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IMPORTANCE: Since the beginning of the COVID-19 pandemic, numerous metabolic alterations have been observed in individuals with this disease. It is known that SARS-CoV-2 can mimic the action of hepcidin, altering intracellular iron metabolism, but gaps remain in the understanding of possible outcomes in other pathways involved in the iron cycle. OBJECTIVE: To profile iron, ferritin and hepcidin levels and transferrin receptor gene expression in patients diagnosed with COVID-19 between June 2020 and September 2020. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study that evaluated iron metabolism markers in 427 participants, 218 with COVID-19 and 209 without the disease. EXPOSURES: The primary exposure was positive diagnose to COVID-19 in general population of Santo André and São Bernardo cities. The positive and negative diagnose were determinate through RT-qPCR. MAIN OUTCOMES AND MEASURES: Devido a evidências de alterações do ciclo do ferro em pacientes diagnosticados com COVID-19 e devido a corregulação entre hepcidina e receptor de transferrina, uma análise da expressão gênica deste último, poderia trazer insights sobre o estado de ferro celular. A hipótese foi confirmada, mostrando aumento da expressão de receptor de transferrina concomitante com redução do nível de hepcidina circulante. RESULTS: Serum iron presented lower values in individuals diagnosed with COVID-19, whereas serum ferritin presented much higher values in infected patients. Elderly subjects had lower serum iron levels and higher ferritin levels, and men with COVID-19 had higher ferritin values than women. Serum hepcidin was lower in the COVID-19 patient group and transferrin receptor gene expression was higher in the infected patient group compared to controls. CONCLUSIONS AND RELEVANCE: COVID-19 causes changes in several iron cycle pathways, with iron and ferritin levels being markers that reflect the state and evolution of infection, as well as the prognosis of the disease. The increased expression of the transferrin receptor gene suggests increased iron internalization and the mimicry of hepcidin action by SARS-CoV-2, reduces iron export via ferroportin, which would explain the low circulating levels of iron by intracellular trapping.
Subject(s)
COVID-19 , Transferrin , Male , Humans , Female , Aged , Transferrin/analysis , Hepcidins , Cross-Sectional Studies , Pandemics , SARS-CoV-2 , Iron/metabolism , Ferritins , Receptors, Transferrin , HomeostasisABSTRACT
Objective: Acute-phase proteins are a family of proteins synthesized by the liver. With this study, we aimed to investigate the effects of COVID-19 infection on acute phase reactants (AFR) and determine the usability of AFRs as prognostic factors in COVID-19 disease. Material(s) and Method(s): Serum samples taken for routine analysis of the patients admitted to the Emergency Department and diagnosed with COVID-19, were used. AFR levels of 30 patients who resulted in mortality and 30 recovered patients were evaluated. C-reactive protein (CRP), ferritin (FER), ceruloplasmin (Cp), albumin (Alb), prealbumin (Prealb), transferrin (Trf), lactate, Acute Physiology and Chronic Health Evaluation (APACHE), and Sequential Organ Failure Assessment (SOFA) assessment was performed. Result(s): The hazard ratio and 95% confidence interval for FER, CRP, lactate, Alb, Cp, Prealb, Trf, Age, SOFA, and APACHE were 1.001 (1.000-1.001), 1.005 (1.001- 1.008), 1.141 (1.016-1.243), 1.016 (0.740-1.399), 1.016 (0.740-1.399), 1.056 (1.017-1.100), 0.978 (0.917-1.035), 1.000 (0.995-1.006), 1.032 (1.004- 1.064), 1.104 (0.971-1.247), and 1.012 (0.974-1.051), respectively, in univariable model. Only CRP, lactate, and FER found significant in multivariable model. In addition, patients in the nonsurvivors group had significantly higher FER, CRP, lactate, APACHE, age, and SOFA. Nonsurvivors also had lower Alb, Prealb, and serum Trf level compared to survivors. Conclusion(s): CRP, lactate, and FER, which we have shown to be significantly higher in severe COVID-19 patients, will be valuable parameters that will contribute to clinical improvement if they are used in the follow-up of patients due to their easy measurement and predictive values.Copyright © 2023, Nobelmedicus. All rights reserved.
