Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21.260
Filtrar
1.
Front Cell Infect Microbiol ; 11: 598875, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33791232

RESUMEN

In the last year, the advent of the COVID-19 pandemic brought a new consideration for the multidisciplinary sciences. The unknown mechanisms of infection used by SARS-CoV-2 and the absence of effective antiviral pharmacological therapy, diagnosis methods, and vaccines evoked scientific efforts on the COVID-19 outcome. In general, COVID-19 clinical features are a result of local and systemic inflammatory processes that are enhanced by some preexistent comorbidities, such as diabetes, obesity, cardiovascular, and pulmonary diseases, and biological factors, like gender and age. However, the discrepancies in COVID-19 clinical signs observed among those patients lead to investigations about the critical factors that deeply influence disease severity and death. Herein, we present the viral infection mechanisms and its consequences after blocking the angiotensin-converting enzyme 2 (ACE2) axis in different tissues and the progression of inflammatory and immunological reactions, especially the influence of genetic features on those differential clinical responses. Furthermore, we discuss the role of genotype as an essential indicator of COVID-19 susceptibility, considering the expression profiles, polymorphisms, gene identification, and epigenetic modifications of viral entry factors and their recognition, as well as the infection effects on cell signaling molecule expression, which amplifies disease severity.


Asunto(s)
/metabolismo , Sistema Renina-Angiotensina/fisiología , Glicoproteína de la Espiga del Coronavirus/metabolismo , /genética , Antivirales/farmacología , Citocinas/sangre , Citocinas/inmunología , Humanos , Factores de Riesgo , Glicoproteína de la Espiga del Coronavirus/genética
2.
Sci Rep ; 11(1): 6428, 2021 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-33742062

RESUMEN

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


Asunto(s)
/etiología , Diabetes Mellitus Tipo 2/complicaciones , Activación de Macrófagos , Obesidad/complicaciones , Adulto , Anciano , Biomarcadores/sangre , /inmunología , Citocinas/sangre , Citocinas/inmunología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/inmunología , Femenino , Humanos , Inflamación/sangre , Inflamación/complicaciones , Inflamación/inmunología , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/inmunología , Proyectos Piloto , Estudios Prospectivos , Factores de Riesgo
3.
Medicine (Baltimore) ; 100(13): e24951, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33787581

RESUMEN

ABSTRACT: Hypertension is associated with chronic inflammation in the tissues and organs that are involved in the regulation of arterial pressure, such as kidneys and blood vessels. Periodontal disease affects systemic inflammatory markers, leading to endothelial dysfunction, atherosclerotic plaque instability, dyslipidaemia, and insulin resistance. These conditions can also cause an increase in the blood pressure. Nonsurgical periodontal therapies, such as scaling and root planning, can affect systemic markers of inflammation. We evaluated the effect of scaling and root planning on serum levels of inflammation biomarkers in hypertensive patients. The sample consisted of 19 hypertensive patients with Periodontitis. The patients underwent laboratory tests that included glycaemia, cholesterol, triglycerides and blood count. Blood pressure was measured before periodontal therapy, and the second blood pressure recording was obtained at the re-evaluation appointment. Quantification of peripheral blood cytokines was performed using the Milliplex Inflammation Human Cytokine kit (Interleukin 1-ß, Interleukin-4, Interleukin-6, Interleukin-8, Interleukin-10, Interleukin-12 P70, Interleukin-17A, vascular endothelial growth factor and tumor necrosis factor-alpha). All cytokine levels decreased from the initial examination to reassessment. Cytokines that reflected a statistically significant difference included Interleukin-1ß and endothelial vascular growth factor (P = .04 and P = .004). Hypertensive patients with periodontitis undergoing non-surgical periodontal treatment exhibited a decrease in proinflammatory cytokine levels. Non-surgical periodontal treatment decreases the levels of systemic proinflammatory cytokines in controlled hypertensive patients.


Asunto(s)
Raspado Dental , Hipertensión/complicaciones , Periodontitis/terapia , Aplanamiento de la Raíz , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Biomarcadores/sangre , Recuento de Células Sanguíneas , Glucemia/análisis , Presión Sanguínea , Colesterol/sangre , Citocinas/sangre , Femenino , Humanos , Hipertensión/sangre , Masculino , Persona de Mediana Edad , Periodontitis/sangre , Periodontitis/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Resultado del Tratamiento , Triglicéridos/sangre
4.
Sci Immunol ; 6(57)2021 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-33692097

