK3, TNIP1, GPAA1 and CTSB in blood able to detect viral infections. This test has been validated mostly in hospital settings. Here we have evaluated Fever-7 to identify the presence of respiratory viral infections in a Community Health Center. METHODS: A prospective study was conducted in the "Servicio de Urgencias de Atención Primaria" in Salamanca, Spain. Patients with clinical signs of respiratory infection and at least one point in the National Early Warning Score were recruited. Fever-7 mRNAs were profiled on a Nanostring nCounter® SPRINT instrument from blood collected upon patient enrolment. Viral diagnosis was performed on nasopharyngeal aspirates (NPAs) using the Biofire-RP2 panel. RESULTS: A respiratory virus was detected in the NPAs of 66 of the 100 patients enrolled. Median National Early Warning Score was 7 in the group with no virus detected and 6.5 in the group with a respiratory viral infection (P > .05). The Fever-7 score yielded an overall AUC of 0.81 to predict a positive viral syndromic test. The optimal operating point for the Fever-7 score yielded a sensitivity of 82% with a specificity of 71%. Multivariate analysis showed that Fever-7 was a robust marker of viral infection independently of age, sex, major comorbidities and disease severity at presentation (OR [CI95%], 3.73 [2.14-6.51], P < .001). CONCLUSIONS: Fever-7 is a promising host immune mRNA signature for the early identification of a respiratory viral infection in the community.


Subject(s)
RNA, Messenger/blood , Respiratory Tract Infections/diagnosis , Virus Diseases/diagnosis , Adaptor Proteins, Vesicular Transport/genetics , Aged , Aged, 80 and over , Cathepsin B/genetics , DNA-Binding Proteins/genetics , Early Warning Score , Female , Gene Expression Profiling , Humans , Male , Membrane Glycoproteins/genetics , Membrane Proteins/genetics , Nasopharynx/virology , Respiratory Tract Infections/blood , Respiratory Tract Infections/genetics , Transcriptome , Virus Diseases/blood , Virus Diseases/genetics , gamma Catenin/genetics
9.
Front Pharmacol ; 12: 666348, 2021.
Article in English | MEDLINE | ID: covidwho-1259361

ABSTRACT

Ivermectin (IVM) and moxidectin (MOX) are used extensively as parasiticides in veterinary medicine. Based on in vitro data, IVM has recently been proposed for the prevention and treatment of COVID-19 infection, a condition for which obesity is a major risk factor. In patients, IVM dosage is based on total body weight and there are no recommendations to adjust dosage in obese patients. The objective of this study was to establish, in a canine model, the influence of obesity on the clearance and steady-state volume of distribution of IVM, MOX, and a third analog, eprinomectin (EPR). An experimental model of obesity in dogs was based on a high calorie diet. IVM, MOX, and EPR were administered intravenously, in combination, to a single group of dogs in two circumstances, during a control period and when body weight had been increased by 50%. In obese dogs, clearance, expressed in absolute values (L/day), was not modified for MOX but was reduced for IVM and EPR, compared to the initial control state. However, when scaled by body weight (L/day/kg), plasma clearance was reduced by 55, 42, and 63%, for IVM, MOX and EPR, respectively. In contrast, the steady-state volume of distribution was markedly increased, in absolute values (L), by obesity. For IVM and MOX, this obese dog model suggests that the maintenance doses in the obese subject should be based on lean body weight rather than total weight. On the other hand, the loading dose, when required, should be based on the total body weight of the obese subject.

10.
Immunopharmacol Immunotoxicol ; 43(3): 259-264, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1238100

ABSTRACT

Coronavirus disease 2019 (COVID-19) is associated with irreversible effects on vital organs, especially the respiratory and cardiac systems. While the immune system plays a key role in the survival of patients to viral infections, in COVID-19, there is a hyperinflammatory immune response evoked by all the immune cells, such as neutrophils, monocytes, and includes release of various cytokines, resulting in an exaggerated immune response, named cytokine storm. This severe, dysregulated immune response causes multi-organ damage, which eventually leads to high mortality. One of the most important components of hypersensitivity is immunoglobulin E (IgE), which plays a major role in susceptibility to respiratory infections and can lead to the activation of mast cells. There is also a negative association between IgE and IFN-α, which can reduce Toll-like receptor (TLR) nine receptor expression and TLR-7 signaling to disrupt IFN production. Moreover, anti-IgE drugs such as omalizumab reduces the severity and duration of COVID-19. In addition to its anti-IgE effect, omalizumab inhibits inflammatory cells such as neutrophils. Hence, blockade of IgE may have clinical utility as an immunotherapy for COVID-19.


