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1.
BMJ Open Diabetes Res Care ; 10(2)2022 04.
Article in English | MEDLINE | ID: covidwho-1779347

ABSTRACT

INTRODUCTION: This post hoc pooled analysis of four real-world studies (SURE Canada, Denmark/Sweden, Switzerland and UK) aimed to characterize the use of once-weekly (OW) semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: The Semaglutide Real-world Evidence (SURE) studies had a duration of ~30 weeks. Changes in glycated hemoglobin (HbA1c) and body weight (BW) were analyzed for the overall population and the following baseline subgroups: GLP-1RA-naïve/GLP-1RA switchers; body mass index <25/≥25-<30/≥30-<35/≥35 kg/m2; age <65/≥65 years; HbA1c <7%/≥7-≤8%/>8-≤9%/>9%; T2D duration <5/≥5-<10/≥10 years. Data for patients achieving treatment targets were analyzed in the overall population and the baseline HbA1c ≥7% subgroup. RESULTS: Of 1212 patients, 960 were GLP-1RA-naïve and 252 had switched to semaglutide from another GLP-1RA. In the overall population, HbA1c was reduced from baseline to end of study (EOS) by -1.1% point and BW by -4.7 kg; changes were significant for all subgroups. There were significantly larger reductions of HbA1c and BW in GLP-1RA-naïve versus GLP-1RA switchers and larger reductions in HbA1c for patients with higher versus lower baseline HbA1c. At EOS, 52.6% of patients in the overall population achieved HbA1c <7%. No new safety concerns were identified in any of the completed SURE studies. CONCLUSIONS: In this pooled analysis, patients with T2D initiating OW semaglutide showed significant improvements from baseline to EOS in HbA1c and BW across various baseline subgroups, including patients previously treated with a GLP-1RA other than semaglutide, supporting OW semaglutide use in clinical practice. TRAIL REGISTRATION NUMBERS: NCT03457012; NCT03631186; NCT03648281; NCT03876015.


Subject(s)
Diabetes Mellitus, Type 2 , Aged , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Glucagon-Like Peptides/therapeutic use , Glycated Hemoglobin A/analysis , Humans , Hypoglycemic Agents/therapeutic use
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317264

ABSTRACT

Objective: Hyperactivation of the immune system through obesity and diabetes may enhance infection severity complicated by Acute Respiratory Distress Syndrome (ARDS), the hallmark of severe COVID-19 disease. Objectives: to determine the circulatory biomarkers for macrophage activation at baseline and after serum glucose normalization in obese type 2 diabetes (OT2D) subjects. Methods: A case-controlled interventional pilot study in OT2D (n=23) and control subjects (n=23). Subjects underwent hyperinsulinemic clamp normalizing serum glucose. Plasma macrophage-related proteins were determined using Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement at baseline (control and OT2D subjects) and after 1-hour of insulin clamp (OT2D subjects only). Results: . Basal M1 macrophage activation was characterized by elevated levels of M1 macrophage-specific surface proteins, CD80 and CD38, and cytokines or chemokines (CXCL1, CXCL5, RANTES) released by activated M1 macrophages. Two potent M1 macrophage activation markers CXCL9 and CXCL10 were decreased in OT2D. Activated M2 macrophages were characterized by elevated levels of plasma CD163, TFGβ-1, MMP7 and MMP9 in OT2D. Conventional mediators of both M1 and M2 macrophage activation markers (IFN-γ, IL-4, IL-13) were not altered. No changes were observed in plasma levels of M1/M2 macrophage activation markers in OT2D in response to acute normalization of glycemia. Conclusion: In the basal state, macrophage activation markers are elevated, and these reflect the expression of circulatory cytokines, chemokines, growth factors and matrix metalloproteinases in obese individuals with type 2 diabetes, that were not changed by glucose normalisation. These differences may predispose the diabetic individuals to ARDS reflecting in increased COVID-19 disease severity.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315998

