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This study aims to study the clinical-laboratory peculiarities of the coronavirus disease (COVID-19) course in patients with type 2 diabetes mellitus (DM). There were examined 60 patients with the coronavirus disease COVID-19. Patients were divided into two groups: group I - 30 patients with the coronavirus disease (COVID-19) with concomitant type 2 diabetes mellitus;group II - 30 patients with coronavirus disease (COVID-19) without diabetes mellitus;control group - 20 people. There were studied peculiarities of clinical-laboratory changes in patients with coronavirus disease with type 2 diabetes mellitus. General clinical laboratory tests, determination of biochemical parameters, coagulogram, ferritin, CRP, procalcitonin, D-dimer and endothelin-1 were performed. Blood saturation was measured. Out of the instrumental methods, an ultrasound examination of the lungs and RTG of thoracic organs was performed. Patients were admitted on the 5.46+/-0.87 day of the disease. The length of the hospital stay for patients of group I was 19.9+/-1.66 bed days and 14.7+/-0.91 bed days for the patients of group II. A severe course of the disease was observed in 83.3% of patients of group I and 33.3% of group II;a moderate severity course was observed in 16.7% of patients with concomitant DM and 66.7% of patients without concomitant DM. Respiratory failure (RF) of 1 degree was observed in 30% of patients of group 1, RF of the 2 degree - in 16.7% of patients, and RF of the 3 degree - in 10% of patients. In patients without DM, RF of 1 degree - was in 30% of patients, and RF of the 2 degree - was in 13.3% of patients. The laboratory diagnostic methods determined that the levels of leukocytes, D-dimer, endothelin-1, IL-6, procalcitonin, and ferritin were higher in patients with concomitant type 2 DM. In patients with type 2 DM, the course of the coronavirus disease is more severe and longer, with the development of pneumonia and respiratory failure. It is accompanied by leukocytosis, lymphopenia, increased ESR, prothrombin index, IL-6, CRP level, procalcitonin and endothelin-1. Copyright © 2023 The Authors.
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Introduction: COVID-19 is not only a respiratory disease, produces a severe systemic and multi-organ response. This illness generates vascular disorders, leading the patient to endothelial dysfunction. It acutely and chronically affects the patient's evolution, prolonging the patient's stay and worsening life prognosis. Objective(s): To evaluate differences in endothelial dysfunction present in patients hospitalized for COVID-19 who had a hospital stay longer than 18 days compared to those who did not. Method(s): A prospective cohort study was conducted. Hospitalized patients with confirmed SARS-COV 2 andolder than 18 years were included. Subjects in whom endothelial function markers could not be processed wereexcluded. Endothelial dysfunction was evaluated using E-selectin, endothelin-1, glutathione-s-transferase, arginase, and MDAM. A prolonged hospital stay was established >=18 days. Result(s): A total of 165 patients were evaluated, the average age of the population was 57.18 +/- 13.37 years, 73.33% were men. Subjects with prolonged hospital stay were older (59.38 +/- 12.08 vs 51.15 +/- 14.96, p=0.004), a higher number of patients required intubation (87.60 % vs 75, p=0.049) and e-selectin (1 [0.79 - 1.32] vs 0.88 [0.68 -1.14], p=0.0323) compared to subjects without prolonged hospital stay. Conclusion(s): Hospitalized patients over 18 days showed elevated levels of E-selectin reflecting endothelial damage, affecting vascular homeostasis, added to this, a significant number of them were intubated, increasing the risk of mortality, as well as future cardiovascular complications.