Subject(s)
COVID-19/drug therapy , COVID-19/immunology , Omalizumab/therapeutic use , Signal Transduction/drug effects , Humans , Immunoglobulin E/immunology , Interferon-alpha/immunology , Omalizumab/immunology , Signal Transduction/immunology , Toll-Like Receptor 7/immunology
11.
Front Endocrinol (Lausanne) ; 12: 652639, 2021.
Article in English | MEDLINE | ID: covidwho-1231330

ABSTRACT

Obesity has been recognized as an independent risk factor for critical illness and major severity in subjects with coronavirus disease 2019 (COVID-19). The role of fat distribution, particularly visceral fat (often linked to metabolic abnormalities), is still unclear. The adipose tissue represents a direct source of cytokines responsible for the pathological modifications occurring within adipose tissue in obese subjects. Adipokines are a crucial connection between metabolism and immune system: their dysregulation in obesity contributes to chronic low-grade systemic inflammation and metabolic comorbidities. Therefore the increased amount of visceral fat can lead to a proinflammatory phenotypic shift. This review analyzes the interrelation between obesity and COVID-19 severity, as well as the cellular key players and molecular mechanisms implicated in adipose inflammation, investigating if adipose tissue can constitute a reservoir for viral spread, and contribute to immune activation and cytokines storm. Targeting the underlying molecular mechanisms might have therapeutic potential in the management of obesity-related complications in COVID-19 patients.


Subject(s)
COVID-19/complications , Obesity/complications , Abdominal Fat/pathology , Adipose Tissue/pathology , COVID-19/physiopathology , Humans , Inflammation/etiology , Obesity/physiopathology
12.
Glycobiology ; 31(9): 1080-1092, 2021 09 20.
Article in English | MEDLINE | ID: covidwho-1231033

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), started in 2019 in China and quickly spread into a global pandemic. Nucleocapsid protein (N protein) is highly conserved and is the most abundant protein in coronaviruses and is thus a potential target for both vaccine and point-of-care diagnostics. N Protein has been suggested in the literature as having posttranslational modifications (PTMs), and accurately defining these PTMs is critical for its potential use in medicine. Reports of phosphorylation of N protein have failed to provide detailed site-specific information. We have performed comprehensive glycomics, glycoproteomics and proteomics experiments on two different N protein preparations. Both were expressed in HEK293 cells; one was in-house expressed and purified without a signal peptide (SP) sequence, and the other was commercially produced with a SP channeling it through the secretory pathway. Our results show completely different PTMs on the two N protein preparations. The commercial product contained extensive N- and O-linked glycosylation as well as O-phosphorylation on site Thr393. Conversely, the native N Protein model had O-phosphorylation at Ser176 and no glycosylation, highlighting the importance of knowing the provenance of any commercial protein to be used for scientific or clinical studies. Recent studies have indicated that N protein can serve as an important diagnostic marker for COVID-19 and as a major immunogen by priming protective immune responses. Thus, detailed structural characterization of N protein may provide useful insights for understanding the roles of PTMs on viral pathogenesis, vaccine design and development of point-of-care diagnostics.


Subject(s)
Coronavirus Nucleocapsid Proteins/metabolism , Protein Processing, Post-Translational/physiology , SARS-CoV-2/metabolism , Amino Acid Motifs , Amino Acid Sequence , Binding Sites , Coronavirus Nucleocapsid Proteins/chemistry , Glycosylation , HEK293 Cells , Humans , Phosphorylation , SARS-CoV-2/chemistry
13.
Int J Qual Health Care ; 33(1)2021 Mar 16.
Article in English | MEDLINE | ID: covidwho-1228518

