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1.
Front Cardiovasc Med ; 7: 593061, 2020.
Article in English | MEDLINE | ID: covidwho-1485041

ABSTRACT

Since December 2019, coronavirus disease 2019 (COVID-19) caused by a novel coronavirus has spread all over the world affecting tens of millions of people. Another pandemic affecting the modern world, type 2 diabetes mellitus is among the major risk factors for mortality from COVID-19. Current evidence, while limited, suggests that proper blood glucose control may help prevent exacerbation of COVID-19 even in patients with type 2 diabetes mellitus. Under current circumstances where the magic bullet for the disease remains unavailable, it appears that the role of blood glucose control cannot be stressed too much. In this review the profile of each anti-diabetic agent is discussed in relation to COVID-19.

2.
Ghana Med J ; 54(4 Suppl): 52-61, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1436195

ABSTRACT

INTRODUCTION: Since the declaration of COVID-19 by the World Health Organisation (WHO) as a global pandemic on 11th March 2020, the number of deaths continue to increase worldwide. Reports on its pathologic manifestations have been published with very few from the Sub-Saharan African region. This article reports autopsies on COVID-19 patients from the Ga-East and the 37 Military Hospitals to provide pathological evidence for better understanding of COVID-19 in Ghana. METHODS: Under conditions required for carrying out autopsies on bodies infected with category three infectious agents, with few modifications, complete autopsies were performed on twenty patients with ante-mortem and/or postmortem RT -PCR confirmed positive COVID-19 results, between April and June, 2020. RESULTS: There were equal proportion of males and females. Thirteen (65%) of the patients were 55years or older with the same percentage (65%) having Type II diabetes and/or hypertension. The most significant pathological feature found at autopsy was diffuse alveolar damage. Seventy per cent (14/20) had associated thromboemboli in the lungs, kidneys and the heart. Forty per cent (6/15) of the patients that had negative results for COVID-19 by the nasopharyngeal swab test before death had positive results during postmortem using bronchopulmonary specimen. At autopsy all patients were identified to have pre-existing medical conditions. CONCLUSION: Diffuse alveolar damage was a key pathological feature of deaths caused by COVID-19 in all cases studied with hypertension and diabetes mellitus being major risk factors. Individuals without co-morbidities were less likely to die or suffer severe disease from SARS-CoV-2. FUNDING: None declared.


Subject(s)
Autopsy/statistics & numerical data , COVID-19/pathology , Hospitals, Military/statistics & numerical data , Hospitals, Municipal/statistics & numerical data , SARS-CoV-2 , COVID-19/mortality , COVID-19 Testing/methods , COVID-19 Testing/statistics & numerical data , Comorbidity , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/virology , Female , Ghana/epidemiology , Humans , Hypertension/mortality , Hypertension/virology , Lung/pathology , Lung/virology , Male , Middle Aged , Pulmonary Alveoli/pathology , Pulmonary Alveoli/virology , Risk Factors
3.
Tob Induc Dis ; 19: 09, 2021.
Article in English | MEDLINE | ID: covidwho-1404153

ABSTRACT

INTRODUCTION: COVID-19 has major effects on the clinical, humanistic and economic outcomes among patients, producing severe symptoms and death. Smoking has been reported as one of the factors that increases severity and mortality rate among COVID-19 patients. However, the effect of smoking on such medical outcomes is still controversial. This study conducted a comprehensive systematic review and meta-analysis (SR/MA) on the association between smoking and negative outcomes among COVID-19 patients. METHODS: Electronic databases, including PubMed, EMBASE, Cochrane Library, Science Direct, Google Scholar, were systematically searched from the initiation of the database until 12 December 2020. All relevant studies about smoking and COVID-19 were screened using a set of inclusion and exclusion criteria. The Newcastle-Ottawa Scale was used to assess the methodological quality of eligible articles. Random meta-analyses were conducted to estimate odds ratios (ORs) with 95% confidence interval (CIs). Publication bias was assessed using the funnel plot, Begg's test and Egger's test. RESULTS: A total of 1248 studies were retrieved and reviewed. A total of 40 studies were finally included for meta-analysis. Both current smoking and former smoking significantly increase the risk of disease severity (OR=1.58; 95% CI: 1.16-2.15, p=0.004; and OR=2.48; 95% CI: 1.64-3.77, p<0.001; respectively) with moderate appearance of heterogeneity. Similarly, current smoking and former smoking also significantly increase the risk of death (OR=1.35; 95% CI: 1.12-1.62, p=0.002; and OR=2.58; 95% CI: 2.15-3.09, p<0.001; respectively) with moderate appearance of heterogeneity. There was no evidence of publication bias, which was tested by the funnel plot, Begg's test and Egger's test. CONCLUSIONS: Smoking, even current smoking or former smoking, significantly increases the risk of COVID-19 severity and death. Further causational studies on this association and ascertianing the underlying mechanisms of this relation is warranted.