RESUMEN

While it is now widely accepted that host inflammatory responses contribute to lung injury, the pathways that drive severity and distinguish coronavirus disease 2019 (COVID-19) from other viral lung diseases remain poorly characterized. We analyzed plasma samples from 471 hospitalized patients recruited through the prospective multicenter ISARIC4C study and 39 outpatients with mild disease, enabling extensive characterization of responses across a full spectrum of COVID-19 severity. Progressive elevation of levels of numerous inflammatory cytokines and chemokines (including IL-6, CXCL10, and GM-CSF) were associated with severity and accompanied by elevated markers of endothelial injury and thrombosis. Principal component and network analyses demonstrated central roles for IL-6 and GM-CSF in COVID-19 pathogenesis. Comparing these profiles to archived samples from patients with fatal influenza, IL-6 was equally elevated in both conditions whereas GM-CSF was prominent only in COVID-19. These findings further identify the key inflammatory, thrombotic, and vascular factors that characterize and distinguish severe and fatal COVID-19.


Asunto(s)
/sangre , Citocinas/sangre , Adulto , Anciano , Citocinas/inmunología , Femenino , Humanos , Inflamación/sangre , Inflamación/inmunología , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/sangre , Gripe Humana/inmunología , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad
5.
Undersea Hyperb Med ; 48(1): 1-12, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33648028

RESUMEN

The SARS-Cov-2 (COVID-19) pandemic remains a major worldwide public health issue. Initially, improved supportive and anti-inflammatory intervention, often employing known drugs or technologies, provided measurable improvement in management. We have recently seen advances in specific therapeutic interventions and in vaccines. Nevertheless, it will be months before most of the world's population can be vaccinated to achieve herd immunity. In the interim, hyperbaric oxygen (HBO2) treatment offers several potentially beneficial therapeutic effects. Three small published series, one with a propensity-score-matched control group, have demonstrated safety and initial efficacy. Additional anecdotal reports are consistent with these publications. HBO2 delivers oxygen in extreme conditions of hypoxemia and tissue hypoxia, even in the presence of lung pathology. It provides anti-inflammatory and anti-proinflammatory effects likely to ameliorate the overexuberant immune response common to COVID-19. Unlike steroids, it exerts these effects without immune suppression. One study suggests HBO2 may reduce the hypercoagulability seen in COVID patients. Also, hyperbaric oxygen offers a likely successful intervention to address the oxygen debt expected to arise from a prolonged period of hypoxemia and tissue hypoxia. To date, 11 studies designed to investigate the impact of HBO2 on patients infected with SARS-Cov-2 have been posted on clinicaltrials.gov. This paper describes the promising physiologic and biochemical effects of hyperbaric oxygen in COVID-19 and potentially in other disorders with similar pathologic mechanisms.


Asunto(s)
/terapia , Oxigenación Hiperbárica/métodos , /sangre , /inmunología , Hipoxia de la Célula , Síndrome de Liberación de Citoquinas/inmunología , Citocinas/sangre , Humanos , Hipoxia/terapia , Inflamación/terapia , Células Madre Mesenquimatosas , Oxígeno/envenenamiento , Consumo de Oxígeno , Trombofilia/etiología , Trombofilia/terapia
6.
Front Endocrinol (Lausanne) ; 12: 596518, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33776910

RESUMEN

Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04365634. Context: Diabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear. Objective: We aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients. Design and Methods: In this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups. Results: Compared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL-2R, IL-6, IL-8, IL-10, and TNF-α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF-α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8+ T cells and NK cells than survivors. Conclusion: The elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8+ T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM.


Asunto(s)
/inmunología , Diabetes Mellitus Tipo 2/inmunología , Adulto , Anciano , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , /complicaciones , China/epidemiología , Citocinas/análisis , Citocinas/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Humanos , Hiperglucemia/sangre , Hiperglucemia/complicaciones , Hiperglucemia/inmunología , Hiperglucemia/mortalidad , Sistema Inmunológico/metabolismo , Sistema Inmunológico/patología , Células Asesinas Naturales/patología , Recuento de Linfocitos , Linfopenia/sangre , Linfopenia/complicaciones , Linfopenia/inmunología , Linfopenia/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , /fisiología , Células TH1/patología , Células Th2/patología
7.
BMC Infect Dis ; 21(1): 250, 2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33691633