ABSTRACT

BACKGROUND: COVID-19 pandemic has had a major impact globally, with older people living in aged care homes suffering high death rates. OBJECTIVES: We aimed to compare the impact of initial government policies on this vulnerable older population between the UK and Australia during the first wave of attack. METHODS: We searched websites of governments in the UK and Australia and media outlets. We examined the key policies including the national lockdown dates and the distribution of some important resources (personal protective equipment and testing) and the effects of these initial policies on the mortality rates in the aged care homes during the first wave of attack of COVID-19. RESULTS: We found that both countries had prioritized resources to hospitals over aged care homes during the first wave of attack. Both countries had lower priority for aged care residents in hospitals (e.g. discharging without testing for COVID-19 or discouraging admissions). However, deaths in aged care homes were 270 times higher in the UK than in Australia as on 7 May 2020 (despite UK having a population only 2.5 times larger than Australia). The lower fatality rate in Australia may have been due to the earlier lockdown strategy when the total daily cases were low in Australia (118) compared to the UK (over 1000), as well as the better community viral testing regime in Australia. CONCLUSION: In conclusion, the public health policy in Australia aimed towards earlier intervention with earlier national lockdown and more viral testing to prevent new cases. This primary prevention could have resulted in more lives being saved. In contrast, the initial policy in the UK focussed mainly on protecting resources for hospitals, and there was a delay in national lockdown intervention and lower viral testing rate, resulting in more lives lost in the aged care sector.


Subject(s)
COVID-19/prevention & control , Health Policy , Homes for the Aged/organization & administration , Australia/epidemiology , COVID-19/epidemiology , England/epidemiology , Hospitalization/statistics & numerical data , Humans , Resource Allocation/methods , Resource Allocation/organization & administration , United Kingdom/epidemiology
14.
Eur Heart J Case Rep ; 5(1): ytaa563, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1228481

ABSTRACT

BACKGROUND: The venous thromboembolism (VTE) is a frequent condition, which may worsen the prognosis of hospitalized COVID-19 patients. Nevertheless, the incidence of this complication is unknown in patients with mild COVID-19 symptoms. CASE SUMMARY: A 26-year-old female nurse, who had been taking oral contraceptive pills (OCPs) treatment for the last 2 years, developed mild COVID-19 symptoms (rhinitis and anosmia). She underwent isolation at home and was subsequently followed up with telehealth visits. Fifteen days after her initial presentation, she developed acute onset sudden dyspnoea. On physical examination, she was found to be tachycardic with normal pulse oximetry. The initial risk score for VTE was moderate and laboratory results showed increased D-dimer level without other relevant findings. Computed tomography pulmonary angiography was performed, which confirmed low-risk subsegmental pulmonary embolism. DISCUSSION: Venous thromboembolism in patients who present with severe COVID-19 symptoms has already been described in the literature; its incidence is greater in patients hospitalized in intensive care units. Efforts to prevent VTE based on risk scores are widely recognized. However, the relationship in patients who present with mild COVID-19 symptoms and VTE is still unknown. Recently, experts on this field have introduced thromboprophylaxis guidelines including ambulatory patients based on the severity of COVID-19 symptoms and pro-thrombotic risk. Our patient showed no major risk for developing VTE; therefore, the VTE could be associated with SARS-CoV-2 infection or the eventual pro-thrombotic association with the concomitant use of OCPs.

15.
Molecules ; 26(10)2021 May 11.
Article in English | MEDLINE | ID: covidwho-1224076

ABSTRACT

Resveratrol is a phytoalexin produced by many plants as a defense mechanism against stress-inducing conditions. The richest dietary sources of resveratrol are berries and grapes, their juices and wines. Good bioavailability of resveratrol is not reflected in its high biological activity in vivo because of resveratrol isomerization and its poor solubility in aqueous solutions. Proteins, cyclodextrins and nanomaterials have been explored as innovative delivery vehicles for resveratrol to overcome this limitation. Numerous in vitro and in vivo studies demonstrated beneficial effects of resveratrol in cardiovascular diseases (CVD). Main beneficial effects of resveratrol intake are cardioprotective, anti-hypertensive, vasodilatory, anti-diabetic, and improvement of lipid status. As resveratrol can alleviate the numerous factors associated with CVD, it has potential as a functional supplement to reduce COVID-19 illness severity in patients displaying poor prognosis due to cardio-vascular complications. Resveratrol was shown to mitigate the major pathways involved in the pathogenesis of SARS-CoV-2 including regulation of the renin-angiotensin system and expression of angiotensin-converting enzyme 2, stimulation of immune system and downregulation of pro-inflammatory cytokine release. Therefore, several studies already have anticipated potential implementation of resveratrol in COVID-19 treatment. Regular intake of a resveratrol rich diet, or resveratrol-based complementary medicaments, may contribute to a healthier cardio-vascular system, prevention and control of CVD, including COVID-19 disease related complications of CVD.