ABSTRACT

Introduction: Polycystic ovary syndrome (PCOS) women have a hypercoagulable state and are also at high risk for severe COVID-19 leading to thromboembolic complications and increased mortality;however, whether this is intrinsically due to PCOS or, alternatively, a consequence of its metabolic complications is unclear. Methods: : We determined plasma coagulation pathway protein levels in PCOS (n=146) and control (n=97) women recruited to a PCOS biobank. Circulating levels of a panel of 18 clotting pathway proteins were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. Results: : Cohorts were age matched, though PCOS had elevated body mass index (BMI)(p<0.001), insulin (p<0.001) and C-reactive protein (CRP)(p<0.0001). Eight pro-coagulation proteins were elevated in PCOS: plasminogen activator inhibitor-1 (PAI-1)(p<0.0001), fibrinogen (p<0.01), fibrinogen gamma chain (p<0.0001), fibronectin (p<0.01), von Willebrand factor (p<0.05), D-dimer (p<0.0001), P-selectin (p<0.05), and plasma kallikrein (p<0.001). However, two anticoagulant proteins, vitamin K-dependent protein-S (p<0.0001) and heparin cofactor-II (p<0.001) were elevated and prothrombin was decreased (p<0.05). CRP, as a marker of inflammation, and insulin resistance (HOMA-IR) correlated with 11 and 6 of the clotting proteins, respectively (p<0.05). When matched for BMI<25 (16 PCOS, 53 controls) HOMA-IR remained elevated (p<0.05) and heparin cofactor-II was increased (p<0.05). In a multivariate analysis accounting for inflammation, insulin resistance and BMI, there was no correlation of PCOS with any of the coagulation proteins. Conclusion: The hypercoagulable State in PCOS can be fully accounted for by BMI, inflammation and insulin resistance suggesting that only obese PCOS women would be predisposed to an enhanced risk for severe COVID-19-related disease.

4.
Life Sci ; 294: 120392, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1670857

ABSTRACT

The SARS coronavirus 2 (SARS CoV-2) causes Coronavirus Disease (COVID-19), is an emerging viral infection. SARS CoV-2 infects target cells by attaching to Angiotensin-Converting Enzyme (ACE2). SARS CoV-2 could cause cardiac damage in patients with severe COVID-19, as ACE2 is expressed in cardiac cells, including cardiomyocytes, pericytes, and fibroblasts, and coronavirus could directly infect these cells. Cardiovascular disorders are the most frequent comorbidity found in COVID-19 patients. Immune cells such as monocytes, macrophages, and T cells may produce inflammatory cytokines and chemokines that contribute to COVID-19 pathogenesis if their functions are uncontrolled. This causes a cytokine storm in COVID-19 patients, which has been associated with cardiac damage. Tregs are a subset of immune cells that regulate immune and inflammatory responses. Tregs suppress inflammation and improve cardiovascular function through a variety of mechanisms. This is an exciting research area to explore the cellular, molecular, and immunological mechanisms related to reducing risks of cardiovascular complications in severe COVID-19. This review evaluated whether Tregs can affect COVID-19-related cardiovascular complications, as well as the mechanisms through which Tregs act.


Subject(s)
COVID-19/immunology , Cardiovascular Diseases/immunology , Cardiovascular Diseases/prevention & control , SARS-CoV-2 , T-Lymphocytes, Regulatory/physiology , Adoptive Transfer , Animals , Cardiovascular Diseases/virology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/prevention & control , Humans , Inflammation/immunology , T-Lymphocytes, Regulatory/immunology
6.
Clin Endocrinol (Oxf) ; 96(4): 443-459, 2022 04.
Article in English | MEDLINE | ID: covidwho-1518007

ABSTRACT

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD). OBJECTIVE: To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS. DATA SOURCES: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021. STUDY SELECTION: The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). DATA EXTRACTION: Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection. DATA SYNTHESIS: In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I2 = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I2 = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I2 = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I2 = 75%, very low-grade evidence). CONCLUSION: There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.


Subject(s)
Metformin , Polycystic Ovary Syndrome , Atorvastatin/therapeutic use , C-Reactive Protein , Cholesterol, LDL , Female , Humans , Metformin/therapeutic use
7.
J Steroid Biochem Mol Biol ; 214: 105965, 2021 11.
Article in English | MEDLINE | ID: covidwho-1454329