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The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves dysregulations of iron metabolism, and although the mechanism of this pathology is not yet fully understood, correction of iron metabolism pathways seems a promising pharmacological target. The previously observed effect of inhibiting SARS-CoV-2 infection by ferristatin II, an inducer of transferrin receptor 1 (TfR1) degradation, prompted the study of competition between Spike protein and TfR1 ligands, especially lactoferrin (Lf) and transferrin (Tf). We hypothesized molecular mimicry of Spike protein as cross-reactivity of Spike-specific antibodies with Tf and Lf. Thus, strong positive correlations (R2 > 0.95) were found between the level of Spike-specific IgG antibodies present in serum samples of COVID-19-recovered and Sputnik V-vaccinated individuals and their Tf-binding activity assayed with peroxidase-labeled anti-Tf. In addition, we observed cross-reactivity of Lf-specific murine monoclonal antibody (mAb) towards the SARS-CoV-2 Spike protein. On the other hand, the interaction of mAbs produced to the receptor-binding domain (RBD) of the Spike protein with recombinant RBD protein was disrupted by Tf, Lf, soluble TfR1, anti-TfR1 aptamer, as well as by peptides RGD and GHAIYPRH. Furthermore, direct interaction of RBD protein with Lf, but not Tf, was observed, with affinity of binding estimated by KD to be 23 nM and 16 nM for apo-Lf and holo-Lf, respectively. Treatment of Vero E6 cells with apo-Lf and holo-Lf (1-4 mg/mL) significantly inhibited SARS-CoV-2 replication of both Wuhan and Delta lineages. Protective effects of Lf on different arms of SARS-CoV-2-induced pathogenesis and possible consequences of cross-reactivity of Spike-specific antibodies are discussed.
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Introduction: This study aims to assess the association of inflammatory markers with the clinical progression of patients diagnosed with COVID-19. Material(s) and Method(s): Critically ill patients with COVID-19 were included. Prealbumin, lactate dehydrogenase (LDH), transferrin, procalcitonin, ferritin, D-dimer, troponin T and C-reactive protein (CRP) were monitored. A comparison was performed between patients regarding their need for mechanical ventilation, duration of hospital and intensive care unit stay, discharge, mortality, complications, and response to treatment in order to reveal potential correlations. Result(s): A total of 107 patients were enrolled in the study. D-dimer levels on the 3rd and 6th days were significantly higher in the exitus group. Prealbumin and transferrin levels measured at baseline and on days three and six were significantly lower in the exitus group compared to the surviving group (p< 0.05). In the exitus group, the procalcitonin, CRP, LDH, troponin T, and ferritin levels were significantly higher on days zero, three, and six as compared to the surviving group (p< 0.05). Conclusion(s): Our results suggest that inflammatory markers may be useful as early indicators of mortality in COVID-19 patients.Copyright © 2023 Bilimsel Tip Yayinevi. All rights reserved.
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Numerous blood biomarkers are altered in COVID-19 patients;however, no early biochemical markers are currently being used in clinical practice to predict COVID-19 severity. COVID-19, the most recent pandemic, is caused by the SRS-CoV-2 coronavirus. The study was aimed to identify patient groups with a high and low risk of developing COVID-19 using a cluster analysis of several biomarkers. 137 women with confirmed SARS CoV-2 RNA testing were collected and analyzed for biochemical profiles. Two-dimensional automated hierarchy clustering of all biomarkers was applied, and patients were sorted into classes. Biochemistry marker variations (Ferritin, lactate dehydrogenase LDH, D-dimer, and C- reactive protein CRP) have split COVID-19 patients into two groups(severe cases and non-severe cases groups). Ferritin, lactate dehydrogenase LDH, D-dimer and CRP were markedly increased in COVID-19 patients in the first group (severe cases). Our findings imply that early measured levels of (Ferritin, lactate dehydrogenase LDH, D-dimer, and C- reactive protein CRP) are linked to a decreased probability of COVID-19 severity. Elevated levels of this biomarker may predict COVID severity development.
