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1.
Int J Mol Sci ; 21(21)2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33153161

RESUMO

Progressive respiratory failure is seen as a major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection. Relatively little is known about the associated morphologic and molecular changes in the circulation of these patients. In particular, platelet and erythrocyte pathology might result in severe vascular issues, and the manifestations may include thrombotic complications. These thrombotic pathologies may be both extrapulmonary and intrapulmonary and may be central to respiratory failure. Previously, we reported the presence of amyloid microclots in the circulation of patients with coronavirus disease 2019 (COVID-19). Here, we investigate the presence of related circulating biomarkers, including C-reactive protein (CRP), serum ferritin, and P-selectin. These biomarkers are well-known to interact with, and cause pathology to, platelets and erythrocytes. We also study the structure of platelets and erythrocytes using fluorescence microscopy (using the markers PAC-1 and CD62PE) and scanning electron microscopy. Thromboelastography and viscometry were also used to study coagulation parameters and plasma viscosity. We conclude that structural pathologies found in platelets and erythrocytes, together with spontaneously formed amyloid microclots, may be central to vascular changes observed during COVID-19 progression, including thrombotic microangiopathy, diffuse intravascular coagulation, and large-vessel thrombosis, as well as ground-glass opacities in the lungs. Consequently, this clinical snapshot of COVID-19 strongly suggests that it is also a true vascular disease and considering it as such should form an essential part of a clinical treatment regime.


Assuntos
Plaquetas/patologia , Doenças Cardiovasculares/virologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Eritrócitos/patologia , Ferritinas/sangue , Selectina-P/sangue , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , Coagulação Sanguínea/fisiologia , Plaquetas/virologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/patologia , Infecções por Coronavirus/virologia , Eritrócitos/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Trombose/patologia , Trombose/virologia
2.
Respir Res ; 21(1): 276, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087116

RESUMO

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is frequently associated with hyperinflammation and hyperferritinemia. The latter is related to increased mortality in COVID-19. Still, it is not clear if iron dysmetabolism is mechanistically linked to COVID-19 pathobiology. METHODS: We herein present data from the ongoing prospective, multicentre, observational CovILD cohort study (ClinicalTrials.gov number, NCT04416100), which systematically follows up patients after COVID-19. 109 participants were evaluated 60 days after onset of first COVID-19 symptoms including clinical examination, chest computed tomography and laboratory testing. RESULTS: We investigated subjects with mild to critical COVID-19, of which the majority received hospital treatment. 60 days after disease onset, 30% of subjects still presented with iron deficiency and 9% had anemia, mostly categorized as anemia of inflammation. Anemic patients had increased levels of inflammation markers such as interleukin-6 and C-reactive protein and survived a more severe course of COVID-19. Hyperferritinemia was still present in 38% of all individuals and was more frequent in subjects with preceding severe or critical COVID-19. Analysis of the mRNA expression of peripheral blood mononuclear cells demonstrated a correlation of increased ferritin and cytokine mRNA expression in these patients. Finally, persisting hyperferritinemia was significantly associated with severe lung pathologies in computed tomography scans and a decreased performance status as compared to patients without hyperferritinemia. DISCUSSION: Alterations of iron homeostasis can persist for at least two months after the onset of COVID-19 and are closely associated with non-resolving lung pathologies and impaired physical performance. Determination of serum iron parameters may thus be a easy to access measure to monitor the resolution of COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04416100.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Homeostase , Ferro/metabolismo , Pneumopatias/etiologia , Pneumopatias/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Adulto , Idoso , Anemia/etiologia , Proteína C-Reativa/análise , Estudos de Coortes , Infecções por Coronavirus/fisiopatologia , Feminino , Ferritinas/sangue , Seguimentos , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Interleucina-6/sangue , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Pandemias , Pneumonia Viral/fisiopatologia , Estudos Prospectivos , Tomografia Computadorizada por Raios X
3.
J Clin Lab Anal ; 34(10): e23618, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33078400