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Purpose. To establish the features of laboratory indicators of inflammation and endothelial dysfunction in persons with new SARS-CoV-2 coronavirus infection and pulmonary artery thromboembolism verified by computed tomographic angiography. Materials and methods. The study enrolled 116 patients with the confirmed coronavirus infection SARS-CoV-2 who were treated in the health care institution "4th City Clinical Hospital named after N.E. Savchenko" of Minsk in whom computed tomographic angiography (CTA) was performed to verify the diagnosis of pulmonary embolism (PE). The median age of the subjects was 62.0 (52.0–70.0) years, the proportion of males was 45.7% (53), females – 54.3% (63). The study group consisted of patients with SARS-COV-2 and confirmed diagnosis of PE (n=37), comparison group included patients with SARS-COV-2 whose diagnosis of PE was excluded on CTA (n=79). The formed groups were comparable by gender, age, presence of diabetes mellitus, bad habits, degree of arterial hypertension, and severity of course of COVID-19. The serum levels of tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), big endothelin-1 (Big ET-1), homocysteine were determined on the day when CTA was performed by enzyme immunoassay (EIA). A level of D-dimer on the day when CTA was performed was additionally analyzed. Results. In individuals with coronavirus infection and PE group mean values of IL-6, D-dimer, big ET-1, and homocysteine were significantly higher compared with the group without PE: 41.65 (21.84–136.36) versus 25.79 (15.93–36.17) pg/mL (U=135, p<0.05);2058.5 (826.0–4026.0) versus 982.5 (656.5–1936.0) ng/mL (U=141.5, p<0.05);0.34 (0.26– 0.51) versus 0.29 (0.07–0.38) pg/ml (U=137, p<0.05);19.55 (13.81–23.84) versus 16.01 (11.07–19.13) pg/ml (U=139, p<0.05) respectively. There were no significant differences between group mean values of TNF-a, interleukin-1β in the study and comparison groups. In the group of patients with PE and COVID-19 values of IL-6 and big ET-1 (ρ=0.66;p<0.05);TNF-a (ρ=0.62;p<0.05) were moderately positively correlated, values of IL-6 and D-dimer (ρ=0.78;p<0.05);interleukin-1β (ρ=0.80;p<0.05) were highly positively correlated. Conclusion. The obtained data demonstrates that in patients with COVID-19 and PE the course of the disease is accompanied by a more pronounced increase in serum levels of markers of inflammation (IL-6) and endothelial dysfunction (large endothelin-1, homocysteine). The correlation between the levels of IL-6 and big ET-1, D-dimer indicates the association of the activity of systemic inflammation with the level of endothelial dysfunction markers. © 2022, Professionalnye Izdaniya. All rights reserved.
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Background The translatability of the dual-endothelin1/VEGFsp receptor (DEspR) in human was first described in 2016 and its functionality is largely unknown since DEspR is not expressed in healthy human tissues except for kidney tissue and certain tumors. Recently, DEspR expression was reported on human neutrophil subsets of acute respiratory distress syndrome (ARDS) and COVID19-ADRS patients. DEspR+ neutrophil levels correlated with disease severity and mortality which may root in their delayed apoptosis and facilitated formation of neutrophil extracellular traps. Neutrophils play a major role in inflammation of chronic respiratory diseases and altered levels of DEspR ligands ET-1 and VEGF are found in COPD and asthma phenotypes. Here, we investigated the DEspR expression on human leukocyte populations of asthmatics, COPD patients and healthy smokers as well as on the human promyelocytic leucaemic cell line HL-60. Methods DEspR expression was measured on undifferentiated, promyelocytic HL-60 cells and after differentiation towards a neutrophilic phenotype using 1.25% DMSO. Expression was also measured after stimulation with 50 μg/mL poly I:C or 100 ng/mL LPS. Whole blood cells of COPD patients (step III, IV), healthy smokers and asthmatics (step III) were stained directly after blood draw or after stimulation with 50 μg/mL poly I:C or 100 ng/mL LPS. HL-60 and whole blood leukocytes were stained with Annexin V, 7AAD, DEspR (rhIgG4, clone 6g8), CD11b, CD14 and CD16a. Results Undifferentiated CD11b-, CD14- CD16a- and differentiated CD11b+, CD14-, CD16a- HL-60 cells did not express DEspR, neither with or without inflammatory stimulation. DespR was not expressed on whole blood leukocytes at baseline level (mean±SD: 0.15±0.26 to 0.91±0.60%) but poly I:C induced DEspR expression on neutrophils (34.10±18.52%), monocytes (29.16±20.00%), lymphocytes (9.67±6.11%) and eosinophils (6.14±4.39%). The distribution of DEspR+ cells upon poly I:C stimulation was not significantly altered among different disease types, however, healthy smokers showed a trend to higher DEspR levels. The median fluorescence intensity was not significantly altered among disease types but among the cell populations. Conclusion First experiments demonstrated that DEspR expression can be induced on leukocytes upon inflammatory stimulation. In contrast to previous results of us, LPS did not induce DEspR expression which might be related to differences in the age and disease severity of investigated patients. Interestingly, poly I:C induced a strong DEspR expression indicating a toll-like receptor 3 related mechanism. The sample size needs to be increased to confirm these first results and to investigate the underlying mechanism in detail.