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Introduction: Protein energy wasting (PEW) is an established entity in adults with CKD but is not well studied in children. The burden of PEW has been observed to be higher in Indian children with CKD compared to the chronic kidney disease in children (CKiD) cohort. The impact of PEW on outcomes needs to be addressed in these children with CKD. This prospective longitudinal study was undertaken in children with CKD 2-5D to assess the association of PEW with clinical outcomes of infection related hospital admissions (IRHA). Method(s): Children (age 2-18 years) with CKD 2-5D, from a tertiary care center were recruited for PEW assessment from January 2017 following ethical committee approval and informed consent. Children with evidence of infection in the last month and those on dialysis for less than a month were excluded. Demographic characteristics and clinical outcomes of hospital admissions were recorded till June 2022. Based on the CKiD study, PEW was diagnosed and categorized using 5 criteria: 1. Muscle mass (Mid arm muscle circumference);2. Body mass (body mass index);3. Biochemical parameters (serum cholesterol, serum albumin, serum transferrin, and C-reactive protein);4: Appetite and 5. Short stature. PEW was further categorized as mild (> 2 criteria), standard (> 3 criteria), and modified (> 3 criteria with short stature). Infections that needed hospitalization included viral hemorrhagic fever, COVID-19 infection, sepsis, urinary tract infection, lower respiratory tract infection, peritonitis, and catheter-related blood stream infection. Result(s): Among 136 children (45 on dialysis, mean age 122 + 46 months, 70% males) 72 (53%) had PEW. The proportions of those with mild, standard, and modified PEW were 8%, 13%, and 32% respectively. Over a mean follow-up of 38 + 21 months, 104 (76%) children required hospital admissions of which 69% were due to infections. Death was noted in 2%, and 12% got transplanted. The proportion of children needing hospital admissions was significantly higher in those with PEW compared to those without PEW (85% vs 66% respectively, p=0.011). IRHA was observed in 68% of children with PEW compared to 36% without PEW (p<0.001). The proportion of IRHA in those with dialysis with or without PEW ((87% vs 50%, p=0.001) was significantly higher compared to those with CKD 2-5 (54% vs 32%, p= 0.03). In the overall cohort, the proportion of IRHA was significantly higher with modified PEW compared to other PEW categories (p<0.001), [modified: 74.4%, standard: 58.0%, mild: 59%, no PEW: 36%]. On multivariable analysis, by adjusting for age, gender, etiology of CKD, and dialysis, the presence of PEW and dialysis status were independent factors associated with IRHA [Adjusted OR 3.58 (1.62,7.89), p=0.002] and [OR 3.29 (1.4,7.75), p=0.006, respectively]. Similarly, the presence of inflammation was independently associated with IRHA [OR 3.93 (1.49, 10.3), p=0.002]. Figure 1 shows the risk factors associated with IRHA based on PEW categories and inflammation status. [Formula presented] Conclusion(s): In children with CKD 2-5D, the presence of PEW and inflammation were significantly associated with IRHA. Children with modified PEW had nearly 5 times more risk of developing IRHA, reinforcing the importance of growth as a unique parameter of PEW in these children. No conflict of interestCopyright © 2023
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Aim: to build, a predictive model for severe COVID-19 prediction in young adults using deep learning methods. Material(s) and Method(s): data from 906 medical records of patients aged. 18 to 44 years with laboratory-confirmed SARS- CoV-2 infection during 2020-2021 period, was analyzed. Evaluation of laboratory and. instrumental data was carried out using the Mann-Whitney U-test. The level of statistical significance was p<0,05. The neural network was trained, using the Pytorch. framework. Result(s): in patients with mild to moderate SARS-CoV-2 infection, peripheral oxygen saturation, erythrocytes, hemoglobin, total protein, albumin, hematocrit, serum, iron, transferrin, and. absolute peripheral blood, eosinophil and. lymphocyte counts were significantly higher than in patients with severe SOVID-19 (p< 0,001). The values of the absolute number of neutrophils, ESR, glucose, ALT, AST, CPK, urea, LDH, ferritin, CRP, fibrinogen, D-dimer, respiration rate, heart rate, blood, pressure in the group of patients with mild and. moderate severity were statistically significantly lower than in the group of severe patients (p < 0.001). Eleven indicators were identified as predictors of severe COVID-19 (peripheral oxygen level, peripheral blood erythrocyte count, hemoglobin level, absolute eosinophil count, absolute lymphocyte count, absolute neutrophil count, LDH, ferritin, C-reactive protein, D-dimer levels) and. their threshold, values. A model intended, to predict COVID-19 severity in young adults was built. Conclusion. The values of laboratory and instrumental indicators obtained in patients with SARS-CoV-2 infection upon admission significantly differ. Among them, eleven indicators were significantly associated with the development of a severe COVID-19. A predictive model based, on artificial intelligence method, with high, accuracy predicts the likelihood, of severe SARS-CoV-2 course development in young adults.