RESUMO

OBJECTIVE: The coronavirus disease 2019 (COVID-19) has rapidly developed into a pandemic. Increased levels of ferritin due to cytokine storm and secondary hemophagocytic lymphohistiocytosis were found in severe COVID-19 patients. Therefore, the aim of this study was to determine the role of ferritin in COVID-19. METHODS: Studies investigating ferritin in COVID-19 were collected from PubMed, EMBASE, CNKI, SinoMed, and WANFANG. A meta-analysis was performed to compare the ferritin level between different patient groups: non-survivors versus survivors; more severe versus less severe; with comorbidity versus without comorbidity; ICU versus non-ICU; with mechanical ventilation versus without mechanical ventilation. RESULTS: A total of 52 records involving 10 614 COVID-19-confirmed patients between December 25, 2019, and June 1, 2020, were included in this meta-analysis, and 18 studies were included in the qualitative synthesis. The ferritin level was significantly increased in severe patients compared with the level in non-severe patients [WMD 397.77 (95% CI 306.51-489.02), P < .001]. Non-survivors had a significantly higher ferritin level compared with the one in survivors [WMD 677.17 (95% CI 391.01-963.33), P < .001]. Patients with one or more comorbidities including diabetes, thrombotic complication, and cancer had significantly higher levels of ferritin than those without (P < .01). Severe acute liver injury was significantly associated with high levels of ferritin, and its level was associated with intensive supportive care, including ICU transfer and mechanical ventilation. CONCLUSIONS: Ferritin was associated with poor prognosis and could predict the worsening of COVID-19 patients.


Assuntos
Infecções por Coronavirus , Ferritinas/sangue , Pandemias , Pneumonia Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Prognóstico
4.
J Med Case Rep ; 14(1): 187, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33054818

RESUMO

BACKGROUND: The understanding of coronavirus disease 2019 (COVID-19) is rapidly evolving. Although it is primarily a respiratory illness, other manifestations, such as Guillain-Barré syndrome, immune thrombocytopenia, and immune-mediated thrombotic thrombocytopenic purpura, have been described. We present a case of a patient with hemophagocytic lymphohistiocytosis secondary to COVID-19 treated with tocilizumab with a marked biochemical improvement. CASE PRESENTATION: In this case report we present a Caucasian patient with COVID-19 who developed a marked elevation of inflammatory parameters with ferritin 36,023 µg/L, but also elevated C-reactive protein 334 mg/L and lactate dehydrogenase 1074 U/L, 1 week after admission to the intensive care unit. He met five of eight criteria for hemophagocytic lymphohistiocytosis, but he lacked the high fever and cytopenia seen in the majority of cases. He was treated with tocilizumab, a monoclonal antibody targeting the interleukin-6 receptor, and over the next days, a rapid decrease in ferritin and C-reactive protein levels was observed. However, his respiratory failure only improved gradually, and he was weaned off the respirator 11 days later. CONCLUSION: COVID-19 may induce a hyperinflammatory clinical picture and in some cases develop into hemophagocytic lymphohistiocytosis. In our patient's case, therapeutic interleukin-6 blockade abrogated signs of hyperinflammation but did not seem to improve pulmonary function. Measurement of ferritin and C-reactive protein, as well as quantification of interleukin-6 on indication, should be performed in patients with severe COVID-19. Specific treatment in such patients must also be contemplated, preferably in randomized controlled trials.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus , Inflamação/sangue , Interleucina-6 , Pandemias , Pneumonia Viral , Idoso , Anticorpos Monoclonais/administração & dosagem , Proteína C-Reativa/análise , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Ferritinas/sangue , Humanos , Interleucina-6/análise , Interleucina-6/antagonistas & inibidores , Linfo-Histiocitose Hemofagocítica/etiologia , Masculino , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Respiração Artificial/métodos , Resultado do Tratamento
5.
Clin Lab ; 66(9)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32902237