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The aim. To analyze the blood levels of endothelin-1 (ET - 1) and high molecular weight kininogen (HMWK) in patients with breast cancer (BC) previously infected with the new coronavirus. Material and methods. The study group included 20 patients with stage II - IV BC (invasive carcinoma). All patients were receiving chemotherapy at the time of their SA RS-CoV-2 infection. The comparison group included 19 women without breast cancer, who were matched for age. All women of both groups had an RT-PC R confirmed SA RS-Cov-2 infection. Blood levels of ET - 1 and HMWK were measured by ELISA 3-10 weeks after the positive antigen test results. The control group included 10 women of the same age without cancer and without CO VID - 19 symptoms and anti-SA RS-CoV-2 antibodies. Results. The ET - 1 levels in the comparison group were within the reference range, while HMWK levels were significantly higher than those in breast cancer patients. In BC patients with lung metastases, the ET - 1 levels were higher than those in the comparison group patients, while in others (no history of lung metastases, with mild infection course or pneumonia), the ET - 1 levels were similar to those in the comparison and control groups. The HMWK levels in the study and comparison groups were significantly higher than those in controls. Among BC patients, there were women who had significantly higher ET - 1 and HMWK levels compared to the reference levels, and the majority of these patients had lung metastases and previous CO VID - 19 pneumonia. Conclusion. The measurement of HMWK blood levels demonstrated that the plasma contact activation system and the kallikrein-kinin system were active for a long period after the infection both in BC patients and in women without cancer. A high level of ET - 1, the endothelial dysfunction marker, persisted for a long time in some BC patients. Our results were consistent with results of other studies supporting the hypothesis that SA RS-CoV-2 virus infection is a systemic vascular disease with long-term consequences, and its mechanisms require further study.
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BACKGROUND: Fatigue, exertion intolerance and post-exertional malaise are among the most frequent symptoms of Post-COVID Syndrome (PCS), with a subset of patients fulfilling criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). As SARS-CoV-2 infects endothelial cells, causing endotheliitis and damaging the endothelium, we investigated endothelial dysfunction (ED) and endothelial biomarkers in patients with PCS. METHODS: We studied the endothelial function in 30 PCS patients with persistent fatigue and exertion intolerance as well as in 15 age- and sex matched seronegative healthy controls (HCs). 14 patients fulfilled the diagnostic criteria for ME/CFS. The other patients were considered to have PCS. Peripheral endothelial function was assessed by the reactive hyperaemia index (RHI) using peripheral arterial tonometry (PAT) in patients and HCs. In a larger cohort of patients and HCs, including post-COVID reconvalescents (PCHCs), Endothelin-1 (ET-1), Angiopoietin-2 (Ang-2), Endocan (ESM-1), IL-8, Angiotensin-Converting Enzyme (ACE) and ACE2 were analysed as endothelial biomarkers. RESULTS: Five of the 14 post-COVID ME/CFS patients and five of the 16 PCS patients showed ED defined by a diminished RHI (< 1.67), but none of HCs exhibited this finding. A paradoxical positive correlation of RHI with age, blood pressure and BMI was found in PCS but not ME/CFS patients. The ET-1 concentration was significantly elevated in both ME/CFS and PCS patients compared to HCs and PCHCs. The serum Ang-2 concentration was lower in both PCS patients and PCHCs compared to HCs. CONCLUSION: A subset of PCS patients display evidence for ED shown by a diminished RHI and altered endothelial biomarkers. Different associations of the RHI with clinical parameters as well as varying biomarker profiles may suggest distinct pathomechanisms among patient subgroups.
