Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.274
Filtrar
1.
RMD Open ; 7(1)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33790049

RESUMO

BACKGROUND: The CHIC study (COVID-19 High-intensity Immunosuppression in Cytokine storm syndrome) is a quasi-experimental treatment study exploring immunosuppressive treatment versus supportive treatment only in patients with COVID-19 with life-threatening hyperinflammation. Causal inference provides a means of investigating causality in non-randomised experiments. Here we report 14-day improvement as well as 30-day and 90-day mortality. PATIENTS AND METHODS: The first 86 patients (period 1) received optimal supportive care only; the second 86 patients (period 2) received methylprednisolone and (if necessary) tocilizumab, in addition to optimal supportive care. The main outcomes were 14-day clinical improvement and 30-day and 90-day survival. An 80% decline in C reactive protein (CRP) was recorded on or before day 13 (CRP >100 mg/L was an inclusion criterion). Non-linear mediation analysis was performed to decompose CRP-mediated effects of immunosuppression (defined as natural indirect effects) and non-CRP-mediated effects attributable to natural prognostic differences between periods (defined as natural direct effects). RESULTS: The natural direct (non-CRP-mediated) effects for period 2 versus period 1 showed an OR of 1.38 (38% better) for 14-day improvement and an OR of 1.16 (16% better) for 30-day and 90-day survival. The natural indirect (CRP-mediated) effects for period 2 showed an OR of 2.27 (127% better) for 14-day improvement, an OR of 1.60 (60% better) for 30-day survival and an OR of 1.49 (49% better) for 90-day survival. The number needed to treat was 5 for 14-day improvement, 9 for survival on day 30, and 10 for survival on day 90. CONCLUSION: Causal inference with non-linear mediation analysis further substantiates the claim that a brief but intensive treatment with immunosuppressants in patients with COVID-19 and systemic hyperinflammation adds to rapid recovery and saves lives. Causal inference is an alternative to conventional trial analysis, when randomised controlled trials are considered unethical, unfeasible or impracticable.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Proteína C-Reativa/imunologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Metilprednisolona/uso terapêutico , /imunologia , Causalidade , Síndrome da Liberação de Citocina/imunologia , Estudo Historicamente Controlado , Humanos , Inflamação/imunologia , Mortalidade , Taxa de Sobrevida , Resultado do Tratamento
2.
Trials ; 22(1): 246, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33810808

RESUMO

OBJECTIVES: This study is conducted to investigate efficacy of pomegranate juice on inflammatory biomarkers, C-reactive protein (CRP), interleukin 6(IL-6), erythrocyte sedimentation rate (ESR) and complete blood count (CBC) in hospitalized patients with mild to moderate coronavirus disease 2019 (COVID- 19). TRIAL DESIGN: This is a randomized, placebo-controlled, double-blind, parallel 2-arm (1:1 ratio) clinical trial. PARTICIPANTS: Patients with COVID-19 admitted to hospitals in Yasuj City, Kohgiluyeh and Boyer-Ahmad Province, Iran. INCLUSION CRITERIA: Informed consent Patients 18 years of age or older Diagnosis of COVID-19 based on real-time polymerase chain reaction (RT-PCR) test EXCLUSION CRITERIA: Pregnancy or lactation Immunoglobulin A (IgA) level <61 mg/dl Disseminated intravascular coagulation or any other types of coagulopathy Severe congestive heart failure Participation in any clinical trial within 30 days prior to enrollment in this RCT Other contraindications determined by the specialist. INTERVENTION AND COMPARATOR: Intervention: 500 ml pomegranate juice and standard of care hospital treatment for COVID-19 Comparator: matching placebo containing 500 ml of red water and standard of care hospital treatment for COVID-19 Both intervention and comparator to be taken twice a day, after lunch and dinner, for 14 days. CRITERIA FOR DISCONTINUING: Transfer of patients to intensive care unit (ICU) Death Unwillingness to continue participating in the study MAIN OUTCOMES: The main outcomes of this study are levels of inflammatory biomarkers, CRP, IL-6, ESR, and CBC after 14 days of treatment. RANDOMIZATION: Eligible patients will be randomly assigned into the intervention or control group in a 1:1 ratio. Randomization will be performed based on 8 permuted blocks with block sizes of 6 and they will be stratified according to sex and age categories. Randomization sequences will be prepared by the trial's pharmacist using computer-generated random numbers. BLINDING (MASKING): This study is a double-blind clinical trial (participant, researcher). The pomegranate juice and placebo juice are packaged in identical bottles, and the researcher and all the patients will be unaware of the study assignment until the end of the study. To ensure blinding, the randomization sequences will be kept in identical, opaque, sealed, and sequentially numbered envelopes. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The calculated total sample size is 48 patients, with 24 patients assigned into each group. TRIAL STATUS: The protocol is Version 1.0, on March 3, 2021. Recruitment started on February 28, 2021, and is anticipated to be completed by May 21, 2021. TRIAL REGISTRATION: The Name of registering trial Effects of Pomegranate Juice (Punica Granatum) on Inflammatory Biomarkers and CBC in Patients with COVID-19: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Iranian registry of clinical trials (IRCT) Registration Number: IRCT20150711023153N2 Date of Trial Registration February 28, 2021, retrospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials҆ website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
/terapia , Sucos de Frutas e Vegetais , Romã (Fruta) , Ensaios Clínicos Controlados Aleatórios como Assunto , Contagem de Células Sanguíneas , Sedimentação Sanguínea , Proteína C-Reativa/imunologia , /imunologia , Método Duplo-Cego , Hospitalização , Humanos , Interleucina-6/imunologia
3.
Aging (Albany NY) ; 13(5): 6289-6297, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33711813