RESUMEN

BACKGROUND: Infants with bronchiolitis have an increased risk of developing recurrent wheezing and asthma. However, the risk factors for the development of recurrent wheezing after bronchiolitis remains controversial. Our study was to investigate risk factors of post-bronchiolitis recurrent wheezing. METHODS: Infants with bronchiolitis were enrolled from November 2016 through March 2017. Nasopharyngeal aspirates were obtained for detection of respiratory viruses which were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and direct immunofluorescent assay. Serum cytokines including TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α were measured by flow cytometry. Patients were followed up every 3 months for a duration of 2 years by telephone or at outpatient appointments. RESULTS: We enrolled 89 infants, of which 81 patients were successfully followed up. In total, 22.2% of patients experienced recurrent wheezing episodes. The proportion of patients with history of eczema, systemic glucocorticoid use and patients with moderate-to-severe disease were significantly higher in the recurrent wheezing group than the non-recurrent wheezing group (83.3% vs 52.4%; 66.7% vs 36.5%; 61.1% vs 33.3%, respectively, all P < 0.05); There were no significant differences between patients with and without recurrent wheezing episodes in the levels of TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α (P > 0.05). Logistic regression analysis showed that history of eczema was an independent risk factor for post-bronchiolitis recurrent wheezing (odds ratio [OR] = 5.622; 95% confidence interval [CI], 1.3-24.9; P = 0.023). CONCLUSION: The incidence of recurrent wheezing among infants after contracting bronchiolitis was 22.2% during a 2-year follow-up. History of eczema was the only independent risk factor identified and no correlation was found between the specific virus and disease severity in children with post-bronchiolitis recurrent wheezing.


Asunto(s)
Bronquiolitis/fisiopatología , Ruidos Respiratorios , Bronquiolitis/virología , China , Citocinas/sangre , Eccema/complicaciones , Femenino , Estudios de Seguimiento , Glucocorticoides/efectos adversos , Humanos , Incidencia , Lactante , Masculino , Recurrencia , Ruidos Respiratorios/etiología , Factores de Riesgo , Suero , Factor de Necrosis Tumoral alfa/sangre
8.
Medicine (Baltimore) ; 100(10): e25020, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33725883

RESUMEN

ABSTRACT: This study aimed to investigate the relationships between omentin-1, body composition and physical activity (PA) levels in older women.Eighty-one older women (age = 64 ±â€Š6years; body mass index = 24.2 ±â€Š3.2 kg/m2; body fat percentage = 36.1 ±â€Š5.7%) participated in this study. We divided the subjects into overweight/obesity and normal weight group. Body composition was measured by dual energy X-ray absorptiometry. Serum omentin-1 concentration was measured using enzyme linked immunosorbent assay. PA levels were obtained by using accelerometers. In addition, anthropometric and insulin resistance values were determined.Omentin-1 level in overweight/obesity group was significantly lower than in the normal weight group (P < .01). Analysis of all subjects showed that serum omentin-1 was negatively correlated with body weight, BMI (body mass index), waist circumference (WC), WHR (waist-to-hip ratio), percentage of body fat, total body fat mass (FM), fat-free mass (FFM) (r = -.571, -0.569, -0.546, -0.382, -0.394, -0.484, -0.524, all P < .01), respectively. We also found a negative correlation between moderate-to-vigorous physical activity (MVPA) and total body FM (r = -.233, P < .05). However, no significant correlation was found between omentin-1 and sedentary behavior and MVPA (both P > .05). Moreover, the relationship between omentin-1, body composition and PA was analyzed by using multiple linear stepwise regressions. The results showed that serum omentin-1 concentration was inversely correlated with total body FM (ß = -0.334, P = .004) in multiple linear stepwise regression analysis.We found that total body FM was inversely related to serum omentin-1 concentration and PA levels, but there was no correlation between omentin-1 and PA levels. These results showed that PA may participate in the regulation of body composition, which may be also affected by serum omentin-1. However, the mechanism by which PA affects body composition may not be through omentin-1 and was more likely through other metabolic pathways.


Asunto(s)
Composición Corporal/fisiología , Citocinas/sangre , Ejercicio Físico/fisiología , Lectinas/sangre , Absorciometría de Fotón , Acelerometría/estadística & datos numéricos , Anciano , Femenino , Proteínas Ligadas a GPI/sangre , Humanos , Persona de Mediana Edad
9.
Front Cell Infect Microbiol ; 11: 624483, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33718270