Subject(s)
COVID-19/drug therapy , Cardiovascular Diseases , Resveratrol , SARS-CoV-2/metabolism , Biological Availability , COVID-19/complications , COVID-19/metabolism , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Humans , Resveratrol/pharmacokinetics , Resveratrol/therapeutic use
16.
Cells ; 10(5)2021 05 04.
Article in English | MEDLINE | ID: covidwho-1223957

ABSTRACT

Liver injury in COVID-19 patients has progressively emerged, even in those without a history of liver disease, yet the mechanism of liver pathogenicity is still controversial. COVID-19 is frequently associated with increased serum ferritin levels, and hyperferritinemia was shown to correlate with illness severity. The liver is the major site for iron storage, and conditions of iron overload have been established to have a pathogenic role in development of liver diseases. We presented here six patients who developed severe COVID-19, with biochemical evidence of liver failure. Three cases were survived patients, who underwent liver biopsy; the other three were deceased patients, who were autopsied. None of the patients suffered underlying liver pathologies. Histopathological and ultrastructural analyses were performed. The most striking finding we demonstrated in all patients was iron accumulation into hepatocytes, associated with degenerative changes. Abundant ferritin particles were found enclosed in siderosomes, and large aggregates of hemosiderin were found, often in close contact with damaged mitochondria. Iron-caused oxidative stress may be responsible for mitochondria metabolic dysfunction. In agreement with this, association between mitochondria and lipid droplets was also found. Overall, our data suggest that hepatic iron overload could be the pathogenic trigger of liver injury associated to COVID-19.


Subject(s)
COVID-19/diagnosis , Iron Overload/etiology , Liver Failure/etiology , Liver/pathology , Severity of Illness Index , Adult , Aged , Antiviral Agents , Biopsy , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Female , Ferritins/analysis , Hepatocytes/cytology , Hepatocytes/pathology , Humans , Iron/analysis , Iron/metabolism , Iron Overload/mortality , Iron Overload/pathology , Iron Overload/therapy , Liver/cytology , Liver/metabolism , Liver Failure/mortality , Liver Failure/pathology , Liver Failure/therapy , Liver Function Tests , Male , Middle Aged , Mitochondria/pathology , Positive-Pressure Respiration , SARS-CoV-2/isolation & purification
17.
Antioxidants (Basel) ; 10(5)2021 May 09.
Article in English | MEDLINE | ID: covidwho-1223916

ABSTRACT

Recent reports have demonstrated the association between type 1 diabetes mellitus (T1DM) and increased morbidity and mortality rates during coronavirus disease (COVID-19) infection, setting a priority of these patients for vaccination. Impaired innate and adaptive immunity observed in T1DM seem to play a major role. Severe, life-threatening COVID-19 disease is characterized by the excessive release of pro-inflammatory cytokines, known as a "cytokine storm". Patients with T1DM present elevated levels of cytokines including interleukin-1a (IL), IL-1ß, IL-2, IL-6 and tumor necrosis factor alpha (TNF-α), suggesting the pre-existence of chronic inflammation, which, in turn, has been considered the major risk factor of adverse COVID-19 outcomes in many cohorts. Even more importantly, oxidative stress is a key player in COVID-19 pathogenesis and determines disease severity. It is well-known that extreme glucose excursions, the prominent feature of T1DM, are a potent mediator of oxidative stress through several pathways including the activation of protein kinase C (PKC) and the increased production of advanced glycation end products (AGEs). Additionally, chronic endothelial dysfunction and the hypercoagulant state observed in T1DM, in combination with the direct damage of endothelial cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may result in endothelial and microcirculation impairment, which contribute to the pathogenesis of acute respiratory syndrome and multi-organ failure. The binding of SARS-CoV-2 to angiotensin converting enzyme 2 (ACE2) receptors in pancreatic b-cells permits the direct destruction of b-cells, which contributes to the development of new-onset diabetes and the induction of diabetic ketoacidosis (DKA) in patients with T1DM. Large clinical studies are required to clarify the exact pathways through which T1DM results in worse COVID-19 outcomes.