RESUMO

BACKGROUND: Real-time reverse transcription polymerase chain reaction assay (RT-PCR) is the gold standard for diagnosis of coronavirus disease 2019 (COVID-19); however, it is not universally available and may have limitations in response times. The aim was to evaluate the routine blood tests for diagnosis of COVID-19, determining the diagnostic accuracy of blood biomarkers to differentiate between patients with and without COVID-19. METHODS: Clinical charts, nursing records, laboratory findings, and chest x-rays from adult patients with clinical suspicion of COVID-19 (fever, cough and/or dyspnea) at hospital admission were reviewed. Patients were classified into two groups according to RT-PCR COVID-19: positive (COVID-19) or negative (NON-COVID-19). Diagnostic accuracy was determined by analyzing receiver operating characteristic (ROC) curve, calculating the area under the ROC curve (AUC) and the cutoff value. In order to reduce the number of false positives, the cutoff value with a specificity of 80% was considered. RESULTS: Two hundred three patients (101 females, 102 males) with ages between 18 and 96 years (mean = 61.3) were studied. Ninety-four were COVID-19 and 109 were NON-COVID-19. Plasma ferritin level was the most accurate biomarker (AUC = 0.847 and 0.804 in women and men, respectively). The following diagnostic criteria for suspected COVID-19 were established with biomarker cutoff values to differentiate between COVID-19 and NON-COVID-19 patients: lymphocytes ≤ 1.0 x 109/L; eosinophils ≤ 0.02 x 109/L; ferritin > 125% of upper reference limit (URL); LDH > 125% of URL; hsCRP > 80 mg/L; and D-dimer > 1.2 mg/L. Sensitivity was 66%, 64% 62%, 46%, 43%, and 33% for ferritin, eosinophils, LDH, hsCRP, lymphocytes, and D-dimer, respectively. Of those determined to be COVID-19 patients, 91% met one or more of the diagnostic criteria with these blood biomarkers, and of the NON-COVID-19 patients, 47% did not met any diagnostic criteria. CONCLUSIONS: Blood counts of lymphocytes and eosinophils, and plasma levels of D-dimer, LDH, hsCRP, and ferritin can be used to differentiate patients with and without COVID-19 and as a tool for diagnosis of suspected COVID-19 in adult patients at hospital admission.


Assuntos
Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos Transversais , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , L-Lactato Desidrogenase/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Espanha , Adulto Jovem
6.
PLoS One ; 15(9): e0239192, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32986748

RESUMO

BACKGROUND: Few studies have evaluated iron-rich plant-based foods, such as amaranth grain, to reduce anemia and iron deficiency anemia. Amaranth is rich in nutrients, but with high level of phytate. The objective of this trial was to evaluate the efficacy of home processed amaranth grain containing bread in the treatment of anemia, hemoglobin concentration and iron deficiency anemia among two-to-five year-old children in Southern Ethiopia. METHOD: Children with anemia (hemoglobin concentration <110.0g/L) (N = 100) were identified by random sampling and enrolled in a 1:1 cluster randomized controlled trial for six months in 2017. The amaranth group (N = 50), received 150g bread containing 70% amaranth and 30% chickpea, the amaranth grain was processed at home (soaking, germinating, and fermenting) to decrease the phytate level. The maize group (N = 50), received 150g bread, containing processed maize (roasted and fermented) to give a similar color and structure with amaranth bread. Hemoglobin, ferritin, and CRP were measured at baseline and at the end of intervention. Hemoglobin and ferritin values were adjusted for altitude and infection, respectively. Generalized estimating equation and generalized linear model were used to analyze the data. RESULT: In the last follow-up measure anemia prevalence was significantly lower in the amaranth group (32%) as compared with the maize group (56%) [adjusted risk ratios, aRR: 0.39 (95%CI: 0.16-0.77)]. Hemoglobin concentration estimate of beta coefficient was significantly higher in the amaranth group compared with the maize group [aß 8.9g/L (95%CI: 3.5-14.3)], p-value <0.01. The risk of iron deficiency anemia is significantly lower in the amaranth group [aRR: 0.44 (95%CI: 0.23-0.83)] in the intention to treat analysis but not significant in the complete case analysis. There was no significant difference between groups in iron deficiency [aRR: 0.81 (95%CI: 0.55-1.19)]. CONCLUSION: Processed amaranth bread had favorable effects on hemoglobin concentration and has the potential to minimize anemia prevalence. CLINICAL TRIAL REGISTRATION: Trial registry number: PACTR201705002283263 https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=2283.