RESUMEN

The immune response type organized against viral infection is determinant in the prognosis of some infections. This work has aimed to study Th polarization in acute COVID-19 and its possible association with the outcome through an observational prospective study. Fifty-eight COVID-19 patients were recruited in the Medicine Department of the hospital "12 de Octubre," 55 patients remaining after losses to follow-up. Four groups were established according to maximum degree of disease progression. T-helper cell percentages and phenotypes, analyzed by flow cytometer, and serum cytokines levels, analyzed by Luminex, were evaluated when the microbiological diagnosis (acute phase) of the disease was obtained. Our study found a significant reduction of %Th1 and %Th17 cells with higher activated %Th2 cells in the COVID-19 patients compared with reference population. A higher percent of senescent Th2 cells was found in the patients who died than in those who survived. Senescent Th2 cell percentage was an independent risk factor for death (OR: 13.88) accompanied by the numbers of total lymphocytes (OR: 0.15) with an AUC of 0.879. COVID-19 patients showed a profile of pro-inflammatory serum cytokines compared to controls, with higher levels of IL-2, IL-6, IL-15, and IP-10. IL-10 and IL-13 were also elevated in patients compared to controls. Patients who did not survive presented significantly higher levels of IL-15 than those who recovered. No significant differences were observed according to disease progression groups. The study has shown that increased levels of IL-15 and a high Th2 response are associated with a fatal outcome of the disease.


Asunto(s)
/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Adulto , Anciano , /patología , Citocinas/sangre , Progresión de la Enfermedad , Femenino , Humanos , Inmunidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Células TH1/inmunología , Células Th17/inmunología , Células Th2/inmunología
10.
Indian J Ophthalmol ; 69(4): 985-986, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33727473

RESUMEN

A 32-year-old man with a clear and compact graft following a penetrating keratoplasty 6 years back, developed an episode of acute graft rejection, coinciding with the COVID-19 disease. Subsequent to the infection with the novel coronavirus, he developed symptoms of acute graft rejection concurrent with the development of respiratory distress and peak systemic symptoms. This was the phase of cytokine storm as evidenced by the raised inflammatory markers in his blood tests. Such a case of acute corneal graft rejection coinciding with SARS-CoV-2 infection has been reported only once in the literature and this unique association needs to be researched further.


Asunto(s)
/diagnóstico , Enfermedades de la Córnea/diagnóstico , Infecciones Virales del Ojo/diagnóstico , Rechazo de Injerto/diagnóstico , Queratoplastia Penetrante , Enfermedad Aguda , Adulto , /virología , Extracción de Catarata , Enfermedades de la Córnea/tratamiento farmacológico , Enfermedades de la Córnea/virología , Citocinas/sangre , Infecciones Virales del Ojo/tratamiento farmacológico , Infecciones Virales del Ojo/virología , Glucocorticoides/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/virología , Humanos , Incidencia , Mediadores de Inflamación/sangre , Implantación de Lentes Intraoculares , Masculino , Neumonía Viral/sangre , Prednisolona/uso terapéutico , Agudeza Visual
11.
Front Immunol ; 12: 629193, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33732251

RESUMEN

Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS), is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells activate and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with coronavirus 2019 (COVID-19) for a subgroup of patients. CRS is not unique to the SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, and H7N9). With a comprehensive literature search, we collected changing the cytokine levels from patients upon infection with the viral pathogens mentioned above. We analyzed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. Our curation indicates that the cytokine response induced by SARS-CoV-2 is different compared to other CRS-causing respiratory viruses, as SARS-CoV-2 does not always induce specific cytokines like other coronaviruses or influenza do, such as IL-2, IL-10, IL-4, or IL-5. Comparing the collated cytokine responses caused by the analyzed viruses highlights a SARS-CoV-2-specific dysregulation of the type-I interferon (IFN) response and its downstream cytokine signatures. The map of responses gathered in this study could help specialists identify interventions that alleviate CRS in different diseases and evaluate whether they could be used in the COVID-19 cases.


Asunto(s)
/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Virus del SRAS/inmunología , Síndrome Respiratorio Agudo Grave/inmunología , Índice de Severidad de la Enfermedad , /sangre , /virología , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/virología , Citocinas/sangre , Humanos , Inflamación/inmunología , Gripe Humana/sangre , Gripe Humana/virología , Síndrome Respiratorio Agudo Grave/sangre , Síndrome Respiratorio Agudo Grave/virología
12.
Front Immunol ; 12: 632890, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33732254