RESUMO

OBJECTIVES: To retrospectively evaluate the clinical and immunological characteristics of patients who died of COVID-19 and to identify patients at high risk of death at an early stage and reduce their mortality. RESULTS: Total white blood cell count, neutrophil count and C-reactive protein were significantly higher in patients who died of COVID-19 than those who recovered from it (p < 0.05), but the total lymphocyte count, CD4 + T cells, CD8 + T cells, B cells and natural killer cells were significantly lower when compared in the same groups. Multiple logistic regression analysis showed that increased D-dimer, decreased CD4 + T cells and increased neutrophils were risk factors for mortality. Further multiple COX regression demonstrated that neutrophil ≥ 5.27 × 109/L increased the risk of death in COVID-19 patients after adjustment for age and gender. However, CD4 + T cells ≥ 260/µL appeared to reduce the risk of death. CONCLUSION: SARS-CoV-2 infection led to a significant decrease of lymphocytes, and decreased CD4 + T cell count was a risk factor for COVID-19 patients to develop severe disease and death. METHODS: This study included 190 hospitalized COVID-19 patients from January 30, 2020 to March 4, 2020 in Wuhan, China, of whom 85 died and 105 recovered. Two researchers independently collected the clinical and laboratory data from electronic medical records.


Assuntos
/sangue , Linfócitos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Proteína C-Reativa/análise , Proteína C-Reativa/imunologia , Linfócitos T CD4-Positivos/imunologia , /mortalidade , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/imunologia , Humanos , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , /isolamento & purificação
4.
Ann R Coll Surg Engl ; 103(3): e94-e97, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33645285

RESUMO

Behçet's disease is a rare disease characterised by recurrent oral ulcers, with systemic manifestations including genital ulcers, ocular disease, skin lesions, gastrointestinal disease, neurologic disease, vascular disease and arthritis. Most clinical manifestations of Behçet's disease are believed to be due to vasculitis. The heterogeneous clinical spectrum is influenced by sex, ethnicity and country of residence. Vascular manifestation in the form of isolated large brachial artery aneurysm is rare in children. Treatment involves aneurysmorrhaphy to avoid rupture or ischaemic sequelae in addition to lifelong medical management to control vasculitis.


Assuntos
Aneurisma/diagnóstico por imagem , Síndrome de Behçet/diagnóstico , Artéria Braquial/diagnóstico por imagem , Trombose/diagnóstico por imagem , Aneurisma/etiologia , Aneurisma/patologia , Aneurisma/cirurgia , Anticorpos Antinucleares/imunologia , Síndrome de Behçet/complicações , Síndrome de Behçet/imunologia , Síndrome de Behçet/patologia , Sedimentação Sanguínea , Artéria Braquial/patologia , Artéria Braquial/cirurgia , Proteína C-Reativa/imunologia , Pré-Escolar , Angiografia por Tomografia Computadorizada , Antígeno HLA-B51/imunologia , Humanos , Masculino , Veia Safena/transplante , Trombose/etiologia , Trombose/patologia , Trombose/cirurgia , Enxerto Vascular/métodos
5.
Medicine (Baltimore) ; 100(10): e24925, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725853