Assuntos
Amaranthus , Anemia Ferropriva/dietoterapia , Pão , Ferro/metabolismo , Zea mays , Pré-Escolar , Suplementos Nutricionais , Etiópia , Feminino , Ferritinas/sangue , Alimentos Fortificados , Alimento Funcional , Hemoglobinas/análise , Humanos , Ferro/deficiência , Masculino
8.
Med Sci Monit ; 26: e926178, 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32978363

RESUMO

BACKGROUND The aim of this study was to assess the diagnostic utility of iron homeostasis determinations for prediction of severity of COVID-19. MATERIAL AND METHODS This was a retrospective study enrolling a total of 50 patients diagnosed with the novel coronavirus disease-19 (COVID-19) from February 27, 2020 to March 30, 2020, including a severe group (12 patients) and a mild group (38 patients). For the control group, 50 healthy people were examined during the same period. We compared clinical laboratory data and iron homeostasis biomarkers among the 3 groups. ROC curve analysis was used to assess diagnoses. RESULTS Patients diagnosed with severe COVID-19 had higher hepcidin and serum ferritin levels than in other groups (p<0.001). A combination test of hepcidin and serum ferritin provided the best specificity and sensitivity in the prognosis of COVID-19 severity. Logistic regression analysis showed hepcidin and serum ferritin independently contributed to the severity of COVID-19. Hepcidin and serum ferritin tandem testing predicted COVID-19 severity with 94.6% specificity, while hepcidin and serum ferritin parallel testing had a sensitivity of 95.7%. CONCLUSIONS Iron homeostasis had a robust association with the occurrence of severe COVID-19. Iron homeostasis determinations were specific and sensitive for the early prediction of disease severity in COVID-19 patients and thus have clinical utility.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Ferritinas/sangue , Hepcidinas/sangue , Pandemias , Pneumonia Viral/sangue , Adulto , Idoso , Área Sob a Curva , Biomarcadores , Feminino , Homeostase , Humanos , Ferro/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
9.
J Int Med Res ; 48(9): 300060520955037, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32960106

RESUMO

BACKGROUND: The roles of inflammation and hypercoagulation in predicting outcomes of coronavirus disease 2019 (COVID-19) are unclear. METHODS: Adult patients diagnosed with COVID-19 from 28 January 2020 to 4 March 2020 in Tongji Hospital, Wuhan were recruited. Data on related parameters were collected. Univariate analysis and multivariable binary logistic regression were used to explore predictors of critical illness and mortality. RESULTS: In total, 199 and 44 patients were enrolled in the training and testing sets, respectively. Elevated ferritin, tumor necrosis factor-α and D-dimer and decreased albumin concentration were associated with disease severity. Older age, elevated ferritin and elevated interleukin-6 were associated with 28-day mortality. The FAD-85 score, defined as age + 0.01 * ferritin +D-dimer, was used to predict risk of mortality. The sensitivity, specificity and accuracy of FAD-85 were 86.4%, 81.8% and 86.4%, respectively. A nomogram was established using age, ferritin and D-dimer to predict the risk of 28-day mortality. CONCLUSIONS: Thrombo-inflammatory parameters provide key information on the severity and prognosis of COVID-19 and can be used as references for clinical treatment to correct inflammatory and coagulation abnormalities.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/mortalidade , Coagulação Intravascular Disseminada/mortalidade , Pneumonia Viral/mortalidade , Trombose/mortalidade , Adulto , Idoso , Biomarcadores/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Coagulação Intravascular Disseminada/complicações , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/virologia , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Interleucina-6/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Prognóstico , Projetos de Pesquisa , Estudos Retrospectivos , Albumina Sérica/metabolismo , Índice de Gravidade de Doença , Análise de Sobrevida , Trombose/complicações , Trombose/diagnóstico , Trombose/virologia , Fator de Necrose Tumoral alfa/sangue
10.
Neurol Sci ; 41(11): 3031-3038, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32935157

RESUMO

BACKGROUND: COVID-19 disease affects the nervous system and led to an increase in neurological consults for patients at admission and through the period of hospitalization during the peak of the pandemic. METHODS: Patients with clinical and laboratory diagnosis of COVID-19 that required a neurologic consultation or those who presented with neurological problems on admission that led to a diagnosis of SARS-CoV-2 infection during a 2-month period at the peak of the pandemic were included in this study. Demographic and clinical variables were analyzed. RESULTS: Thirty-five patients were included. The presenting neurologic manifestations on admission led to the diagnosis of COVID-19 in 14 patients (40%). The most common reasons for consultation during the hospitalization period were stroke (11), encephalopathy (7), seizures (6), and neuropathies (5) followed by a miscellaneous of syncope (2), migraine (1), anosmia (1), critical illness myopathy (1), and exacerbation of residual dysarthria (1). The most common neurological disturbances were associated with severe disease except for neuropathies. Patients with encephalopathies and seizures had markedly increased D-dimer and ferritin values, even higher than stroke patients. RT-PCR was performed in 8 CSF samples and was negative in all of them. CONCLUSION: Neurological disturbances represent a significant and severe burden in COVID-19 patients, and they can be the presenting condition that leads to the diagnosis of the viral infection in a high percentage of patients. Evidence of direct viral mechanisms was scarce, but the pathogenesis of the diverse manifestations remains enigmatic.