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.
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
6.
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
7.
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.

8.
World J Virol ; 10(3): 97-110, 2021 May 25.
Article in English | MEDLINE | ID: covidwho-1256932

ABSTRACT

The first cases of coronavirus disease 2019 (COVID-19) were detected in Wuhan, China, in December 2019. Since this time a concerted global effort of research and observational data gathering has meant that a great deal has been learnt about the impact of COVID-19 in patients with lymphoid malignancies. Approximately one-third of patients with lymphoid malignancies who acquire COVID-19 and have it severely enough to require hospital assessment will die from this infection. Major risk factors for a poor outcome are age and co-morbidities, but when these are taken into account lymphoma patients have a slightly greater than 2-fold increased risk compared to the general population. Notably, despite early concerns regarding the particular vulnerability of lymphoma patients due to the immunosuppressive effects of therapy, active treatment, including B-cell depleting agents such as rituximab, do not appear to be associated with an increased risk of a poorer outcome. Indeed, some treatments such as ibrutinib may be beneficial due to their modulation of the potential fatal hyperinflammatory phase of infection. There are risks associated with hemopoietic stem cell transplantation, but the collective experience is that these can be minimized by preventive strategies and that the majority of transplant recipients with COVID-19 infection will survive. Many questions remain including those regarding the outcome of COVID-19 infection in the rarer lymphoid malignancies and the efficacy of COVID-19 vaccines in lymphoma patients. This review aims to discuss these issues and present a summary of the current knowledge of the impact of COVID-19 in lymphoid malignancies.

9.
BMJ Open ; 11(5): e050084, 2021 05 19.
Article in English | MEDLINE | ID: covidwho-1236465

ABSTRACT

OBJECTIVE: The outbreak of COVID-19 has major impacts on the psychological health of the public. This study aimed to investigate the anxiety and depression levels of the general population during the rapid progressing stage of COVID-19 pandemic in China and to explore the associated factors. DESIGN AND SETTING: A cross-sectional online survey. PARTICIPANTS: 2651 Chinese people. MEASURES: The Hospital Anxiety and Depression Scale was used to measure their psychological health. A structured questionnaire collected possible associated factors, including sociodemographic characteristics, health information, contact history-related information, experience and perceptions, knowledge and education and adopted precautions. Multiple linear regression was conducted to explore the factors associated with anxiety and depression. RESULTS: The mean score of anxiety and depression was 4.35 and 4.38, respectively. The rates of people with anxiety and depressive symptoms (with >7 score in the subscale) were 14.15% and 17.35%, respectively. Participants without political party membership, with contact history of COVID-19, going out or gathering, taking Chinese medicine herbs, being unsatisfied with current precautions, perceiving higher risks of infection, lower knowledge and poorer health presented higher anxiety and depression levels. Moreover, those who were females, married, lived alone and wore mask were more anxious; whereas people who were younger, experienced public health crisis, did not take precautions (regular work-rest, exercise) had higher depression level. CONCLUSIONS: During the rapid progressing stage of COVID-19 pandemic in China, one-seventh and one-sixth respondents presented anxiety and depression symptoms, respectively. The risk factors for anxiety and depression included the following: without political party membership, with contact history of COVID-19, going out or gathering, wearing masks, taking Chinese medicine herbs, being unsatisfied with current precautions, perceiving higher susceptibility, lower knowledge and poorer health status. Extensive information and psychological support should be provided to improve the mental health of the general population.


Subject(s)
COVID-19 , Pandemics , Anxiety/epidemiology , China/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Disease Outbreaks , Female , Humans , Male , SARS-CoV-2 , Surveys and Questionnaires
10.
Clin Infect Dis ; 72(10): e639-e641, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1232186

ABSTRACT

Choral singing has become a major risk during the coronavirus disease 2019 (COVID-19) pandemic due to high infection rates. Our visualization and velocimetry results reveal that the majority of droplets expelled during singing follow the ambient airflow pattern. These results point toward the possibility of COVID-19 spread by small airborne droplets during singing.