ABSTRACT

Vitamin D deficiency is a negative endocrine renin-angiotensin system (RAS) modulator and PCOS women are often vitamin D deficient, leading to RAS overactivation in PCOS. A cross-sectional study was performed in 99 PCOS and 68 control women who presented sequentially. Circulating plasma levels of RAS proteins (Angiotensin-converting enzyme 2 (ACE2), renin and angiotensinogen) were measured by Slow Off-rate Modified Aptamer (SOMA)-scan and 25-hydroxyvitamin D [25(OH)D] was measured by tandem mass spectroscopy. The RAS system was found to be overactivated in the PCOS women compared to non-PCOS control women with increased renin and decreased angiotensinogen (p < 0.05); 25-hydroxyvitamin D was also significantly lower in the PCOS group (p < 0.0001). In PCOS women, plasma renin was increased in vitamin D deficient and insufficient groups compared with the vitamin D sufficient group (p < 0.005), but did not differ across non-PCOS control subgroups. In non-PCOS controls, plasma ACE2 decreased from vitamin D insufficiency to deficiency (p < 0.05). Angiotensinogen was not different across the vitamin D sufficiency, insufficiency and deficiency strata for either PCOS or non-PCOS controls. These data show that RAS activation through increased plasma renin levels was seen in vitamin D insufficient and deficient PCOS subjects compared to non-PCOS control women. In addition, decreased plasma ACE2 levels were seen in vitamin D deficiency in non-PCOS controls, which may predispose these vitamin D deficient subjects to increased cardiovascular risk and susceptibility to infectious agents such as COVID-19 where this is a risk factor.


Subject(s)
Angiotensin-Converting Enzyme 2/blood , Angiotensinogen/blood , Polycystic Ovary Syndrome/blood , Renin/blood , Vitamin D Deficiency/blood , Adult , Blood Pressure , Female , Humans , Polycystic Ovary Syndrome/physiopathology , Renin-Angiotensin System , Vitamin D/blood , Vitamin D Deficiency/physiopathology , Vitamins/blood , Young Adult
8.
Diabetes Ther ; 12(11): 2891-2905, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1437338

ABSTRACT

INTRODUCTION: Once-weekly (OW) semaglutide was associated with clinically relevant improvements in glycaemic control and body weight versus comparators in the SUSTAIN randomised controlled trials (RCTs). SURE UK, which is one of a series of individual studies that comprise the SURE programme, evaluated the use of OW semaglutide in a real-world patient population with type 2 diabetes (T2D) in the UK. METHODS: In this prospective, observational study, adults (≥ 18 years) with ≥ 1 documented glycated haemoglobin (HbA1c) value ≤ 12 weeks before semaglutide initiation were enrolled. The primary endpoint was change in HbA1c from baseline to end of study (EOS; ~ 30 weeks, although due to the COVID-19 pandemic, visits up to week 52 were permitted). Secondary endpoints included change in body weight, waist circumference and patient-reported outcomes (PROs). Physicians were to report all episodes of documented or severe hypoglycaemia, fatal events, serious adverse drug reactions, pregnancies and adverse events (AEs) in foetuses/newborn infants; other AEs during the study period could be reported on a voluntary basis. RESULT: The estimated mean change in HbA1c from baseline to EOS was - 16.3 mmol/mol [95% confidence interval (CI): - 18.22, - 14.37] (- 1.5%-points [95% CI - 1.67, - 1.31]; p < 0.0001) among the 171 enrolled patients who completed the study on treatment. Mean body weight change was - 5.8 kg (95% CI - 6.75, - 4.94; p < 0.0001). Sensitivity analyses showed similar results. Improvements were also observed in other secondary endpoints, including PROs. No new safety concerns were identified with semaglutide treatment. CONCLUSION: Patients receiving OW semaglutide experienced statistically significant and clinically relevant reductions from baseline in HbA1c and body weight. These results are in line with those of the SUSTAIN RCTs and support the use of OW semaglutide in routine clinical practice in adults with T2D in the UK. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03876015.