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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Aim: to build, a predictive model for severe COVID-19 prediction in young adults using deep learning methods. Material(s) and Method(s): data from 906 medical records of patients aged. 18 to 44 years with laboratory-confirmed SARS- CoV-2 infection during 2020-2021 period, was analyzed. Evaluation of laboratory and. instrumental data was carried out using the Mann-Whitney U-test. The level of statistical significance was p<0,05. The neural network was trained, using the Pytorch. framework. Result(s): in patients with mild to moderate SARS-CoV-2 infection, peripheral oxygen saturation, erythrocytes, hemoglobin, total protein, albumin, hematocrit, serum, iron, transferrin, and. absolute peripheral blood, eosinophil and. lymphocyte counts were significantly higher than in patients with severe SOVID-19 (p< 0,001). The values of the absolute number of neutrophils, ESR, glucose, ALT, AST, CPK, urea, LDH, ferritin, CRP, fibrinogen, D-dimer, respiration rate, heart rate, blood, pressure in the group of patients with mild and. moderate severity were statistically significantly lower than in the group of severe patients (p < 0.001). Eleven indicators were identified as predictors of severe COVID-19 (peripheral oxygen level, peripheral blood erythrocyte count, hemoglobin level, absolute eosinophil count, absolute lymphocyte count, absolute neutrophil count, LDH, ferritin, C-reactive protein, D-dimer levels) and. their threshold, values. A model intended, to predict COVID-19 severity in young adults was built. Conclusion. The values of laboratory and instrumental indicators obtained in patients with SARS-CoV-2 infection upon admission significantly differ. Among them, eleven indicators were significantly associated with the development of a severe COVID-19. A predictive model based, on artificial intelligence method, with high, accuracy predicts the likelihood, of severe SARS-CoV-2 course development in young adults.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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Iron is a mineral that plays an important role, especially to prevent anaemia through the production of red blood cells. Iron also plays a role in physiological processes, such as the activation of enzymes and hormones, as well as increasing the immune system in warding off various viral infections. Therefore, iron bioavailability needs to be considered to take the greatest benefit of iron. This review discussed the factors that can affect the bioavailability of iron, various technologies to increase the bioavailability, and its potential in enhancing the immune system. Iron bioavailability can be increased by fortification, fermentation, the addition of vitamin C, and iron encapsulation. Under conditions of adequate iron intake, iron plays an important role in enhancing the immune system through controlling lymphocytes and T cell proliferation. However, excess iron consumption can be at risk of weakening the host's immune response to viruses. Therefore, the appropriate level of iron intake must be maintained accurately to be used optimally and has the potential to ward off viral infections, including the Sars-CoV-2 virus as the cause of COVID-19.Copyright © 2023, Rynnye Lyan Resources. All rights reserved.
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Most colonoscopies performed to evaluate gastrointestinal symptoms detect only non-relevant pathologies. We aimed to evaluate the diagnostic accuracy of a qualitative point-of-care (POC) test combining four biomarkers (haemoglobin, transferrin, calprotectin, and lactoferrin), a quantitative faecal immunochemical test (FIT) for haemoglobin, and a quantitative faecal calprotectin (FC) test in symptomatic patients prospectively recruited. Colorectal cancer (CRC), adenoma requiring surveillance, inflammatory bowel disease (IBD), microscopic colitis, and angiodysplasia were considered significant pathologies. A total of 571 patients were included. Significant pathology was diagnosed in 118 (20.7%), including 30 CRC cases (5.3%). The POC test yielded the highest negative predictive values: 94.8% for a significant pathology and 100% for CRC or IBD if the four markers turned negative (36.8% of the patients). Negative predictive values of FIT, FC, and its combination for diagnosis of a significant pathology were 88.4%, 87.6%, and 90.8%, respectively. Moreover, the positive predictive value using the POC test was 82.3% for significant pathology when all biomarkers tested positive (6% of the patients), with 70.6% of these patients diagnosed with CRC or IBD. The AUC of the POC test was 0.801 (95%CI 0.754-0.848) for the diagnosis of a significant pathology. Therefore, this POC faecal test allows the avoidance of unnecessary colonoscopies and prioritizes high risk symptomatic patients.