RESUMO

ABSTRACT: Ileocolonoscopy is currently recognized as the gold standard for evaluating mucosal healing in patients with Crohn disease (CD). However, the ideal noninvasive marker to assess mucosal healing instead of invasive ileocolonoscopy is not available. This study aimed to determine the correlations between the mucosal healing and serological optimizing markers in CD.This retrospective study consecutively included 62 CD patients with 137 hospitalizations between March 2014 and March 2020. On the basis of the Simple Endoscopic Score for Crohn's disease (SES-CD), the CD patients were divided into mucosal healing group (SES-CD ≤ 2) and nonmucosal healing group (SES-CD > 2). We collected the results of ileocolonoscopy examination and inflammatory markers and then serological optimizing markers, including C-reactive protein/albumin ratio (CRP/ALB), platelet/albumin ratio (PLT/ALB), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. The control group consisted of 50 healthy volunteers in the corresponding period.We found that CRP/ALB, PLT/ALB, NLR, and PLR were correlated with the mucosal healing of CD, and the correlation of CRP/ALB with the mucosal healing was the highest (r = -0.64). Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of CRP/ALB (0.87) was higher than NLR (0.69), PLR (0.72), and PLT/ALB (0.81). In the efficacy of assessing the mucosal healing in CD, the sensitivity of CRP/ALB, NLR, PLR, and PLT/ALB were 91.1%, 83.9%, 73.2%, and 73.2%, respectively, and the specificity was 76.5%, 46.9%, 64.2%, and 75.3%, respectively.CRP/ALB was the most appropriate marker to assess CD mucosal healing among the serological optimizing markers.


Assuntos
Proteína C-Reativa/análise , Doença de Crohn/diagnóstico , Mucosa Intestinal/imunologia , Albumina Sérica Humana/análise , Adulto , Biomarcadores/sangue , Proteína C-Reativa/imunologia , Colo/diagnóstico por imagem , Colo/imunologia , Colonoscopia , Doença de Crohn/sangue , Doença de Crohn/imunologia , Feminino , Humanos , Íleo/diagnóstico por imagem , Íleo/imunologia , Mucosa Intestinal/diagnóstico por imagem , Masculino , Estudos Retrospectivos , Albumina Sérica Humana/imunologia , Índice de Gravidade de Doença , Adulto Jovem
6.
Front Immunol ; 12: 630430, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679775

RESUMO

C-reactive protein (CRP) is the best-known acute phase protein. In humans, almost every type of inflammation is accompanied by an increase of CRP concentration. Until recently, the only known physiological function of CRP was the marking of cells to initiate their phagocytosis. This triggers the classical complement pathway up to C4, which helps to eliminate pathogens and dead cells. However, vital cells with reduced energy supply are also marked, which is useful in the case of a classical external wound because an important substrate for pathogens is disposed of, but is counterproductive at internal wounds (e.g., heart attack or stroke). This mechanism negatively affects clinical outcomes since it is established that CRP levels correlate with the prognosis of these indications. Here, we summarize what we can learn from a clinical study in which CRP was adsorbed from the bloodstream by CRP-apheresis. Recently, it was shown that CRP can have a direct effect on blood pressure in rabbits. This is interesting in regard to patients with high inflammation, as they often become tachycardic and need catecholamines. These two physiological effects of CRP apparently also occur in COVID-19. Parts of the lung become ischemic due to intra-alveolar edema and hemorrhage and in parallel CRP increases dramatically, hence it is assumed that CRP is also involved in this ischemic condition. It is meanwhile considered that most of the damage in COVID-19 is caused by the immune system. The high amounts of CRP could have an additional influence on blood pressure in severe COVID-19.


Assuntos
Proteína C-Reativa/imunologia , Infarto do Miocárdio/imunologia , Acidente Vascular Cerebral/imunologia , Animais , Morte Celular/imunologia , Hipóxia Celular/imunologia , Complemento C4/imunologia , Humanos , Coelhos
7.
PLoS One ; 16(2): e0247605, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33635872

RESUMO

Neutrophils participate in the early phase of the innate response to uncomplicated influenza A virus (IAV) infection but also are a major component in later stages of severe IAV or COVID 19 infection where neutrophil extracellular traps (NETs) and associated cell free histones are highly pro-inflammatory. It is likely that IAV interacts with histones during infection. We show that histone H4 binds to IAV and aggregates viral particles. In addition, histone H4 markedly potentiates IAV induced neutrophil respiratory burst responses. Prior studies have shown reactive oxidants to be detrimental during severe IAV infection. C reactive protein (CRP) and surfactant protein D (SP-D) rise during IAV infection. We now show that both of these innate immune proteins bind to histone H4 and significantly down regulate respiratory burst and other responses to histone H4. Isolated constructs composed only of the neck and carbohydrate recognition domain of SP-D also bind to histone H4 and partially limit neutrophil responses to it. These studies indicate that complexes formed of histones and IAV are a potent neutrophil activating stimulus. This finding could account for excess inflammation during IAV or other severe viral infections. The ability of CRP and SP-D to bind to histone H4 may be part of a protective response against excessive inflammation in vivo.