9.
Front Endocrinol (Lausanne) ; 12: 665134, 2021.
Article in English | MEDLINE | ID: covidwho-1305637

ABSTRACT

Introduction: Neuropilin-1(NRP1) is a cofactor that enhances SARS-CoV-2 coronavirus cell infectivity when co-expressed with angiotensin-converting enzyme 2(ACE2). The Renin-Angiotensin System (RAS) is activated in type 2 diabetes (T2D); therefore, the aim of this study was to determine if hypoglycaemia-induced stress in T2D would potentiate serum NRP1(sNRP1) levels, reflecting an increased risk for SARS-CoV-2 infection. Methods: A case-control study of aged-matched T2D (n = 23) and control (n = 23) subjects who underwent a hyperinsulinemic clamp over 1-hour to hypoglycemia(<40mg/dl) with subsequent timecourse of 4-hours and 24-hours. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement determined RAS-related proteins: renin (REN), angiotensinogen (AGT), ACE2, soluble NRP1(sNRP1), NRP1 ligands (Vascular endothelial growth factor, VEGF and Class 3 Semaphorins, SEM3A) and NRP1 proteolytic enzyme (A Disintegrin and Metalloproteinase 9, ADAM9). Results: Baseline RAS overactivity was present with REN elevated and AGT decreased in T2D (p<0.05); ACE2 was unchanged. Baseline sNRP1, VEGF and ADAM9 did not differ between T2D and controls and remained unchanged in response to hypoglycaemia. However, 4-hours post-hypoglycemia, sNRP1, VEGF and ADAM9 were elevated in T2D(p<0.05). SEMA3A was not different at baseline; at hypoglycemia, SEMA3A decreased in controls only. Post-hypoglycemia, SEMA3A levels were higher in T2D versus controls. sNRP1 did not correlate with ACE2, REN or AGT. T2D subjects stratified according to ACE inhibitor (ACEi) therapies showed no difference in sNRP1 levels at either glucose normalization or hypoglycaemia. Conclusion: Hypoglycemia potentiated both plasma sNRP1 level elevation and its ligands VEGF and SEMA3A, likely through an ADAM9-mediated mechanism that was not associated with RAS overactivity or ACEi therapy; however, whether this is protective or promotes increased risk for SARS-CoV-2 infection in T2D is unclear. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT03102801.


Subject(s)
ADAM Proteins/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Diabetes Mellitus, Type 2/metabolism , Hypoglycemia/metabolism , Membrane Proteins/metabolism , Neuropilin-1/metabolism , Semaphorin-3A/metabolism , Vascular Endothelial Growth Factor A/metabolism , Aged , Angiotensins/metabolism , COVID-19 , Female , Glucose Clamp Technique , Humans , Male , Middle Aged , Protective Factors , Renin/metabolism , Risk Factors , SARS-CoV-2
10.
Front Endocrinol (Lausanne) ; 12: 658304, 2021.
Article in English | MEDLINE | ID: covidwho-1305636

ABSTRACT

Objective: Detailed proteomic analysis in a cohort of patients with differing severity of COVID-19 disease identified biomarkers within the complement and coagulation cascades as biomarkers for disease severity has been reported; however, it is unclear if these proteins differ sufficiently from other conditions to be considered as biomarkers. Methods: A prospective, parallel study in T2D (n = 23) and controls (n = 23). A hyperinsulinemic clamp was performed and normoglycemia induced in T2D [4.5 ± 0.07 mmol/L (81 ± 1.2 mg/dl)] for 1-h, following which blood glucose was decreased to ≤2.0 mmol/L (36 mg/dl). Proteomic analysis for the complement and coagulation cascades were measured using Slow Off-rate Modified Aptamer (SOMA)-scan. Results: Thirty-four proteins were measured. At baseline, 4 of 18 were found to differ in T2D versus controls for platelet degranulation [Neutrophil-activating peptide-2 (p = 0.014), Thrombospondin-1 (p = 0.012), Platelet factor-4 (p = 0.007), and Kininogen-1 (p = 0.05)], whilst 3 of 16 proteins differed for complement and coagulation cascades [Coagulation factor IX (p < 0.05), Kininogen-1 (p = 0.05), and Heparin cofactor-2 (p = 0.007)]; STRING analysis demonstrated the close relationship of these proteins to one another. Induced euglycemia in T2D showed no protein changes versus baseline. At hypoglycemia, however, four proteins changed in controls from baseline [Thrombospondin-1 (p < 0.014), platelet factor-4 (p < 0.01), Platelet basic protein (p < 0.008), and Vitamin K-dependent protein-C (p < 0.00003)], and one protein changed in T2D [Vitamin K-dependent protein-C, (p < 0.0002)]. Conclusion: Seven of 34 proteins suggested to be biomarkers of COVID-19 severity within the platelet degranulation and complement and coagulation cascades differed in T2D versus controls, with further changes occurring at hypoglycemia, suggesting that validation of these biomarkers is critical. It is unclear if these protein changes in T2D may predict worse COVID-19 disease for these patients. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT03102801.