Subject(s)
COVID-19 , Singing , Aerosols , Humans , Pandemics , SARS-CoV-2
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.
Life Sci ; 278: 119580, 2021 Aug 01.
Article in English | MEDLINE | ID: covidwho-1225325

ABSTRACT

COVID-19 pandemic is still a major risk to human civilization. Besides the global immunization policy, more than five lac new cases are documented everyday. Some countries newly implement partial/complete nationwid lockdown to mitigate recurrent community spreading. To avoid the new modified stain of SARS-CoV-2 spreading, some countries imposed any restriction on the movement of the citizens within or outside the country. Effective economical point of care diagnostic and therapeutic strategy is vigorously required to mitigate viral spread. Besides struggling with repurposed medicines, new engineered materials with multiple unique efficacies and specific antiviral potency against SARS-CoV-2 infection may be fruitful to save more lives. Nanotechnology-based engineering strategy sophisticated medicine with specific, effective and nonhazardous delivery mechanism for available repurposed antivirals as well as remedial for associated diseases due to malfeasance in immuno-system e.g. hypercytokinaemia, acute respiratory distress syndrome. This review will talk about gloomy but critical areas for nanoscientists to intervene and will showcase about the different laboratory diagnostic, prognostic strategies and their mode of actions. In addition, we speak about SARS-CoV-2 pathophysiology, pathogenicity and host specific interation with special emphasis on altered immuno-system and also perceptualized, copious ways to design prophylactic nanomedicines and next-generation vaccines based on recent findings.


Subject(s)
COVID-19/therapy , Theranostic Nanomedicine/methods , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/immunology , COVID-19/pathology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/therapeutic use , Drug Delivery Systems/methods , Humans , Immunization/methods , Nanotechnology/methods , Precision Medicine/methods , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
13.
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
14.
Cells ; 10(4)2021 04 17.
Article in English | MEDLINE | ID: covidwho-1194614

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.


Subject(s)
COVID-19/complications , Obesity/complications , Animals , COVID-19/immunology , COVID-19/pathology , Chronic Disease , Humans , Immunity , Inflammation/complications , Inflammation/immunology , Inflammation/pathology , Insulin Resistance , 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
15.
New Microbes New Infect ; 41: 100864, 2021 May.
Article in English | MEDLINE | ID: covidwho-1174438

ABSTRACT

The elderly form the main risk group in the coronavirus disease 2019 (COVID-19) pandemic, and age is recognized as a major risk factor for the severity of infection and mortality of COVID-19. The severity of the infection in children is milder than in adults. Although the pathophysiology of COVID-19 is not fully understood, several possible factors and mechanisms have been suggested for the lower severity of infection in children.

16.
J Chem Inf Model ; 61(4): 2062-2073, 2021 04 26.
Article in English | MEDLINE | ID: covidwho-1157886

ABSTRACT

During almost all 2020, coronavirus disease 2019 (COVID-19) pandemic has constituted the major risk for the worldwide health and economy, propelling unprecedented efforts to discover drugs for its prevention and cure. At the end of the year, these efforts have culminated with the approval of vaccines by the American Food and Drug Administration (FDA) and the European Medicines Agency (EMA) giving new hope for the future. On the other hand, clinical data underscore the urgent need for effective drugs to treat COVID-19 patients. In this work, we embarked on a virtual screening campaign against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Mpro chymotrypsin-like cysteine protease employing our in-house database of peptide and non-peptide ligands characterized by different types of warheads acting as Michael acceptors. To this end, we employed the AutoDock4 docking software customized to predict the formation of a covalent adduct with the target protein. In vitro verification of the inhibition properties of the most promising candidates allowed us to identify two new lead inhibitors that will deserve further optimization. From the computational point of view, this work demonstrates the predictive power of AutoDock4 and suggests its application for the in silico screening of large chemical libraries of potential covalent binders against the SARS-CoV-2 Mpro enzyme.