Subject(s)
COVID-19 , Fatigue Syndrome, Chronic , Biomarkers , COVID-19/complications , Endothelial Cells , Endothelium , Humans , SARS-CoV-2 , Post-Acute COVID-19 SyndromeABSTRACT
Virus induced endothelial dysregulation is a well-recognised feature of severe Covid-19 infection. Endothelin-1 (ET-1) is the most highly expressed peptide in endothelial cells and a potent vasoconstrictor, thus representing a potential therapeutic target. ET-1 plasma levels were measured in a cohort of 194 Covid-19 patients stratified according to the clinical severity of their illness. Hospitalised patients, including those who died and those developing acute myocardial or kidney injury, had significantly elevated ET-1 plasma levels during the acute phase of infection. The results support the hypothesis that endothelin receptor antagonists may provide clinical benefit for certain Covid-19 patients.
Subject(s)
COVID-19 , Endothelin-1 , Endothelial Cells , Endothelin Receptor Antagonists , Humans , Receptor, Endothelin A , Receptors, Endothelin , Vasoconstrictor AgentsABSTRACT
An increasing interest in a healthy lifestyle raises questions about optimal body weight. Evidently, it should be clearly discriminated between the standardised "normal" body weight and individually optimal weight. To this end, the basic principle of personalised medicine "one size does not fit all" has to be applied. Contextually, "normal" but e.g. borderline body mass index might be optimal for one person but apparently suboptimal for another one strongly depending on the individual genetic predisposition, geographic origin, cultural and nutritional habits and relevant lifestyle parameters-all included into comprehensive individual patient profile. Even if only slightly deviant, both overweight and underweight are acknowledged risk factors for a shifted metabolism which, if being not optimised, may strongly contribute to the development and progression of severe pathologies. Development of innovative screening programmes is essential to promote population health by application of health risks assessment, individualised patient profiling and multi-parametric analysis, further used for cost-effective targeted prevention and treatments tailored to the person. The following healthcare areas are considered to be potentially strongly benefiting from the above proposed measures: suboptimal health conditions, sports medicine, stress overload and associated complications, planned pregnancies, periodontal health and dentistry, sleep medicine, eye health and disorders, inflammatory disorders, healing and pain management, metabolic disorders, cardiovascular disease, cancers, psychiatric and neurologic disorders, stroke of known and unknown aetiology, improved individual and population outcomes under pandemic conditions such as COVID-19. In a long-term way, a significantly improved healthcare economy is one of benefits of the proposed paradigm shift from reactive to Predictive, Preventive and Personalised Medicine (PPPM/3PM). A tight collaboration between all stakeholders including scientific community, healthcare givers, patient organisations, policy-makers and educators is essential for the smooth implementation of 3PM concepts in daily practice.
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Background: Endothelial damage caused by COVID-19 may imperil the cardiovascular health of millions. More than a year since WHO declared the COVID-19 pandemic, information on the lasting effects of this infection on the cardiovascular system beyond the acute phase is still lacking. Purpose: To study macrovascular endothelial dysfunction and activation, coagulation and inflammation, 3 months after resolution of acute COVID- 19 symptoms. Methods: A cross-sectional observational cohort study was conducted including 203 patients with PCR confirmed COVID-19 disease, 6-20 weeks after acute COVID-19. The primary endpoint was macrovascular endothelial function, assessed by the carotid artery reactivity (CAR) test. The CAR measures the carotid artery diameter in response to hand in icewater immersion. A historic cohort of 313 subjects served as controls. Propensity score matching was used to correct for baseline differences. Plasma endothelin-1 (ET-1), interleukin (IL)-1ra, IL-6, IL-18 were measured by ELISA. ET-1 levels were also measured in a partially overlapping COVID-19 cohort of which plasma samples were available during the acute phase. Coagulation enzyme:inhibitor complexes for thrombin:antithrombin (TAT), factor (F) IXa:AT, FVIIa:AT, FXIa:AT, FXIa:alpha 1 antitrypsin (a1AT), FXIa:C1 esterase inhibitor (C1inh), kallikrein(PKa):C1inh and von Willebrand Factor:antigen (vWF:Ag), were assessed by in house developed ELISA. Results: After propensity