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SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Mucormycosis is an angio-invasive fungal infection with substantial morbidity and mortality. While diabetes and immune suppression remain well-known risk factors for mucormycosis, COVID-19 is now emerging as its independent predictor. CASE PRESENTATION: A 43-year-old male, with a history of hyperlipidemia and alcoholism, presented to the hospital with complaints of progressive dyspnea on exertion, productive cough, intermittent fever, anorexia, and chest pain over the course of 2 weeks. About 5 weeks prior to the current presentation, he was tested positive for COVID-19 by a polymerase chain reaction (PCR) based test and remained in quarantine at home. He was not vaccinated against COVID-19. He had no known immunosuppressive disease. On initial examination, he was ill-appearing and had a temperature of 101 F, blood pressure 138/83 mmHg, respiratory rate 22/minute, pulse 102/minute, and saturation of 91% on 2 L nasal cannula oxygen. A computerized tomography (CT) scan of the chest revealed small bilateral pneumothorax (2 cm and 5mm) along with extensive ground-glass opacifications in all lobes. In the next 24 hours, the right-sided pneumothorax progressed to tension pneumothorax requiring pigtail pleural drainage catheter placement. The drained pleural fluid had more than 100,000/uL total nucleated cells (91% neutrophils, 2% lymphocytes, and 1% eosinophils) and ultimately cultures grew Rhizopus spp. He was started on intravenous liposomal amphotericin-B infusion (5 mg/kg daily). On hospital discharge, he was switched to oral posaconazole (started with loading 300 mg delayed-release tablet twice a day, followed by 300 mg dosing of delayed-release posaconazole tablets daily) to complete the long term treatment course. DISCUSSION: Most of the reported cases of mucormycosis in COVID-19 were in patients with either diabetes or receiving steroids. This is a rare presentation of COVID-19–associated pulmonary mucormycosis (CAPM) as spontaneous pneumothorax, in the absence of known immunosuppression history. COVID-19 results in a considerable increase in cytokines, particularly interleukin-6 (IL-6), which increase free iron by increasing ferritin levels due to increased synthesis and decreased iron transport. Also, concomitant acidosis increases free iron by reducing the ability of transferrin to chelate iron and this available iron becomes a considerable resource for mucormycosis. [1] Also, Mucorales adheres to and invades endothelial cells by specific recognition of the host receptor glucose-regulator protein 78 (GRP-78). Acidosis associated with severe COVID-19 triggers GRP-78 and fungal ligand spore coating homolog (CotH) protein expression on endothelial cells, both contributing to angioinvasion, hematogenous dissemination, and tissue necrosis. [2] CONCLUSIONS: Mucormycosis can present as spontaneous pneumothorax after recent COVID-19 and clinicians should be aware of rare clinical presentation. Reference #1: Singh AK, Singh R, Joshi SR, et al. Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes Metab Syndr Clin Res Rev 2021;15:102146. doi:10.1016/j.dsx.2021.05.019 Reference #2: Baldin C, Ibrahim AS. Molecular mechanisms of mucormycosis—The bitter and the sweet. PLOS Pathog 2017;13:e1006408. doi:10.1371/journal.ppat.1006408 DISCLOSURES: No relevant relationships by Faran Ahmad No relevant relationships by AYESHA BATOOL No relevant relationships by Zachary DePew No relevant relationships by Neil Mendoza
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Background: Anaemia and iron deficiency affect a high proportion of patients with cancer, especially when undergoing treatment with systemic anti-cancer therapies (SACT) and are associated with fatigue, reduced quality of life & reduced performance status. Over the past 4 years, the Oncology DTU has continuously reviewed the managment of patients with anaemia and in particular the need to diagnose iron deficiency at time of starting SACT and recently the same guidance were introduced for Haemato-Oncology patients. Routine blood testing of Transferrin Saturation (TSAT) and serum ferritin is performed on all patients at time of starting SACT, those diagnosed with iron deficiency anaemia are treated with an intravenous iron infusion. During this time, various logistical challenges, learning and updates to local guidance has led to a more robust process, now in place to manage this patient group. Methods: Cancer patients attending for cycle 1 day 1 SACT have their TSAT and serum ferritin levels measured, if diagnosed with iron deficiency (ie TSAT <20% and serum ferritin <100ug/L, patients will receive an intravenous iron infusion. In March 2022, an audit of 141 new oncology referrals for SACT and 11 patients who received a blood transfusion was conducted for compliance to local guidance. Results: Logistical challenges included: update and approval of local guidelines, education of all members of the Health Care Team re: prescribing, contraindications and side-effects of iron infusions, patient education. Wider issues, include: COVID, staffing. 129/141 patients had TSAT and serum ferritin levels checked, of these 57 patients were diagnosed as iron deficient, with 54 patients then receiving an iron infusion. Analysis of further results is still underway. Conclusions: Whilst this is a very small audit, it demonstrates the importance of considering iron deficiency as an underlying cause of anaemia in patients with cancer, who are starting SACT and can ensure patients receive the most appropriate supportive treatment for their needs. Through our experiences, with the support of our haematology consultant, this service is predominantly nurse led and continues to develop. Legal entity responsible for the study: The author. Funding: Has not received any funding. Disclosure: The author has declared no conflicts of interest.