Subject(s)
COVID-19 , Protease Inhibitors , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , Pandemics , Protease Inhibitors/pharmacology , SARS-CoV-2
17.
J Appl Physiol (1985) ; 130(5): 1470-1478, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1150256

ABSTRACT

Survivors from COVID-19 pneumonia can present with persisting multisystem involvement (lung, pulmonary vessels, heart, muscle, red blood cells) that may negatively affect exercise capacity. We sought to determine the extent and the determinants of exercise limitation in patients with COVID-19 at the time of hospital discharge. Eighteen consecutive patients with COVID-19 and 1:1 age-, sex-, and body mass index-matched controls underwent: spirometry, echocardiography, cardiopulmonary exercise test and exercise echocardiography for the study of pulmonary circulation. Arterial blood was sampled at rest and during exercise in patients with COVID-19. Patients with COVID-19 lie roughly on the same oxygen consumption isophlets than controls both at rest and during submaximal exercise, thanks to supernormal cardiac output (P < 0.05). Oxygen consumption at peak exercise was reduced by 30% in COVID-19 (P < 0.001), due to a peripheral extraction limit. In addition, within COVID-19 patients, hemoglobin content was associated with peak oxygen consumption (R2 = 0.46, P = 0.002). Respiratory reserve was not exhausted (median [IRQ], 0.59 [0.15]) in spite of moderate reduction of forced vital capacity (79 ± 40%). Pulmonary artery pressure increase during exercise was not different between patients and controls. Ventilatory equivalents for carbon dioxide were higher in patients with COVID-19 than in controls (39.5 [8.5] vs. 29.5 [8.8], P < 0.001), and such an increase was mainly explained by increased chemosensitivity. When recovering from COVID-19, patients present with reduced exercise capacity and augmented exercise hyperventilation. Peripheral factors, including anemia and reduced oxygen extraction by peripheral muscles were the major determinants of deranged exercise physiology. Pulmonary vascular function seemed unaffected, despite restrictive lung changes.NEW & NOTEWORTHY At the time of hospital discharge, patients with COVID-19 present with reduced functional capacity and exercise hyperventilation. Peripheral factors, namely reduced oxygen extraction (myopathy) and anemia, which are not fully compensated by a supernormal cardiac output response, account for exercise limitation before exhaustion of the respiratory reserve. Enhanced chemoreflex sensitivity, rather increased dead space, mainly accounts for exercise hyperventilation. The pulmonary vascular response to exercise circulation of survived patients with COVID-19 does not present major pathological changes.


Subject(s)
COVID-19 , Echocardiography , Exercise Test , Exercise Tolerance , Humans , Oxygen Consumption , SARS-CoV-2
18.
Risk Manag Healthc Policy ; 14: 1065-1072, 2021.
Article in English | MEDLINE | ID: covidwho-1140604

ABSTRACT

PURPOSE: This study aims to evaluate the overall emotional wellbeing and emotional predictors of the Saudi population during COVID-19. PATIENTS AND METHODS: A cross-sectional design was employed; the data were collected by using the Arabic version of the Mental Health Inventory. RESULTS: A total of 5041 participants were successfully recruited over 1 week. The participants scored moderately on Anxiety, Depression, Loss of Behavioral/Emotional Control, General Positive Affect, Emotional Ties, and Life Satisfaction. The results indicated that age, gender, marital status, socioeconomic status, and having chronic health conditions are major predictors of emotional wellbeing during the COVID-19 pandemic. CONCLUSION: A rehabilitation program should be initiated to restore the community function and the wellbeing of individuals who have been impacted by the COVID-19 pandemic.