Assuntos
Infecções por Coronavirus/complicações , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/virologia , Pneumonia Viral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Biomarcadores/sangue , Proteína C-Reativa/análise , Infecções por Coronavirus/sangue , Estudos Transversais , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/sangue , Pandemias , Pneumonia Viral/sangue , Encaminhamento e Consulta , Adulto Jovem
13.
Interv Neuroradiol ; 26(5): 623-628, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32862753

RESUMO

BACKGROUND: This study evaluates the mortality risk of patients with emergent large vessel occlusion (ELVO) and COVID-19 during the pandemic. METHODS: We performed a retrospective cohort study of two cohorts of consecutive patients with ELVO admitted to a quaternary hospital from March 1 to April 17, 2020. We abstracted data from electronic health records on baseline, biomarker profiles, key time points, quality measures and radiographic data. RESULTS: Of 179 patients admitted with ischemic stroke, 36 had ELVO. Patients with COVID-19 and ELVO had a higher risk of mortality during the pandemic versus patients without COVID-19 (OR 16.63, p = 0.004). An age-based sub-analysis showed in-hospital mortality in 60% of COVID-19 positive patients between 61-70 years-old, 66.7% in between 51-60 years-old, 50% in between 41-50 years-old and 33.3% in between 31-40 years old. Patients that presented with pulmonary symptoms at time of stroke presentation had 71.4% mortality rate. 27.3% of COVID-19 patients presenting with ELVO had a good outcome at discharge (mRS 0-2). Patients with a history of cigarette smoking (p = 0.003), elevated d-dimer (p = 0.007), failure to recanalize (p = 0.007), and elevated ferritin levels (p = 0.006) had an increased risk of mortality. CONCLUSION: Patients with COVID-19 and ELVO had a significantly higher risk for mortality compared to COVID-19 negative patients with ELVO. A small percentage of COVID-19 ELVO patients had good outcomes. Age greater than 60 and pulmonary symptoms at presentation have higher risk for mortality. Other risk factors for mortality were a history of cigarette smoking, elevated, failure to recanalize, elevated d-dimer and ferritin levels.


Assuntos
Arteriopatias Oclusivas/mortalidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Mortalidade Hospitalar , Humanos , Pneumopatias/etiologia , Pneumopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Pandemias , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fumar/mortalidade , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Resultado do Tratamento
14.
PLoS Negl Trop Dis ; 14(9): e0008711, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32997666

RESUMO

Environmental enteric dysfunction (EED) is an intestinal disorder common among children in low-resource settings and is associated with increased risk of growth stunting, cognitive deficits, and reduced oral vaccine immunogenicity. The Micronutrient and EED Assessment Tool (MEEDAT) is a multiplexed immunoassay that measures biomarkers previously associated with child growth faltering and/or oral vaccine immunogenicity: intestinal fatty acid-binding protein (I-FABP), soluble CD14 (sCD14), insulin-like growth factor 1 (IGF-1), and fibroblast growth factor 21 (FGF21). MEEDAT also measures systemic inflammation (α1-acid glycoprotein, C-reactive protein), ferritin, soluble transferrin receptor, retinol binding protein 4, thyroglobulin, and Plasmodium falciparum antigenemia (histidine-rich protein 2). The performance of MEEDAT was compared with commercially available enzyme-linked immunosorbent assays (ELISAs) using 300 specimens from Malian infant clinical trial participants. Regression methods were used to test if MEEDAT biomarkers were associated with seroconversion to meningococcal A conjugate vaccine (MenAV), yellow fever vaccine (YFV), and pentavalent rotavirus vaccine (PRV) after 28 days, or with growth faltering over 12 weeks. The Pearson correlations between the MEEDAT and ELISA results were 0.97, 0.86, 0.80, and 0.97 for serum I-FABP, sCD14, IGF-1, and FGF21, respectively. There were significant associations between I-FABP concentration and the probability of PRV IgG seroconversion and between IGF-1 concentration and the probability of YFV seroconversion. In multivariable models neither association remained significant, however there was a significant negative association between AGP concentration and YFV seroconversion. GLP-2 and sCD14 concentrations were significantly negatively associated with 12-week change in weight-for-age z-score and weight-for-height z-score in multivariable models. MEEDAT performed well in comparison to commercially-available ELISAs for the measurement of four analytes for EED and growth hormone resistance. Adoption of MEEDAT in low-resource settings could help accelerate the identification of interventions that prevent or treat child stunting and interventions that boost the immunogenicity of child vaccinations.