RESUMEN

Coronavirus disease-19 (COVID-19) in children is usually mild but some are susceptible to a Kawasaki disease (KD)-like multisystem inflammatory syndrome in children (MIS-C) in the convalescent stage, posing a need to differentiate the phenotype, susceptibility, autoimmunity, and immunotherapy between KD and MIS-C, particularly in the upcoming mass vaccination of COVID-19. Patients with MIS-C are prone to gastrointestinal symptoms, coagulopathy, and shock in addition to atypical KD syndrome with fever, mucocutaneous lesions, lymphadenopathy, and/or cardiovascular events. MIS-C manifests KD-like symptoms that alert physicians to early recognize and adopt the KD treatment regimen for patients with MIS-C. MIS-C linked to COVID-19 teaches us infection-associated autoimmune vasculitis and vice versa. Studies on genetic susceptibility have identified certain human leukocyte antigen (HLA) locus and toll-like receptor (TLR) associated with KD and/or COVID-19. Certain HLA subtypes, such as HLA-DRB1 and HLA-MICA A4 are associated with KD. HLA-B*46:01 is proposed to be the risk allele of severe COVID-19 infection, and blood group O type is a protective factor of COVID-19. The autoimmune vasculitis of KD, KD shock syndrome (KDSS), or MIS-C is mediated by a genetic variant of HLA, FcγR, and/or antibody-dependent enhancement (ADE) resulting in hyperinflammation with T helper 17 (Th17)/Treg imbalance with augmented Th17/Th1 mediators: interleukin-6 (IL-6), IL-10, inducible protein-10 (IP-10), Interferon (IFNγ), and IL-17A, and lower expression of Treg-signaling molecules, FoxP3, and transforming growth factor (TGF-ß). There are certain similarities and differences in phenotypes, susceptibility, and pathogenesis of KD, KDSS, and MIS-C, by which a physician can make early protection, prevention, and precision treatment of the diseases. The evolution of immunotherapies for the diseases has shown that intravenous immunoglobulin (IVIG) alone or combined with corticosteroids is the standard treatment for KD, KDSS, and MIS-C. However, a certain portion of patients who revealed a treatment resistance to IVIG or IVIG plus corticosteroids, posing a need to early identify the immunopathogenesis, to protect hosts with genetic susceptibility, and to combat Th17/Treg imbalance by anti-cytokine or pro-Treg for reversal of the hyperinflammation and IVIG resistance. Based on physiological and pathological immunity of the diseases under genetic susceptibility and host milieu conditions, a series of sequential regimens are provided to develop a so-called "Know thyself, enemy (pathogen), and ever-victorious" strategy for the prevention and immunotherapy of KD and/or MIS-C.


Asunto(s)
Autoinmunidad , /terapia , Predisposición Genética a la Enfermedad/genética , Inmunoterapia/métodos , Síndrome Mucocutáneo Linfonodular/inmunología , Síndrome Mucocutáneo Linfonodular/terapia , Fenotipo , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/terapia , Adolescente , Corticoesteroides/uso terapéutico , /virología , Niño , Preescolar , Citocinas/sangre , Femenino , Antígenos HLA/genética , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Lactante , Masculino , Síndrome Mucocutáneo Linfonodular/genética , Síndrome de Respuesta Inflamatoria Sistémica/genética , Síndrome de Respuesta Inflamatoria Sistémica/virología
13.
J Exp Med ; 218(5)2021 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-33646265

RESUMEN

The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 without symptoms could reveal nonpathological yet protective characteristics. We longitudinally studied SARS-CoV-2-specific T cells in a cohort of asymptomatic (n = 85) and symptomatic (n = 75) COVID-19 patients after seroconversion. We quantified T cells reactive to structural proteins (M, NP, and Spike) using ELISpot and cytokine secretion in whole blood. Frequencies of SARS-CoV-2-specific T cells were similar between asymptomatic and symptomatic individuals, but the former showed an increased IFN-γ and IL-2 production. This was associated with a proportional secretion of IL-10 and proinflammatory cytokines (IL-6, TNF-α, and IL-1ß) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2-infected individuals are not characterized by weak antiviral immunity; on the contrary, they mount a highly functional virus-specific cellular immune response.


Asunto(s)
Infecciones Asintomáticas , Citocinas/inmunología , Activación de Linfocitos , Linfocitos T/inmunología , Adulto , Citocinas/sangre , Humanos , Masculino , Persona de Mediana Edad , Linfocitos T/metabolismo
14.
Artículo en Inglés | MEDLINE | ID: mdl-33656139

RESUMEN

Currently, there are no biomarkers for Chikungunya fever (CHIK) in clinical practice that can accurately predict the severity or chronification of the disease. The aim of this study is to evaluate the existing literature on biomarkers related to the severity and chronification of CHIK. In this sense, a systematic review was conducted based on the PRISMA Statement guideline. Articles that described the association of biomarkers with the evolution of the disease (severity or chronification), published until August 20th 2019 were considered eligible. The search was carried out in the PubMed, Scopus, Virtual Health Library (VHL) and Science Direct databases. After searching the databases, 17 articles were added to the review, and after analyzing the articles, several biomarkers were associated with severity, such as increased levels of IL-6, IP-10, IL-1b, MIG, MCP-1, and reduced levels of RANTES and IL-8 or chronification, such as increased levels of IL-6, TNF-α, MCP-1, IL-12, INF-α, IL-13, INF-γ, GM-CSF, CRP, IL-1a, IL-15, Factor VII, IP-10, IL-10, IL-4, IL-1RA, IL-8, MIP-1α, MIP-1ß, ferritin, MIG, ESR, NO, malondialdehyde, and reduced levels of RANTES, ferritin, eotaxin, HGF, IL-27, IL-17A, IL-29, TGF-ß, IL-10, and thiols. IL-6, CRP and TNF-α were included in the meta-analysis to assess the relationship with chronification, although they did not reach statistical significance. It was concluded that several biomarkers showed a relationship with severity and chronification of CHIK; the search for these biomarkers can reveal prognostic factors and important therapeutic targets for the treatment of the disease.