19.
EBioMedicine ; 65: 103277, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1131243

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease, characterized by progressive lung scarring. Severe COVID-19 is associated with substantial pneumonitis and has a number of shared major risk factors with IPF. This study aimed to determine the genetic correlation between IPF and severe COVID-19 and assess a potential causal role of genetically increased risk of IPF on COVID-19 severity. METHODS: The genetic correlation between IPF and COVID-19 severity was estimated with linkage disequilibrium (LD) score regression. We performed a Mendelian randomization (MR) study for IPF causality in COVID-19. Genetic variants associated with IPF susceptibility (P<5 × 10-8) in previous genome-wide association studies (GWAS) were used as instrumental variables (IVs). Effect estimates of those IVs on COVID-19 severity were gathered from the GWAS meta-analysis by the COVID-19 Host Genetics Initiative (4,336 cases & 623,902 controls). FINDINGS: We detected a positive genetic correlation of IPF with COVID-19 severity (rg=0·31 [95% CI 0·04-0·57], P = 0·023). The MR estimates for severe COVID-19 did not reveal any genetic association (OR 1·05, [95% CI 0·92-1·20], P = 0·43). However, outlier analysis revealed that the IPF risk allele rs35705950 at MUC5B had a different effect compared with the other variants. When rs35705950 was excluded, MR results provided evidence that genetically increased risk of IPF has a causal effect on COVID-19 severity (OR 1·21, [95% CI 1·06-1·38], P = 4·24 × 10-3). Furthermore, the IPF risk-allele at MUC5B showed an apparent protective effect against COVID-19 hospitalization only in older adults (OR 0·86, [95% CI 0·73-1·00], P = 2·99 × 10-2) . INTERPRETATION: The strongest genetic determinant of IPF, rs35705950 at MUC5B, seems to confer protection against COVID-19, whereas the combined effect of all other IPF risk loci seem to confer risk of COVID-19 severity. The observed effect of rs35705950 could either be due to protective effects of mucin over-production on the airways or a consequence of selection bias due to (1) a patient group that is heavily enriched for the rs35705950 T undertaking strict self-isolation and/or (2) due to survival bias of the rs35705950 non-IPF risk allele carriers. Due to the diverse impact of IPF causal variants on SARS-CoV-2 infection, with a possible selection bias as an explanation, further investigation is needed to address this apparent paradox between variance at MUC5B and other IPF genetic risk factors. FUNDING: Novo Nordisk Foundation and Oak Foundation.


Subject(s)
COVID-19/pathology , Genetic Predisposition to Disease/genetics , Idiopathic Pulmonary Fibrosis/pathology , COVID-19/genetics , Genome-Wide Association Study , Humans , Idiopathic Pulmonary Fibrosis/genetics , Lung/pathology , Mucin-5B/genetics , Polymorphism, Single Nucleotide/genetics , Risk , SARS-CoV-2 , Severity of Illness Index
20.
Brain Behav Immun ; 94: 51-59, 2021 05.
Article in English | MEDLINE | ID: covidwho-1121360

ABSTRACT

In the face of the global coronavirus disease 2019 (COVID-19) pandemic, billions of people were forced to stay at home due to the implementation of social distancing and lockdown policies. As a result, individuals lost their social relationships, leading to social isolation and loneliness. Both social isolation and loneliness are major risk factors for poor physical and mental health status through enhanced chronic inflammation; however, there might be an interplay between social isolation and loneliness on the association with chronic inflammation. We aimed to clarify the link between social relationships and inflammation in the context of the COVID-19 pandemic by distinguishing whether social isolation only, loneliness only, or both were associated with chronic inflammation markers among community-dwelling adults. The data of 624 people (aged 18-92 years, mean 51.4) from the Utsunomiya COVID-19 seROprevalence Neighborhood Association (U-CORONA) study, which targeted randomly sampled households in Utsunomiya city, Japan, were analyzed. Social isolation was assessed as a structural social network by asking the number of social roles they have on a daily basis. Loneliness was measured with the UCLA loneliness scale. As chronic inflammation biomarkers, neutrophil-to-lymphocyte ratio (NLR) and the concentration of high-sensitivity C-reactive protein (CRP) were measured. Generalized estimating equations method was employed to take into account the correlations within households. Isolated-Lonely condition (i.e., being both socially isolated and feeling lonely) was associated with higher NLR among men (B = 0.141, 95%CI = -0.01 to 0.29). Interestingly, Nonisolated-Lonely condition (i.e., not socially isolated but feeling lonely) was associated with lower CRP among women (B = -0.462, 95%CI = -0.82 to -0.10) and among the working-age population (B = -0.495, 95%CI = -0.76 to -0.23). In conclusion, being both socially isolated and feeling lonely was associated with chronic inflammation. Assessing both social isolation and loneliness is critical for proper interventions to mitigate the impact of poor social relationships on health, especially in the context of the COVID-19 pandemic.


Subject(s)
COVID-19 , Pandemics , Adolescent , Adult , Aged , Aged, 80 and over , Communicable Disease Control , Female , Humans , Inflammation , Japan/epidemiology , Loneliness , Male , Middle Aged , SARS-CoV-2 , Seroepidemiologic Studies , Social Isolation , Young Adult
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