Assuntos
Imunogenicidade da Vacina/imunologia , Enteropatias/imunologia , Micronutrientes/imunologia , Vacinas/imunologia , Vacina contra Febre Amarela/imunologia , Febre Amarela/imunologia , Febre Amarela/prevenção & controle , Biomarcadores/sangue , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Proteínas de Ligação a Ácido Graxo , Feminino , Ferritinas/sangue , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Lactente , Inflamação , Fator de Crescimento Insulin-Like I/metabolismo , Intestino Delgado , Receptores de Lipopolissacarídeos , Masculino , Mali , Proteínas Plasmáticas de Ligação ao Retinol , Fatores de Risco , Vacinação
15.
Ann Hematol ; 99(11): 2507-2512, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32918595

RESUMO

Iron overload comprises one of the main complications of congenital dyserythropoietic anemia type I (CDA-I). When analyzing magnetic resonance imaging T2* (MRI T2*) results in CDA patients, two previous studies reported discordant results regarding iron load in these patients. To further understand iron loading pattern in this group of patients, we analyzed MRI T2* findings in 46 CDA-I patients. Mild to moderate hepatic iron overload was detected in 28/46 (60.8%) patients. A significant correlation was found between serum ferritin and liver iron concentration (LIC). A significant correlation (p value = 0.02) was also found between the patient's age and LIC, reflecting increased iron loading over time, even in the absence of transfusion therapy. Notably, no cardiac iron overload was detected in any patient. Transfusion-naive patients had better LIC and better cardiac T2* values. These results demonstrate that a high percentage of CDA-I patients have liver iron concentration above the normal values, risking them with significant morbidity and mortality, and emphasize the importance of periodic MRI T2* studies for direct assessment of tissue iron concentration in these patients, taking age and transfusional burden into consideration.


Assuntos
Anemia Diseritropoética Congênita , Sobrecarga de Ferro , Ferro/sangue , Fígado , Imagem por Ressonância Magnética , Miocárdio/metabolismo , Adolescente , Adulto , Anemia Diseritropoética Congênita/sangue , Anemia Diseritropoética Congênita/diagnóstico por imagem , Criança , Pré-Escolar , Ferritinas/sangue , Seguimentos , Humanos , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/diagnóstico por imagem , Fígado/diagnóstico por imagem , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
PLoS One ; 15(9): e0236277, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877424

RESUMO

Patients with high serum ferritin and low transferrin saturation (TSAT) levels could be considered as presenting with dysutilization of iron for erythropoiesis. However, the long-term safety of iron administration in these patients has not been well established. An observational multicenter study was performed over 3 years. In 805 patients undergoing maintenance hemodialysis (MHD), we defined dysutilization of iron for erythropoiesis in patients with lower TSAT (<20%) and higher ferritin (≥100 ng/mL) levels. A time-dependent Cox hazard model was used for the evaluation of the association between dysutilization of iron for erythropoiesis and adverse events and survival. Patients with low TSAT levels showed an increased risk of cerebrovascular and cardiovascular disease (CCVD) and death compared to patients with normal or higher TSAT levels. Patients with low ferritin and high TSAT levels had a significantly lower risk of CCVD and death compared with patients with high ferritin and low TSAT levels. Higher TSAT levels were associated with male gender, age, the absence of diabetes, low levels of high-sensitivity CRP, and low ß2 microglobulin levels, but not with intravenous iron administration or ferritin levels. Although patients with low TSAT levels had a significantly higher risk of CCVD or death, high TSAT levels were not linked with iron administration. Patients, who were suspected of dysutilization of iron for erythropoiesis, had a higher risk of CCVD and death. The administration of iron should be performed cautiously for improving TSAT levels, as iron administration could sustain TSAT levels for a short term.