Subject(s)
Blood Coagulation Factors/metabolism , COVID-19/metabolism , Diabetes Mellitus, Type 2/metabolism , Hypoglycemia/metabolism , Aged , Biomarkers/metabolism , Blood Coagulation , Case-Control Studies , Complement Activation , Factor IX/metabolism , Female , Glucose Clamp Technique , Heparin Cofactor II/metabolism , Humans , Kininogens/metabolism , Male , Middle Aged , Peptides/metabolism , Platelet Activation , Platelet Factor 4/metabolism , Prospective Studies , Protein C/metabolism , Proteomics , SARS-CoV-2 , Severity of Illness Index , Thrombospondin 1/metabolism , beta-Thromboglobulin/metabolism
11.
Front Endocrinol (Lausanne) ; 12: 651009, 2021.
Article in English | MEDLINE | ID: covidwho-1190304

ABSTRACT

Introduction: Patients with severe COVID-19 infections have coagulation abnormalities indicative of a hypercoagulable state, with thromboembolic complications and increased mortality. Platelets are recognized as mediators of inflammation, releasing proinflammatory and prothrombotic factors, and are hyperactivated in COVID-19 infected patients. Activated platelets have also been reported in type 2 diabetes (T2D) patients, putting these patients at higher risk for thromboembolic complications of COVID-19 infection. Methods: A case-control study of T2D (n=33) and control subjects (n=30) who underwent a hyperinsulinemic clamp to induce normoglycemia in T2D subjects: T2D: baseline glucose 7.5 ± 0.3mmol/l (135.1 ± 5.4mg/dl), reduced to 4.5 ± 0.07mmol/l (81 ± 1.2mg/dl) with 1-hour clamp; Controls: maintained at 5.1 ± 0.1mmol/l (91.9 ± 1.8mg/dl). Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was used to determine a panel of platelet proteins. Results: Prothrombotic platelet proteins were elevated in T2D versus controls: platelet factor 4 (PF4, p<0.05); platelet glycoprotein VI (PGVI p<0.05); P-selectin (p<0.01) and plasminogen activator inhibitor I (PAI-1, p<0.01). In addition, the antithrombotic platelet-related proteins, plasmin (p<0.05) and heparin cofactor II (HCFII, p<0.05), were increased in T2D. Normalization of glucose in the T2D cohort had no effect on platelet protein levels. Conclusion: T2D patients have platelet hyperactivation, placing them at higher risk for thromboembolic events. When infected with COVID-19, this risk may be compounded, and their propensity for a more severe COVID-19 disease course increased. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03102801, identifier NCT03102801.


Subject(s)
Blood Platelet Disorders/blood , Blood Platelet Disorders/etiology , Blood Platelets/chemistry , Blood Proteins/analysis , COVID-19/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Hypoglycemia/blood , Hypoglycemia/complications , Aged , COVID-19/complications , Case-Control Studies , Female , Glucose Clamp Technique , Humans , Lipids/blood , Male , Middle Aged , Platelet Activation , Thromboembolism/blood , Thromboembolism/etiology
13.
Sci Rep ; 11(1): 6428, 2021 03 19.
Article in English | MEDLINE | ID: covidwho-1142462

ABSTRACT

Hyperactivation of the immune system through obesity and diabetes may enhance infection severity complicated by Acute Respiratory Distress Syndrome (ARDS). The objective was to determine the circulatory biomarkers for macrophage activation at baseline and after serum glucose normalization in obese type 2 diabetes (OT2D) subjects. A case-controlled interventional pilot study in OT2D (n = 23) and control subjects (n = 23). OT2D subjects underwent hyperinsulinemic clamp to normalize serum glucose. Plasma macrophage-related proteins were determined using Slow Off-rate Modified Aptamer-scan plasma protein measurement at baseline (control and OT2D subjects) and after 1-h of insulin clamp (OT2D subjects only). Basal M1 macrophage activation was characterized by elevated levels of M1 macrophage-specific surface proteins, CD80 and CD38, and cytokines or chemokines (CXCL1, CXCL5, RANTES) released by activated M1 macrophages. Two potent M1 macrophage activation markers, CXCL9 and CXCL10, were decreased in OT2D. Activated M2 macrophages were characterized by elevated levels of plasma CD163, TFGß-1, MMP7 and MMP9 in OT2D. Conventional mediators of both M1 and M2 macrophage activation markers (IFN-γ, IL-4, IL-13) were not altered. No changes were observed in plasma levels of M1/M2 macrophage activation markers in OT2D in response to acute normalization of glycemia. In the basal state, macrophage activation markers are elevated, and these reflect the expression of circulatory cytokines, chemokines, growth factors and matrix metalloproteinases in obese individuals with type 2 diabetes, that were not changed by glucose normalisation. These differences could potentially predispose diabetic individuals to increased infection severity complicated by ARDS. Clinical trial reg. no: NCT03102801; registration date April 6, 2017.