Asunto(s)
Biomarcadores/sangre , Fiebre Chikungunya/diagnóstico , Citocinas/sangre , Fiebre Chikungunya/sangre , Humanos , Interleucinas/sangre , Índice de Severidad de la Enfermedad
15.
Int J Mol Med ; 47(4)2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33649807

RESUMEN

Excessive lung inflammation caused by endotoxins, including lipopolysaccharide (LPS), mediates the detrimental effects of acute lung injury (ALI), as evidenced by severe alveolar epithelial cell injury. CD40, a member of the tumor necrosis factor receptor superfamily, serves as a central activator in triggering and transducing a series of severe inflammatory events during the pathological processes of ALI. Ginkgolide C (GC) is an efficient and specific inhibitor of CD40. Therefore, the present study aimed to investigate whether GC alleviated LPS­induced ALI, as well as the potential underlying mechanisms. LPS­injured wild­type and CD40 gene conditional knockout mice, and primary cultured alveolar epithelial cells isolated from these mice served as in vivo and in vitro ALI models, respectively. In the present study, histopathological assessment, polymorphonuclear neutrophil (PMN) infiltration, lung injury score, myeloperoxidase activity, wet­to­dry (W/D) weight ratio and hydroxyproline (Hyp) activity were assessed to evaluate lung injury. In addition, immunohistochemistry was performed to evaluate intracellular adhesion molecule­1, vascular cell adhesion molecule­1 and inducible nitric oxide synthase expression levels, and TNF­α, IL­1ß, IL­6 ELISAs and western blotting were conducted to elucidate the signaling pathway. The results demonstrated that GC alleviated LPS­induced lung injury, as evidenced by improvements in ultrastructural characteristics and histopathological alterations of lung tissue, inhibited PMN infiltration, as well as reduced lung injury score, W/D weight ratio and hydroxyproline content. In LPS­injured alveolar epithelial cells, GC significantly reduced IκBα phosphorylation, IKKß activity and NF­κB p65 subunit translocation via downregulating CD40, leading to a significant decrease in downstream inflammatory cytokine levels and protein expression levels. In conclusion, the results of the present study demonstrated that GC displayed a protective effect against LPS­induced ALI via inhibition of the CD40/NF­κB signaling pathway; therefore, the present study suggested that the CD40/NF­κB signaling pathway might serve as a potential therapeutic target for ALI.


Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Antígenos CD40/antagonistas & inhibidores , Ginkgólidos/farmacología , Quinasa I-kappa B/metabolismo , Lactonas/farmacología , Factor de Transcripción ReIA/metabolismo , Lesión Pulmonar Aguda/patología , Animales , Antígenos CD40/genética , Antígenos CD40/metabolismo , Células Cultivadas , Citocinas/sangre , Hidroxiprolina/metabolismo , Inflamación/tratamiento farmacológico , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infiltración Neutrófila/efectos de los fármacos , Neutrófilos/inmunología , Peroxidasa/metabolismo , Transducción de Señal/efectos de los fármacos
16.
PLoS One ; 16(3): e0246681, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33661927