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Background: Blood transfusions are common medical practice in the UK, with approximately 2.1 million blood products being issued by UK blood serices in 2020. The Serious Hazard of Transfusion (SHOT) scheme reported that the risk of death and serious harm related to transfusions was 1 in 53,193 and 1 in 15,142 in 2020, respectiely. Multiple complications can occur as a result of blood transfusions, with the most common cause of death being Transfusion Associated Circulatory Oerload (TACO). Although low risk, there has been an increase in deaths related to blood transfusions from 17 deaths in 2019, to 39 deaths in 2020, in the UK, with 81.6% of aderse reactions and eents being due to preentable errors. This stresses the importance of safe transfusion practice. Aims: To reiew the rates of blood transfusions from 2013 to 2021, and compare our adherence to NICE guidance. We analysed rates of transfusion, number of red blood cells (RBC) units per transfusion, haemoglobin leels and the incidence of iron deficiency anaemia (IDA) prior to transfusion. Methods: Data was collected retrospectiely from patients' records and the transfusion laboratory database at Surrey and Sussex healthcare Trust. Adults (>16 years old) who receied inpatient or outpatient RBC transfusions from 2013 to 2021 were included (n = 53,941). We looked in further detail at the RBC transfusions from the first 2 weeks of December from 2014 to 2021 (n=546). Results: Figure 1 shows that there has been a significant decline in the number of RBC transfused from 2014 to 2021;an aerage gradient of -36.25 units per year (R2= 0.72). There has also been a decline in the aerage number of units per blood transfusion, with a downward trendline (gradient -0.15 RBC units/year, p= 0.001). There has been a significant increase in the percentage of single unit transfusions from 14% in 2014 to 65% in 2021;the trendline has a gradient of +7% / year (p=0.0009). The aerage haemoglobin at initiation of transfusion has remained relatiely unchanged (69-78g/L), which is in line with NICE guidance. There is no improement in transfusion of patients with IDA;defined as a low transferrin saturation (<20%). The percentage of these patients being transfused arying from 43% to 79%, with no significant trend oer the years from 2014 to 2021 (p=0.71). Summary/Conclusion: The total number of RBC transfused has significantly decreased oer 9 years. Howeer, there is a slight rise from August 2020, which may hae been a result of expansion of the Hospital bed base from 697 to 800 between years 2018-2021. It also may hae been impacted by the COVID-19 pandemic. There is a decrease in the amount of RBC units transfused per patient. We are also encouraged to see a significant increase in the number of single unit transfusions, in line with NICE Guidance. We found there was no improement in the number of patients with IDA being transfused (aerage 64%). This indicates that, depending on the clinical scenario, some patients may be receiing unnecessary blood transfusions. They may benefit from receiing iron replacement as an alternatie treatment, thereby minimising exposing patients unnecessarily to the risks associated with blood transfusion. Appropriate management of IDA needs further work in the trust, and we hae initiated an IV iron serice oer the last 18 months to improe this. Limitations of this study include using two weeks of the year to extrapolate for each year and data may hae been skewed oer the last two years due to the COVID-19 pandemic.