Subject(s)
COVID-19/etiology , Diabetes Mellitus, Type 2/complications , Macrophage Activation , Obesity/complications , Adult , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , Cytokines/blood , Cytokines/immunology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/immunology , Female , Humans , Inflammation/blood , Inflammation/complications , Inflammation/immunology , Male , Middle Aged , Obesity/blood , Obesity/immunology , Pilot Projects , Prospective Studies , Risk Factors
14.
J Pregnancy ; 2021: 8870129, 2021.
Article in English | MEDLINE | ID: covidwho-1138466

ABSTRACT

BACKGROUND: Based on what is known at this time, pregnant women are at an increased risk of severe illness from COVID-19 compared to nonpregnant women. Additionally, pregnant women with COVID-19 might have an increased risk of adverse pregnancy outcomes. To investigate the effects of coronavirus disease 2019 (COVID-19) on mortality of pregnant and postpartum women, we performed a systematic review of available published literature on pregnancies affected by COVID-19. METHODS: Web of Science, SCOPUS, and MEDLINE- databases were searched for original studies concerning the effect of COVID-19 on mortality of pregnant and postpartum women published by July 10, 2020. Meta-analyses of proportions were used to combine data and report pooled proportions. RESULTS: 117 studies with a total of 11758 pregnant women were included. The age ranged between 15 and 48 years. Most subjects were infected with SARS-CoV-2 in the third trimester. Disease severity was not reported in 1125 subjects. Maternal mortality was 1.3%. In 100% of fatal cases with adequate data, fever alone or with cough was one of the presenting symptoms. Also, dyspnea (58.3%) and myalgia (50%) were the most common symptoms. Sore throat (8.3%) and gastrointestinal symptoms (anorexia, nausea) (8.3%) were rare. The rate of comorbidities was 20% among COVID-19 deaths. The majority of COVID-19-infected women who died had cesarean section (58.3%), 25% had a vaginal delivery, and 16.7% of patients were not full term. CONCLUSION: COVID-19 infection in pregnant women was associated with higher rates (and pooled proportions) of cesarean section and mortality. Because new data are continuously being generated and published, the findings of this study can be complete and updated with new researches. The results of this study can guide and improve prenatal counseling of COVID-19-infected pregnant women.


Subject(s)
COVID-19/mortality , Pregnancy Complications, Infectious/mortality , Female , Global Health , Humans , Maternal Mortality , Models, Statistical , Postpartum Period , Pregnancy
16.
Front Endocrinol (Lausanne) ; 12: 638621, 2021.
Article in English | MEDLINE | ID: covidwho-1133905

ABSTRACT

Background: Women with polycystic ovary syndrome (PCOS) often have vitamin D deficiency, a known risk factor for severe COVID-19 disease. Alveolar macrophage-derived cytokines contribute to the inflammation underlying pulmonary disease in COVID-19. We sought to determine if basal macrophage activation, as a risk factor for COVID-19 infection, was present in PCOS and, if so, was further enhanced by vitamin D deficiency. Methods: A cross-sectional study in 99 PCOS and 68 control women who presented sequentially. Plasma levels of a macrophage-derived cytokine panel were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. Vitamin D was measured by tandem mass spectroscopy. Results: Vitamin D was lower in PCOS women (p<0.0001) and correlated negatively with body mass index (BMI) in PCOS (r=0.28, p=0.0046). Basal macrophage activation markers CXCL5, CD163 and MMP9 were elevated, whilst protective CD200 was decreased (p<0.05); changes in these variables were related to, and fully accounted for, by BMI. PCOS and control women were then stratified according to vitamin D concentration. Vitamin D deficiency was associated with decreased CD80 and IFN-γ in PCOS and IL-12 in both groups (p<0.05). These factors, important in initiating and maintaining the immune response, were again accounted for by BMI. Conclusion: Basal macrophage activation was higher in PCOS with macrophage changes related with increased infection risk associating with vitamin D; all changes were BMI dependent, suggesting that obese PCOS with vitamin D deficiency may be at greater risk of more severe COVID-19 infection, but that it is obesity-related rather than an independent PCOS factor.