Assuntos
Proteína C-Reativa/imunologia , Histonas/imunologia , Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Neutrófilos/imunologia , Proteína D Associada a Surfactante Pulmonar/imunologia , Células Cultivadas , Humanos , Imunidade Inata , Inflamação/etiologia , Inflamação/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Influenza Humana/complicações
8.
BMJ Case Rep ; 14(1)2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495174

RESUMO

Constrictive pericarditis is a relatively uncommon form of cardiac failure and presents due to scarring and consequent loss of the normal elasticity of the pericardial sac. This results in abnormal/limited ventricular filling and symptoms of heart failure. The aetiology is varied, from infective causes to idiopathic causes, or can manifest after cardiothoracic surgery. This case involves a 46-year-old man presenting with acute group A beta haemolytic streptococcus infection, and over the subsequent 6 months develops constrictive pericarditis due to what is believed to be a rheumatic aetiology. The patient subsequently underwent pericardiectomy and had restoration of normal filling dynamics confirmed on follow-up echocardiography. This case provides a subject matter for the review of the features of constrictive pericarditis and its investigation and management. This case is that it highlights the fact that pericarditis is not a benign condition. Emerging evidence suggests that pericarditis is due to a failure in inflammatory regulatory mechanisms, and patients suffering this condition have a preponderance to 'autoinflammation'. Pericarditis should be recognised early and treated fully with anti-inflammatory agents.


Assuntos
Bacteriemia/diagnóstico , Pericardite Constritiva/diagnóstico , Cardiopatia Reumática/diagnóstico , Infecções Estreptocócicas/diagnóstico , Antibacterianos/uso terapêutico , Antiestreptolisina/imunologia , Bacteriemia/complicações , Bacteriemia/tratamento farmacológico , Hemocultura , Proteína C-Reativa/imunologia , Cateterismo Cardíaco , Ceftriaxona/uso terapêutico , Eletrocardiografia , Hospitalização , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pericardiectomia , Pericardite Constritiva/etiologia , Pericardite Constritiva/fisiopatologia , Pericardite Constritiva/cirurgia , Combinação Piperacilina e Tazobactam/uso terapêutico , Cardiopatia Reumática/etiologia , Cardiopatia Reumática/fisiopatologia , Cardiopatia Reumática/cirurgia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes , Pressão Ventricular
9.
Cells ; 9(12)2020 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-33322797

RESUMO

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to an adaptive immune response in the host and the formation of anti-SARS-CoV-2 specific antibodies. While IgG responses against SARS-CoV-2 have been characterized quite well, less is known about IgA. IgA2 activates immune cells and induces inflammation and neutrophil extracellular trap (NET) formation which may contribute to organ injury and fatal outcome in SARS-CoV-2-infected patients. SARS-CoV-2 spike protein specific antibody levels were measured in plasma samples of 15 noninfected controls and 82 SARS-CoV-2-infected patients with no or mild symptoms, moderate symptoms (hospitalization) or severe disease (intensive care unit, ICU). Antibody levels were compared to levels of C-reactive protein (CRP) and circulating extracellular DNA (ecDNA) as markers for general inflammation and NET formation, respectively. While levels of SARS-CoV-2-specific IgG were similar in all patient groups, IgA2 antibodies were restricted to severe disease and showed the strongest discrimination between nonfatal and fatal outcome in patients with severe SARS-CoV-2 infection. While anti-SARS-CoV-2 IgG and IgA2 levels correlated with CRP levels in severely diseased patients, only anti-SARS-CoV-2 IgA2 correlated with ecDNA. These data suggest that the formation of anti-SARS-CoV-2 IgA2 during SARS-CoV-2 infection is a marker for more severe disease related to NET formation and poor outcome.