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BACKGROUND: Nutritional deficiency is associated with weaken immune system and increased susceptibility to infection. Among other nutrients, several trace elements have been shown to regulate immune responses. Iron is one of the most abundant trace elements present in our body, which is required in various biological processes. Iron has an immunomodulatory function and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of different iron-related biomarkers in association to severity and mortality in SARS-CoV-2 patients. MATERIALS AND METHODS: A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate, and severe) and outcome (discharged or deceased). Serum iron, TIBC, ferritin, transferrin, transferrin saturation levels were analyzed by the direct colourimetric method. RESULTS: In cases the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 29 µg/dL, 132.53 µg/dL, 106.3 mg/dL, 17.74 % and 702.9 ng/dL respectively. Similarly, in controls the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 53 µg/dL, 391.88 µg/dL, 313.51 mg/dL, 12.81 % and 13.52 ng/dL respectively. On comparing the cases with the controls, a significant lower level of iron, TIBC, and transferrin were found in the cases along with the significant higher levels of ferritin and transferrin saturation. On comparing the Receiver operating characteristic (ROC) curves of Iron, Ferritin, Transferrin, Transferrin sat % and TIBC in relation to survival in COVID-19 patients it was found that iron, followed by transferrin and ferritin has the highest area under the curve (AUC) with 74 %, 63 % and 61 % respectively. Further, in pairwise analysis of ROC curve, a significant difference was found between the Iron-transferrin (p < 0.01), iron-TIBC (p < 0.001) and transferrin-ferritin (P < 0.01). The multiple regression model based on Iron and transferrin outperformed any other combination of variables via stepwise AIC selection with an AUC of 98.2 %. The cutoff point according to Youden's J index is characterized with a sensitivity of 98 % and a specificity of 96.8 %, indicating that iron along with transferrin can be a useful marker that may contribute to a better assessment of survival chances in COVID-19. CONCLUSION: Our study demonstrated a significantly decreased levels of iron, TIBC, & transferrin and a significantly increased levels of ferritin and transferrin saturation in COVID-19 patients when compared with controls. Further, Iron and transferrin were observed to be a good predictor of mortality in patients with COVID-19. From the above analysis we confirm that iron-related biomarkers play an important role in the development of oxidative stress and further lead to activation of the cytokine storm. So, continuous monitoring of these parameters could be helpful in the early detection of individuals developing the severe disease and can be used to decrease mortality in upcoming new waves of COVID-19.
Subject(s)
COVID-19 , Trace Elements , Biomarkers , Ferritins , Humans , Iron/metabolism , SARS-CoV-2 , TransferrinABSTRACT
GPs can play a pivotal role in the identification and management of alcohol problems at any time, and their role is even more important during the COVID-19 pandemic as more and more patients are resorting to alcohol to manage the stress and anxiety created by the pandemic. © 2021 Medicine Today Pty Ltd. All rights reserved.
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A positive association between anemia and all-cause mortality and cardiovascular mortality independent of age, gender, and history of cardiovascular diseases has been confirmed. Disturbed iron metabolism might also play a role in the prognosis of patients with COVID-19. Moreover, alterations of iron homeostasis can persist long after COVID-19 onset and could be associated with impaired physical performance. We aimed to evaluate the levels of parameters associated with iron metabolism in patients hospitalised with COVID-19 during a 1-week period. In our study, 53 patients were included and they were further divided into two groups according to the outcome: positive (recovery and discharge from hospital) or negative (aggravation, exitus, or both). Their blood samples were collected on Days 1, 3, and 7 during hospitalization and basic laboratory analyses were performed, including measurement of iron metabolism parameters. All patients had pathologically increased plasmatic levels of ferritin and decreased levels of transferrin during the whole observation period. We have not found any correlation between levels of these markers and patients' prognosis. However, levels of ferritin significantly decreased and levels of transferrin significantly increased on the seventh day only in patients with a positive outcome. Further studies with a longer observation period are warranted to evaluate the period needed for reestablishment of iron homeostasis. [ FROM AUTHOR] Copyright of Acta Facultatis Pharmaceuticae Universitatis Comenianae is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