RESUMEN

Central nervous system and visual dysfunction is an unfortunate consequence of systemic hypoxia in the setting of cardiopulmonary disease, including infection with SARS-CoV-2, high-altitude cerebral edema and retinopathy and other conditions. Hypoxia-induced inflammatory signaling may lead to retinal inflammation, gliosis and visual disturbances. We investigated the consequences of systemic hypoxia using serial retinal optical coherence tomography and by assessing the earliest changes within 24h after hypoxia by measuring a proteomics panel of 39 cytokines, chemokines and growth factors in the plasma and retina, as well as using retinal histology. We induced severe systemic hypoxia in adult C57BL/6 mice using a hypoxia chamber (10% O2) for 1 week and rapidly assessed measurements within 1h compared with 18h after hypoxia. Optical coherence tomography revealed retinal tissue edema at 18h after hypoxia. Hierarchical clustering of plasma and retinal immune molecules revealed obvious segregation of the 1h posthypoxia group away from that of controls. One hour after hypoxia, there were 10 significantly increased molecules in plasma and 4 in retina. Interleukin-1ß and vascular endothelial growth factor were increased in both tissues. Concomitantly, there was significantly increased aquaporin-4, decreased Kir4.1, and increased gliosis in retinal histology. In summary, the immediate posthypoxic period is characterized by molecular changes consistent with systemic and retinal inflammation and retinal glial changes important in water transport, leading to tissue edema. This posthypoxic inflammation rapidly improves within 24h, consistent with the typically mild and transient visual disturbance in hypoxia, such as in high-altitude retinopathy. Given hypoxia increases risk of vision loss, more studies in at-risk patients, such as plasma immune profiling and in vivo retinal imaging, are needed in order to identify novel diagnostic or prognostic biomarkers of visual impairment in systemic hypoxia.


Asunto(s)
Hipoxia/complicaciones , Inflamación/etiología , Retina/patología , Animales , Sistema Nervioso Central/patología , Citocinas/análisis , Citocinas/sangre , Femenino , Hipoxia/sangre , Hipoxia/patología , Inflamación/sangre , Inflamación/patología , Péptidos y Proteínas de Señalización Intercelular/análisis , Péptidos y Proteínas de Señalización Intercelular/sangre , Masculino , Ratones Endogámicos C57BL
17.
Front Immunol ; 12: 581469, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33664741

RESUMEN

Background: Epidemiological factors, clinical characteristics, and risk factors for the mortality of COVID-19 patients have been studied, but the role of complementary systems, possible inflammatory and immune response mechanisms, and detailed clinical courses are uncertain and require further study. Methods: In this single center, retrospective case-control study, we included all COVID-19 inpatients transferred or admitted to Wuhan Tongji Hospital from January 3 to March 30 2020 who had definite clinical outcomes (cured or deceased) with complete laboratory and radiological results. Clinical data were extracted from the electronic medical records, and compared between the cured and deceased patients. ROC curves were used to evaluate the prognostic value of the clinical parameters, and multivariable logistic regression analysis was performed to explore the risk factors for mortality. The correlation between the variables was evaluated by Spearman correlation analysis. Results: 208 patients were included in this study, 182 patients were cured and discharged, 26 patients died from COVID-2019. Most patients had comorbidities, with hypertension as the most common chronic disease (80; 38%). The most common symptoms at onset were fever (149; 72%), cough (137; 66%), and dyspnea (113; 54%). Elevated leucocytes, neutrophils, inflammatory biomarkers (CRP, ferritin, IL6, IL8, procalcitonin), PT, D-dimer, myocardial enzymes, BUN, decreased lymphocyte and subsets (T cells, CD4 T cells, CD8 T cells, NK cells, T cells + B cells + NK cells), and immunological factors (C3, C4) indicated poor outcome. PT, C3, and T cells were confirmed as independent prognostic factors for mortality by logistic regression models. IL6 and CPR were positively correlated with neutrophils, but negatively with lymphocytes and lymphocyte subsets except B cells. IL8 and ferritin were negatively related to T cells and CD4 T cells. Positive associations existed between C3 and T cells, CD4 T cells, and CD8 T cells, whereas there was no significant correlation between C4 and lymphocyte subsets. PT was found positively correlated with IL6, IL8, and CRP. Reverse correlations were explored between C3, C4, and PT, CK-MB, total bilirubin. Conclusions: T cells, C3, and PT were identified as independent prognostic factors for mortality. Decreased C3 and C4, dysregulation of lymphocyte subsets and cytokines may lead to death after SARS-CoV-2 infection.


Asunto(s)
/epidemiología , Complemento C3/análisis , Citocinas/sangre , Subgrupos de Linfocitos T/inmunología , Anciano , Estudios de Casos y Controles , Comorbilidad , Femenino , Humanos , Hipertensión/complicaciones , Células Asesinas Naturales/inmunología , Recuento de Linfocitos , Linfopenia/patología , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
18.
Sci Adv ; 7(10)2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33674317

RESUMEN

Limited knowledge exists on immune markers associated with disease severity or recovery in patients with coronavirus disease 2019 (COVID-19). Here, we elucidated longitudinal evolution of SARS-CoV-2 antibody repertoire in patients with acute COVID-19. Differential kinetics was observed for immunoglobulin M (IgM)/IgG/IgA epitope diversity, antibody binding, and affinity maturation in "severe" versus "mild" COVID-19 patients. IgG profile demonstrated immunodominant antigenic sequences encompassing fusion peptide and receptor binding domain (RBD) in patients with mild COVID-19 who recovered early compared with "fatal" COVID-19 patients. In patients with severe COVID-19, high-titer IgA were observed, primarily against RBD, especially in patients who succumbed to SARS-CoV-2 infection. The patients with mild COVID-19 showed marked increase in antibody affinity maturation to prefusion SARS-CoV-2 spike that associated with faster recovery from COVID-19. This study revealed antibody markers associated with disease severity and resolution of clinical disease that could inform development and evaluation of effective immune-based countermeasures against COVID-19.