Subject(s)
COVID-19/epidemiology , Cytokines/metabolism , Macrophages/metabolism , Polycystic Ovary Syndrome/epidemiology , Vitamin D Deficiency/epidemiology , Adult , Biomarkers/analysis , Blood Proteins/analysis , Body Mass Index , COVID-19/complications , COVID-19/immunology , Cross-Sectional Studies , Female , Humans , Macrophage Activation , Macrophages/chemistry , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/immunology , Risk Assessment , Tandem Mass Spectrometry , Vitamin D/blood , Vitamin D Deficiency/complications
17.
Adv Exp Med Biol ; 1321: 325-333, 2021.
Article in English | MEDLINE | ID: covidwho-1114260

ABSTRACT

Coronavirus 2019 (COVID-19) is responsible for the current pandemic which has already resulted in considerable mortality worldwide. This systematic review was conducted to summarize the results of the published articles assessing the incidence of heart diseases in patients infected with COVID-19. The electronic databases Scopus, Web of Science, Pubmed, Science Direct, and ProQuest were used to search for potentially relevant articles. Articles published from Dec 2019 to April 2020 were included. All cross-sectional, retrospective or prospective observational cohort and case-control studies were selected which reported the incidence or prevalence of myocardial injury, myocardial infarction, or cardiovascular disease in patients with confirmed COVID-19 infection. Based on the inclusion criteria, 12 articles were selected. The incidence of cardiac injury was reported in 8 articles and 8 articles focused on the cardiovascular outcomes of COVID-19 infection. The incidence of new cardiac injury was reported to be 7.2-77% in live and dead patients, respectively. The results showed that patients with cardiac injury had worse outcomes including higher mortality than those without cardiac injury. The most common cardiac injury outcomes were shock and malignant arrhythmias. The most common radiographic findings in patients with cardiac injury were multiple mottling and ground-glass opacities in the lungs (64.6%). A significant number of patients with cardiac injury required noninvasive mechanical ventilation (46.3%) or invasive mechanical ventilation (22.0%). Acute respiratory distress syndrome was seen in 58.5%, acute kidney injury in 8.5%, electrolyte disturbances in 15.9%, hypoproteinemia in 13.4%, and coagulation disorders in 7.3% of patients with cardiac injuries. In addition, survival days were negatively correlated with cardiac troponin I levels (r = -0.42, 95%, p = 0.005). The results of this review showed that myocardial injury in patients with COVID 19 has a poor prognosis. Hence, cardiac investigation and management in these patients are crucial.


Subject(s)
COVID-19 , Coronavirus , Cross-Sectional Studies , Humans , Retrospective Studies , SARS-CoV-2
18.
Adv Exp Med Biol ; 1321: 253-260, 2021.
Article in English | MEDLINE | ID: covidwho-1114253

ABSTRACT

Aim The ongoing COVID-19 outbreak has not only had an impact on physical health but also on psychological health. The aim of this study was to measure the prevalence and severity of psychological distress in the community due to the COVID-19 pandemic. Methods This cross-sectional survey was conducted in February and March 2020 in Tehran, Iran. We analyzed demographic characteristics and assessed depression, anxiety, and stress levels in 241 people using convenience sampling and the DASS-21 questionnaire. All statistical analyses were performed using R. Results The study population included 241 community-dwelling participants, of whom 145 were women and 96 were males. The mean age was 49.16 ± 8.01 years. Approximately two-thirds of participants (n = 158) reported no history of comorbid illness. The mean scores of depression and stress were at a "severe" level, while anxiety levels were at an "extremely severe" level. The prevalence of severe and extremely severe depression readings was 51.45 and 38.17%, respectively. In the anxiety subscale, the prevalence of severe and extremely severe depression was 95.90 and 4.1%, and in the stress subscale the prevalence was 48.97 and 4.98%, respectively. Conclusion In this study, people reported experiencing severe and extremely severe psychological distress. Therefore, there is an urgent need to implement mental health intervention policies to cope with this ongoing challenge. We suggest that the incorporation of molecular biomarker tests into the algorithm could aid in assessment of patients and guide the most appropriate therapeutic response.