18.
Intensive Care Med ; 47(5): 549-565, 2021 05.
Article in English | MEDLINE | ID: covidwho-1222758

ABSTRACT

PURPOSE: The trajectory of mechanically ventilated patients with coronavirus disease 2019 (COVID-19) is essential for clinical decisions, yet the focus so far has been on admission characteristics without consideration of the dynamic course of the disease in the context of applied therapeutic interventions. METHODS: We included adult patients undergoing invasive mechanical ventilation (IMV) within 48 h of intensive care unit (ICU) admission with complete clinical data until ICU death or discharge. We examined the importance of factors associated with disease progression over the first week, implementation and responsiveness to interventions used in acute respiratory distress syndrome (ARDS), and ICU outcome. We used machine learning (ML) and Explainable Artificial Intelligence (XAI) methods to characterise the evolution of clinical parameters and our ICU data visualisation tool is available as a web-based widget ( https://www.CovidUK.ICU ). RESULTS: Data for 633 adults with COVID-19 who underwent IMV between 01 March 2020 and 31 August 2020 were analysed. Overall mortality was 43.3% and highest with non-resolution of hypoxaemia [60.4% vs17.6%; P < 0.001; median PaO2/FiO2 on the day of death was 12.3(8.9-18.4) kPa] and non-response to proning (69.5% vs.31.1%; P < 0.001). Two ML models using weeklong data demonstrated an increased predictive accuracy for mortality compared to admission data (74.5% and 76.3% vs 60%, respectively). XAI models highlighted the increasing importance, over the first week, of PaO2/FiO2 in predicting mortality. Prone positioning improved oxygenation only in 45% of patients. A higher peak pressure (OR 1.42[1.06-1.91]; P < 0.05), raised respiratory component (OR 1.71[ 1.17-2.5]; P < 0.01) and cardiovascular component (OR 1.36 [1.04-1.75]; P < 0.05) of the sequential organ failure assessment (SOFA) score and raised lactate (OR 1.33 [0.99-1.79]; P = 0.057) immediately prior to application of prone positioning were associated with lack of oxygenation response. Prone positioning was not applied to 76% of patients with moderate hypoxemia and 45% of those with severe hypoxemia and patients who died without receiving proning interventions had more missed opportunities for prone intervention [7 (3-15.5) versus 2 (0-6); P < 0.001]. Despite the severity of gas exchange deficit, most patients received lung-protective ventilation with tidal volumes less than 8 mL/kg and plateau pressures less than 30cmH2O. This was despite systematic errors in measurement of height and derived ideal body weight. CONCLUSIONS: Refractory hypoxaemia remains a major association with mortality, yet evidence based ARDS interventions, in particular prone positioning, were not implemented and had delayed application with an associated reduced responsiveness. Real-time service evaluation techniques offer opportunities to assess the delivery of care and improve protocolised implementation of evidence-based ARDS interventions, which might be associated with improvements in survival.


Subject(s)
COVID-19 , Respiration, Artificial , Adult , Artificial Intelligence , Humans , Prone Position , SARS-CoV-2 , United Kingdom
19.
Lancet Diabetes Endocrinol ; 9(6): 350-359, 2021 06.
Article in English | MEDLINE | ID: covidwho-1208494