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COVID-19 can cause detrimental effects on health. Vaccines have helped in reducing disease severity and transmission but their long-term effects on health and effectiveness against future viral variants remain unknown. COVID-19 pathogenesis involves alteration in iron homeostasis. Thus, a contextual understanding of iron-related parameters would be very valuable for disease prognosis and therapeutics.Accordingly, we reviewed the status of iron and iron-related proteins in COVID-19. Iron-associated alterations in COVID-19 reported hitherto include anemia of inflammation, low levels of serum iron (hypoferremia), transferrin and transferrin saturation, and high levels of serum ferritin (hyperferritinemia), hepcidin, lipocalin-2, catalytic iron, and soluble transferrin receptor (in ICU patients). Hemoglobin levels can be low or normal, and compromised hemoglobin function has been proposed. Membrane-bound transferrin receptor may facilitate viral entry, so it acts as a potential target for antiviral therapy. Lactoferrin can provide natural defense by preventing viral entry and/or inhibiting viral replication. Serum iron and ferritin levels can predict COVID-19-related hospitalization, severity, and mortality. Serum hepcidin and ferritin/transferrin ratio can predict COVID-19 severity. Here, serum levels of these iron-related parameters are provided, caveats of iron chelation for therapy are discussed and the interplay of these iron-related parameters in COVID-19 is explained.This synopsis is crucial as it clearly presents the iron picture of COVID-19. The information may assist in disease prognosis and/or in formulating iron-related adjunctive strategies that can help reduce infection/inflammation and better manage COVID-19 caused by future variants. Indeed, the current picture will augment as more is revealed about these iron-related parameters in COVID-19.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the reason behind the third zoonotic outbreak from the Coronaviridae family during the 21st century. COVID-19 was declared a pandemic by the WHO on 11 March 2020, and it has been posing a challenge for the health care system all around the world. Research groups worldwide are trying to find potential leads for drugs against SARS-CoV-2. Investigating natural products and extracts from known medicinal plants has been one area of focus in searching for potential inhibitors of SARS-CoV-2. This review aims to highlight the importance of including natural plants and plants derived compounds in this investigation. We particularly focused on compounds from Artemisia species (artemisinin and its derivatives), as this plant is highly valuable and has various pharmacological profiles.
ABSTRACT
Rationale: Cell-penetrating peptides are able to cross membranes and deliver cargoes in a functional form. Our prior work identified a 12-amino acid, cardiac targeting peptide (APWHLSSQYSRT). Studies into its mechanism of transduction led to the identification of two lung targeting peptides (LTPs), S7A and R11A. Here we report on a) the comparative lung uptake of S7A versus R11A, b) complete biodistribution of R11A, c) show that cyclic versions are -100-fold more efficient than linear counterparts, d) uptake is via a non-endocytic pathway, and e) cyclic R11A's (cR11A) ability to deliver siRNA targeting structural proteins of SARS-CoV-2 and act as an anti-viral. Methods: Linear LTPs were synthesized with N-terminal labeled with Cyanine 5.5 (Cy5.5). Cyclic versions were synthesized with lysine added to the N-terminus, cyclized through a peptide bond, with a side NH-group labeled with Cy5.5. cR11A was conjugated to siRNA duplexes via a DTME linker. Wild-type, CD1 mice, were injected with S7A or R11A at 10, 5, and 1mg/Kg, peptides allowed to circulate for 15mins, mice euthanized, lung along with multiple other organs dissected and imaged using In Vivo Imaging Systems (IVIS, Perkin-Elmer) followed by confocal microscopy. CD1 mice were injected with R11A, 5mg/Kg, and euthanized at different time intervals for biodistribution studies. Endocytosis studies were done using serum-starved human bronchial epithelial cells (HBEC) incubated with fluorescently labeled transferrin and LTP-S7A or LTP- R11A. Lastly, anti-viral activity was tested in HBECs pre-treated with cR11A-siRNA followed by viral infection. Results: Mice injected with LTP-S7A or LTP-R11A showed robust uptake of the peptides by lung tissue, with R11A showing an increasingly favorable lung:liver ratio with decreasing dose. Lung uptake of R11A peaked at 120mins with complete dissipation of fluorescence by 24 hours. In Vitro studies in HBECs showed no co-localization of transferrin with LTPs, ruling out endocytosis as a mechanism of uptake. Comparison of linear versus cyclic peptides using FACS showed cyclic peptides had -100-fold increased transduction efficiency over their linear counterparts. cR11A conjugated to ant-spike, and anti-envelop proteins showed an anti-viral effect with EC90 of 0.6uM and 1.0μM, respectively. Conclusions: We have identified two novel lung-targeting peptides capable of acting as delivery vectors. Peak uptake of R11A occurred at 120mins. Furthermore, this uptake was not via endocytosis, and cyclic versions were -100-fold more efficiently taken up. Lastly, as proof of concept, we show cR11A acts as a vector and delivers siRNA to HBECs in a functional form, and act as anti-virals.