Asunto(s)
Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Biomarcadores/sangre , /patología , Índice de Severidad de la Enfermedad , Afinidad de Anticuerpos/inmunología , Formación de Anticuerpos/inmunología , /virología , Citocinas/sangre , Células HEK293 , Hospitalización , Humanos , Cambio de Clase de Inmunoglobulina , Cinética , Pruebas de Neutralización , Unión Proteica , Dominios Proteicos , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , Carga Viral
19.
Mediators Inflamm ; 2021: 6687412, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33679237

RESUMEN

Background: Novel coronavirus disease 2019 (COVID-19), an acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly progressed to a global pandemic. Currently, there are limited effective medications approved for this deadly disease. Objective: To investigate the potential predictors of COVID-19 mortality and risk factors for hyperinflammation in COVID-19. Methods: Retrospective analysis was carried out in 1,149 patients diagnosed with COVID-19 in Tongji Hospital, Wuhan, China, from 1/13/2020 to 3/15/2020. Results: We found significant differences in the rates of hyperuricemia (OR: 3.17, 95% CI: 2.13-4.70; p < 0.001) and hypoalbuminemia (OR: 5.68, 95% CI: 3.97-8.32; p < 0.001) between deceased and recovered patients. The percentages of hyperuricemia in deceased patients and recovered patients were 23.6% and 8.9%, respectively, which were higher than the reported age-standardized prevalence of 6.2% in Chinese population. Of note, the percentages of both IL-6 and uric acid levels in survived COVID-19 patients were above 90%, suggesting that they might be good specificity for indicators of mortality in COVID-19 patients. The serum level of uric acid (UA) was positively associated with ferritin, TNF-α, and IL-6 but not with anti-inflammatory cytokine IL-10. In addition, the levels of these proinflammatory cytokines in COVID-19 patients showed a trend of reduction after uric acid lowering therapy. Conclusions: Our results suggest that uric acid, the end product of purine metabolism, was increased in deceased patients with COVID-19. In addition, the serum level of uric acid was positively associated with inflammatory markers. Uric acid lowering therapy in COVID-19 patients with hyperuricemia may be beneficial.


Asunto(s)
/sangre , Pandemias , Ácido Úrico/sangre , Adulto , Anciano , Biomarcadores/sangre , China/epidemiología , Citocinas/sangre , Femenino , Humanos , Hiperuricemia/sangre , Hiperuricemia/complicaciones , Hiperuricemia/tratamiento farmacológico , Mediadores de Inflamación/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo
20.
Nat Commun ; 12(1): 1618, 2021 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-33712622

RESUMEN

Cytokine release syndrome (CRS) is a major cause of the multi-organ injury and fatal outcome induced by SARS-CoV-2 infection in severe COVID-19 patients. Metabolism can modulate the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism correlates with inflammatory responses and affects cytokine release in COVID-19 patients. Here we perform both metabolomics and cytokine/chemokine profiling on serum samples from healthy controls, mild and severe COVID-19 patients, and delineate their global metabolic and immune response landscape. Correlation analyses show tight associations between metabolites and proinflammatory cytokines/chemokines, such as IL-6, M-CSF, IL-1α, IL-1ß, and imply a potential regulatory crosstalk between arginine, tryptophan, purine metabolism and hyperinflammation. Importantly, we also demonstrate that targeting metabolism markedly modulates the proinflammatory cytokines release by peripheral blood mononuclear cells isolated from SARS-CoV-2-infected rhesus macaques ex vivo, hinting that exploiting metabolic alterations may be a potential strategy for treating fatal CRS in COVID-19.


Asunto(s)
/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/metabolismo , Citocinas/sangre , Metaboloma , Animales , Estudios de Casos y Controles , Estudios de Cohortes , Síndrome de Liberación de Citoquinas/terapia , Femenino , Estudios de Seguimiento , Humanos , Técnicas In Vitro , Mediadores de Inflamación/sangre , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Estudios Longitudinales , Macaca mulatta , Masculino , Redes y Vías Metabólicas , Pandemias
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...