Subject(s)
COVID-19 , Psychological Distress , Adult , Anxiety/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Female , Humans , Iran/epidemiology , Male , Middle Aged , Pandemics , SARS-CoV-2 , Stress, Psychological/epidemiology , Surveys and Questionnaires
19.
Adv Exp Med Biol ; 1321: 245-251, 2021.
Article in English | MEDLINE | ID: covidwho-1114252

ABSTRACT

Aim The COVID-19 was declared a pandemic in early 2020 and is associated with high public anxiety all over the world. The healthcare community is at the highest risk of infection and thereby prone to most distress. The aim of this study was to explore and evaluate the degree of depression, anxiety, and stress levels among medical college students during the COVID-19 epidemic in Iran. Methods A cross-sectional study was conducted in February and March 2020, 3 weeks after the first reported COVID-19 infection was identified in Iran. All medical college students who entered clinical courses were eligible for the study. Depression, stress, and anxiety were evaluated in these students using the DASS-21 questionnaire. Participants were selected by using availability sampling. All statistical analyses were performed using R version 3.5.1. Results The total number of participants was 207, with 143 males and 64 females. More than half of the participants (57.97%) were married. The mean duration of working experience among students with COVID-19 infection and experience in a medical ward was 3.00 ± 1.27 days and 17.40 ± 7.26 months, respectively. The majority of students had 2 or 3 days working experience with COVID-19 infection. The mean anxiety score of participants was 28.56 ± 4.68, the depression score was 29.36 ± 4.42, and the stress score was 28.99 ± 4.53. Our findings indicated that the mean scores of depression were at an "extremely severe" level, while stress and anxiety were at "severe" levels. The prevalence of "severe" symptoms of depression, stress, and anxiety was 69.57%, 60.87%, and 99.04%, respectively. Conclusions There is a high prevalence of anxiety and depression among medical students who were exposed to COVID-19-infected patients. Our results highlight the need to establish psychological support programs, training, and self-care for medical college students in relation to mental health. We recommend incorporation of molecular biomarker tests into an algorithm to aid in assessments and consideration of the appropriate therapeutic responses.


Subject(s)
COVID-19 , Coronavirus , Psychological Distress , Students, Medical , Anxiety/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Female , Humans , Iran/epidemiology , Male , SARS-CoV-2 , Stress, Psychological/epidemiology , Surveys and Questionnaires
20.
Adv Exp Med Biol ; 1321: 237-243, 2021.
Article in English | MEDLINE | ID: covidwho-1114251

ABSTRACT

AIM: The outbreak of COVID-19 has laid unprecedented psychological stress on healthcare workers (HCWs). We aimed to assess the immediate psychological impact of COVID-19 epidemic on the HCWs at Baqiyatallah Hospital in Tehran, Iran. MATERIAL AND METHODS: We conducted a cross-sectional survey of HCWs using questionnaires in February and March 2020 in Baqiyatallah Hospital, Tehran. We evaluated depression, stress, and anxiety levels using the DASS-21 questionnaire. Participants were selected by using census sampling. All statistical analyses were performed using R version 3.5.1. RESULTS: The study population included 217 HCWs (111 male, 116 female) and the mean age of the study group was 39.6 years old. Approximately two-thirds of the HCWs stayed in the hospital for 2-3 weeks. The mean scores of depression and stress were at a "severe" level, while anxiety scores were at an "extremely severe" level. The prevalence of severe scores was 38.71%, 2.30%, and 48.97% for depression, anxiety, and stress, and the prevalence of extremely severe scores was 46.54%, 97.24%, and 4.98% depression, anxiety, and stress, respectively. In stress subscale, moderate stress was 47.46%. Female HCWs reported higher levels of depression compared with males. CONCLUSION: In this study, HCWs reported experiencing severe and extremely severe psychological burdens. Timely interventions to promote mental health in HCWs exposed to patients with COVID-19 need to be immediately implemented, with female nurses requiring particular attention. This process could be facilitated via tests for molecular biomarkers in accessible body fluids, such as saliva, plasma, and serum.


Subject(s)
COVID-19 , Epidemics , Psychological Distress , Adult , Anxiety/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Female , Health Personnel , Humans , Iran/epidemiology , Male , SARS-CoV-2 , Stress, Psychological/epidemiology , Surveys and Questionnaires
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