ABSTRACT

BACKGROUND: Obesity is a major risk factor for adverse outcomes after infection with SARS-CoV-2. We aimed to examine this association, including interactions with demographic and behavioural characteristics, type 2 diabetes, and other health conditions. METHODS: In this prospective, community-based, cohort study, we used de-identified patient-level data from the QResearch database of general practices in England, UK. We extracted data for patients aged 20 years and older who were registered at a practice eligible for inclusion in the QResearch database between Jan 24, 2020 (date of the first recorded infection in the UK) and April 30, 2020, and with available data on BMI. Data extracted included demographic, clinical, clinical values linked with Public Health England's database of positive SARS-CoV-2 test results, and death certificates from the Office of National Statistics. Outcomes, as a proxy measure of severe COVID-19, were admission to hospital, admission to an intensive care unit (ICU), and death due to COVID-19. We used Cox proportional hazard models to estimate the risk of severe COVID-19, sequentially adjusting for demographic characteristics, behavioural factors, and comorbidities. FINDINGS: Among 6 910 695 eligible individuals (mean BMI 26·78 kg/m2 [SD 5·59]), 13 503 (0·20%) were admitted to hospital, 1601 (0·02%) to an ICU, and 5479 (0·08%) died after a positive test for SARS-CoV-2. We found J-shaped associations between BMI and admission to hospital due to COVID-19 (adjusted hazard ratio [HR] per kg/m2 from the nadir at BMI of 23 kg/m2 of 1·05 [95% CI 1·05-1·05]) and death (1·04 [1·04-1·05]), and a linear association across the whole BMI range with ICU admission (1·10 [1·09-1·10]). We found a significant interaction between BMI and age and ethnicity, with higher HR per kg/m2 above BMI 23 kg/m2 for younger people (adjusted HR per kg/m2 above BMI 23 kg/m2 for hospital admission 1·09 [95% CI 1·08-1·10] in 20-39 years age group vs 80-100 years group 1·01 [1·00-1·02]) and Black people than White people (1·07 [1·06-1·08] vs 1·04 [1·04-1·05]). The risk of admission to hospital and ICU due to COVID-19 associated with unit increase in BMI was slightly lower in people with type 2 diabetes, hypertension, and cardiovascular disease than in those without these morbidities. INTERPRETATION: At a BMI of more than 23 kg/m2, we found a linear increase in risk of severe COVID-19 leading to admission to hospital and death, and a linear increase in admission to an ICU across the whole BMI range, which is not attributable to excess risks of related diseases. The relative risk due to increasing BMI is particularly notable people younger than 40 years and of Black ethnicity. FUNDING: NIHR Oxford Biomedical Research Centre.


Subject(s)
Body Mass Index , COVID-19/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Independent Living/trends , Severity of Illness Index , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , Cohort Studies , Databases, Factual , Diabetes Mellitus, Type 2/diagnosis , England/epidemiology , Female , Follow-Up Studies , Hospitalization/trends , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , Young Adult
20.
Front Cardiovasc Med ; 7: 588692, 2020.
Article in English | MEDLINE | ID: covidwho-1206264

ABSTRACT

Cardiovascular disease causes almost one third of deaths worldwide, and more than half are related to primary arterial hypertension (PAH). The occurrence of several deleterious events, such as hyperactivation of the renin-angiotensin system (RAS), and oxidative and inflammatory stress, contributes to the development of small vessel disease in PAH. Small resistance arteries are found at various points through the arterial tree, act as the major site of vascular resistance, and actively regulate local tissue perfusion. Experimental and clinical studies demonstrate that alterations in small resistance artery properties are important features of PAH pathophysiology. Diseased small vessels in PAH show decreased lumens, thicker walls, endothelial dysfunction, and oxidative stress and inflammation. These events may lead to altered blood flow supply to tissues and organs, and can increase the risk of thrombosis. Notably, PAH is prevalent among patients diagnosed with COVID-19, in whom evidence of small vessel disease leading to cardiovascular pathology is reported. The SARS-Cov2 virus, responsible for COVID-19, achieves cell entry through an S (spike) high-affinity protein binding to the catalytic domain of the angiotensin-converting enzyme 2 (ACE2), a negative regulator of the RAS pathway. Therefore, it is crucial to examine the relationship between small resistance artery disease, ACE2, and PAH, to understand COVID-19 morbidity and mortality. The scope of the present review is to briefly summarize available knowledge on the role of small resistance artery disease and ACE2 in PAH, and critically discuss their clinical relevance in the context of cardiovascular pathology associated to COVID-19.

SELECTION OF CITATIONS
SEARCH DETAIL