Assuntos
Doenças Cardiovasculares/sangue , Transtornos Cerebrovasculares/sangue , Ferritinas/sangue , Diálise Renal , Transferrina/análise , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/etiologia , Feminino , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Diálise Renal/efeitos adversos , Fatores de Risco
17.
Medicine (Baltimore) ; 99(31): e21419, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756143

RESUMO

Both total-body iron stores and inflammation influence the concentration of ferritin in the blood. Ferritin as an inflammatory marker might serve as a prognostic marker in the elderly. Therefore, we characterized the clinical circumstances and long-term outcomes of hyperferritinemia (> 1000 µg/L) in hospitalized elderly patients.A retrospective analysis of elderly (> 70 years) inpatients with ferritin levels of > 1000 µg/L in a tertiary medical center during a 3-year period. We obtained both laboratory and clinical data, assessing the potential association of high ferritin levels with long-term mortality.Overall, 242 patients (median age 79 years; median ferritin level 1436 µg/L) met the inclusion criteria and were followed for a median time of 18.6 months. Clinical outcomes were dismal for the whole cohort: the diagnosis of solid malignancy occurred in 23.5% of cases while 31% had a severe infection (ranging from sepsis to septic shock). The median survival time of the whole cohort was 4.7 months only. Within the cohort, risk stratification was feasible: higher ferritin levels differentiate between groups of patients who had a poor prognosis (with either septic shock or solid malignancy) and those who had a relatively favorable prognosis (patients diagnosed as suffering from sepsis without shock and patients with iatrogenic causes for hyperferritinemia).Hyperferritinemia in elderly inpatients is associated with high rates of mortality. Within this group of patients, differential ferritin levels enable further risk stratification. High ferritin levels in the elderly can differentiate the bad from the worst.


Assuntos
Ferritinas/sangue , Idoso Fragilizado , Hospitalização , Sobrecarga de Ferro/mortalidade , Idoso , Biomarcadores/sangue , Estudos de Coortes , Serviços de Saúde para Idosos , Humanos , Sobrecarga de Ferro/sangue , Israel , Estudos Retrospectivos , Índice de Gravidade de Doença
18.
Ann Hematol ; 99(10): 2265-2277, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32803313

RESUMO

ß-Thalassemia is an inherited single gene disorder related to reduced synthesis of the ß-globin chain of hemoglobin. Patients with ß-thalassemia present variable clinical severity ranging from asymptomatic trait to severe transfusion-dependent anemia and multiple organs complications. Moreover, multiple immune abnormalities are a major concern in ß-thalassemia patients. Aberrant neutrophil effector function plays a pivotal role in infection susceptibility in these patients. In severe and persistent inflammation, immature neutrophils are released from the bone marrow and are functionally different compared with mature ones. Despite some abnormalities reported for thalassemia patient's immune system, few data exist on the characterization of human neutrophils in ß-thalassemia. The aim of this study was to investigate the phenotype and function of circulating neutrophil subsets in patients with ß-thalassemia major and with ß-thalassemia intermedia divided in transfusion-dependent and non-transfusion-dependent. By the use of immunochemical and cytofluorimetric analyses, we observed that patients' CD16+ neutrophils exhibit abnormalities in their phenotype and functions and the abnormalities vary according to the clinical form of the disease and to the neutrophil subset (CD16bright and CD16dim). Abnormalities include altered surface expression of the innate immune receptor CD45, Toll-like receptor 4, and CD32, reduced ability to produce an oxidative burst, and elevated levels of membrane lipid peroxidation, especially in patients with a more severe form of the disease. Overall, our results indicating the occurrence of an immuno-senescent phenotype on circulating neutrophils from thalassemia patients suggest the usefulness of neutrophil feature assessment as a tool for better clinical management of ß-thalassemia.