score matching, the prevalence of macrovascular dysfunction did not differ between the COVID-19 (22.5%) versus the historical control cohort (18.6%, RD -3.92%, 95%-CI -15 to 7.19, p=0.49). Plasma concentrations of markers for endothelial activation were elevated (>1 SD above normal);ET-1 (64.9%), and vWF:Ag (80.8%). In controls, ET- 1 levels were significantly lower as compared to COVID-19 patients during the acute phase and after 3 months. ET-1 levels were significantly higher 3 months after COVID-19 as compared to the acute phase. Cytokines were high in a majority of patients: IL-18 (73.9%), IL-6 (51.2%), and IL- 1ra (48.9%). TAT and FIXa:AT, reflecting a prothrombotic state, were high in 48.3% and 29.6% of the patients, respectively. FVIIa:AT, as marker of the extrinsic pathway, was elevated (35%). Markers of contact activation were also increased: PKa:C1inh (16.3%), FXIa:AT (16.3%), FXIa:a1AT (20.7%), and FXIa:C1inh (17.7%) (picture 1). Conclusions: At 3 months after acute COVID-19 there was no indication of macrovascular dysfunction as compared to matched historic controls;there was evidence, however, of sustained thrombo-inflammation, indicated by high circulating concentrations of ET-1, vWF:Ag, proinflammatory cytokines, and markers of coagulation (picture 2). Elevated IL-18 levels could potentially induce arterial inflammation and subsequent atherogenesis. Our data highlight the importance of further studies on SARS-CoV-2 related thrombo-inflammation, as well as longer follow-ups in recovered patients. (Figure Presented).
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BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been linked to thrombotic complications and endothelial dysfunction. We assessed the prognostic implications of endothelial activation through measurement of endothelin-I precursor peptide (proET-1), the stable precursor protein of Endothelin-1, in a well-defined cohort of patients hospitalized with COVID-19. METHODS: We measured proET-1 in 74 consecutively admitted adult patients with confirmed COVID-19 and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and viral bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality. RESULTS: Overall, median admission proET-1 levels were lower in COVID-19 patients compared to those with pneumonia and exacerbated bronchitis, respectively (57.0 pmol/l vs. 113.0 pmol/l vs. 96.0 pmol/l, p < 0.01). Although COVID-19 non-survivors had 1.5-fold higher admission proET-1 levels compared to survivors (81.8 pmol/l [IQR: 76 to 118] vs. 53.6 [IQR: 37 to 69]), no significant association of proET-1 levels and mortality was found in a regression model adjusted for age, gender, creatinine level, diastolic blood pressure as well as cancer and coronary artery disease (adjusted OR 0.1, 95% CI 0.0009 to 14.7). In patients with pneumonia (adjusted OR 25.4, 95% CI 5.1 to 127.4) and exacerbated bronchitis (adjusted OR 120.1, 95% CI 1.9 to 7499) we found significant associations of proET-1 and mortality. CONCLUSIONS: Compared to other types of pulmonary infection, COVID-19 shows only a mild activation of the endothelium as assessed through measurement of proET-1. Therefore, the high mortality associated with COVID-19 may not be attributed to endothelial dysfunction by the surrogate marker proET-1.
Subject(s)
COVID-19/mortality , COVID-19/physiopathology , Endothelin-1/analysis , Endothelium, Vascular/physiopathology , Protein Precursors/analysis , Age Factors , Aged , Aged, 80 and over , Biomarkers/analysis , Blood Pressure , Cohort Studies , Creatinine/blood , Endpoint Determination , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Reproducibility of Results , Risk Factors , Sex Factors , Survival AnalysisABSTRACT
COVID-19 is an ongoing viral pandemic disease that is caused by SARS-CoV2, inducing severe pneumonia in humans. However, several classes of repurposed drugs have been recommended, no specific vaccines or effective therapeutic interventions for COVID-19 are developed till now. Viral dependence on ACE-2, as entry receptors, drove the researchers into RAS impact on COVID-19 pathogenesis. Several evidences have pointed at Neprilysin (NEP) as one of pulmonary RAS components. Considering the protective effect of NEP against pulmonary inflammatory reactions and fibrosis, it is suggested to direct the future efforts towards its potential role in COVID-19 pathophysiology. Thus, the review aimed to shed light on the potential beneficial effects of NEP pathways as a novel target for COVID-19 therapy by summarizing its possible molecular mechanisms. Additional experimental and clinical studies explaining more the relationships between NEP and COVID-19 will greatly benefit in designing the future treatment approaches.