Assuntos
Neutrófilos/imunologia , Talassemia beta/sangue , Adulto , Antígenos CD/sangue , Transfusão de Componentes Sanguíneos , Senescência Celular , Terapia por Quelação , Feminino , Ferritinas/sangue , Humanos , Imunofenotipagem , Quelantes de Ferro/uso terapêutico , Contagem de Leucócitos , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Ativação de Neutrófilo , Neutrófilos/química , Neutrófilos/classificação , Explosão Respiratória , Esplenectomia , Receptor 4 Toll-Like/sangue , Adulto Jovem , Talassemia beta/imunologia , Talassemia beta/terapia
19.
Am J Case Rep ; 21: e925849, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32804917

RESUMO

BACKGROUND Pneumonia caused by coronavirus originated in Wuhan, China in late 2019 and has spread around the world, becoming a pandemic. Many patients deteriorate rapidly and require intubation and mechanical ventilation, which is causing the collapse of healthcare systems in many countries. Coronavirus infection is associated with extensive lung inflammation and microvascular thrombosis, which can result in hypoxia. It can also cause severe and lasting harm in other organs, including the heart and kidneys. At present, there is no proven and efficacious treatment for this new disease. Consequently, there is a growing tendency to use novel methods. Ozone therapy consists of administration of a mixture of oxygen and ozone (a molecule consisting of 3 oxygen atoms). The potential benefits of this therapy include reduced tissue hypoxia, decreased hypercoagulability, renal and heart protection, modulated immune function, improved phagocytic function, and impaired viral replication. CASE REPORT We report rapidly improved hypoxia with associated decreases in inflammatory markers and D-dimer immediately after 1-4 sessions of oxygen-ozone (O2-O3) therapy in 3 patients with COVID-19 pneumonia who presented with respiratory failure. Invasive mechanical ventilation was not required in these 3 patients. All patients were discharged home on days 3-4 after O2-O3 therapy. CONCLUSIONS O2-O3 therapy appears to be an effective therapy for COVID-19 patients with severe respiratory failure. Large controlled clinical trials are required to study the efficacy and safety of using O2-O3 therapy compared with the standard supportive case in patients with COVID-19 in terms of the need for invasive ventilation and length of hospital and intensive care unit stays.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Oxigênio/uso terapêutico , Ozônio/uso terapêutico , Pneumonia Viral/terapia , Transfusão de Sangue Autóloga , Proteína C-Reativa/análise , Infecções por Coronavirus/diagnóstico , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Hipóxia/terapia , Hipóxia/virologia , Infusões Intravenosas , L-Lactato Desidrogenase/sangue , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Radiografia , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia
20.
Eur J Epidemiol ; 35(8): 763-773, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32816244

RESUMO

Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and erythrocyte indices) in patients diagnosed with COVID-19, and explored their prognostic value. Six bibliographic databases were searched up to August 3rd 2020. We included 189 unique studies, with data from 57,563 COVID-19 patients. Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 129.7 g/L (95% Confidence Interval (CI), 128.51; 130.88) and 777.33 ng/mL (95% CI, 701.33; 852.77), respectively. Hemoglobin levels were lower with older age, higher percentage of subjects with diabetes, hypertension and overall comorbidities, and admitted to intensive care. Ferritin level increased with older age, increasing proportion of hypertensive study participants, and increasing proportion of mortality. Compared to moderate cases, severe COVID-19 cases had lower hemoglobin [weighted mean difference (WMD), - 4.08 g/L (95% CI - 5.12; - 3.05)] and red blood cell count [WMD, - 0.16 × 1012 /L (95% CI - 0.31; - 0.014)], and higher ferritin [WMD, - 473.25 ng/mL (95% CI 382.52; 563.98)] and red cell distribution width [WMD, 1.82% (95% CI 0.10; 3.55)]. A significant difference in mean ferritin levels of 606.37 ng/mL (95% CI 461.86; 750.88) was found between survivors and non-survivors, but not in hemoglobin levels. Future studies should explore the impact of iron metabolism and anemia in the pathophysiology, prognosis, and treatment of COVID-19.


Assuntos
Anemia/diagnóstico , Infecções por Coronavirus , Coronavirus/metabolismo , Ferro/metabolismo , Pandemias , Pneumonia Viral , Betacoronavirus , Biomarcadores/análise , Biomarcadores/sangue , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Eritropoetina , Ferritinas/sangue , Hemoglobinas/análise , Hemoglobinas/metabolismo , Hepcidinas/sangue , Hepcidinas/metabolismo , Humanos , Ferro/sangue , Pneumonia Viral/epidemiologia , Receptores da Transferrina/sangue , Transferrina/análise , Transferrina/metabolismo
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