Assuntos
Anticorpos Antivirais/sangue , Armadilhas Extracelulares/imunologia , Imunoglobulina A/sangue , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/imunologia , Estudos de Casos e Controles , Ácidos Nucleicos Livres/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
10.
J Med Case Rep ; 14(1): 246, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33339534

RESUMO

BACKGROUND: In December 2019, a new coronavirus (named severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) spread from China, causing a pandemic in a very short time. The main clinical presentation of SARS-CoV-2 infection (COVID-19, coronavirus disease-2019) is pneumonia, but several cardiovascular complications may also occur (e.g., acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure and cardiogenic shock). Direct or indirect mechanisms induced by SARS-CoV-2 could be implicated in the pathogenesis of these events. CASE PRESENTATION: We report herein the third case of COVID-19 autoimmune haemolytic anaemia (AIHA) reported so far, which occurredwithout any other possible explanations in a Caucasian patient. The patient also suffered from ST-elevation myocardial injury. CONCLUSIONS: Both complications occurred quite late after COVID-19 diagnosis and were probably precipitated by systemic inflammation, as indicated by a significant delayed increase in inflammatory markers, including interleukin-6 (IL-6).


Assuntos
Anemia Hemolítica Autoimune/sangue , Infecções Assintomáticas , Proteína C-Reativa/imunologia , Interleucina-6/imunologia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Idoso de 80 Anos ou mais , Anemia Hemolítica Autoimune/tratamento farmacológico , Anemia Hemolítica Autoimune/etiologia , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , /tratamento farmacológico , Teste de Coombs , Eletrocardiografia , Inibidores Enzimáticos/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Prednisolona/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia
11.
Front Immunol ; 11: 574593, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072117

RESUMO

Familial Mediterranean Fever (FMF) and COVID-19 show a remarkable overlap of clinical symptoms and similar laboratory findings. Both are characterized by fever, abdominal/chest pain, elevation of C-reactive protein, and leukocytosis. In addition, colchicine and IL-1 inhibitors treatments that are effective in controlling inflammation in FMF patients have recently been proposed for off-label use in COVID-19 patients. Thus, FMF may resemble a milder recapitulation of the cytokine storm that is a hallmark of COVID-19 patients progressing to severe disease. We analyzed the sequence of the MEFV-encoded Pyrin protein - whose mutations cause FMF- in mammals, bats and pangolin. Intriguingly, although Pyrin is extremely conserved in species that are considered either a reservoir or intermediate hosts for SARS-CoV-2, some of the most common FMF-causing variants in humans are present as wildtype residues in these species. We propose that in humans, Pyrin may have evolved to fight highly pathogenic infections.


Assuntos
Betacoronavirus , Colchicina/uso terapêutico , Infecções por Coronavirus , Febre Familiar do Mediterrâneo , Mutação , Pandemias , Pneumonia Viral , Pirina , Animais , Betacoronavirus/genética , Betacoronavirus/imunologia , Proteína C-Reativa/genética , Proteína C-Reativa/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/genética , Febre Familiar do Mediterrâneo/imunologia , Humanos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Pirina/genética , Pirina/imunologia
12.
J Nanobiotechnology ; 18(1): 130, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912236

RESUMO

Fast point-of-care (POC) diagnostics represent an unmet medical need and include applications such as lateral flow assays (LFAs) for the diagnosis of sepsis and consequences of cytokine storms and for the treatment of COVID-19 and other systemic, inflammatory events not caused by infection. Because of the complex pathophysiology of sepsis, multiple biomarkers must be analyzed to compensate for the low sensitivity and specificity of single biomarker targets. Conventional LFAs, such as gold nanoparticle dyed assays, are limited to approximately five targets-the maximum number of test lines on an assay. To increase the information obtainable from each test line, we combined green and red emitting quantum dots (QDs) as labels for C-reactive protein (CRP) and interleukin-6 (IL-6) antibodies in an optical duplex immunoassay. CdSe-QDs with sharp and tunable emission bands were used to simultaneously quantify CRP and IL-6 in a single test line, by using a single UV-light source and two suitable emission filters for readout through a widely available BioImager device. For image and data processing, a customized software tool, the MultiFlow-Shiny app was used to accelerate and simplify the readout process. The app software provides advanced tools for image processing, including assisted extraction of line intensities, advanced background correction and an easy workflow for creation and handling of experimental data in quantitative LFAs. The results generated with our MultiFlow-Shiny app were superior to those generated with the popular software ImageJ and resulted in lower detection limits. Our assay is applicable for detecting clinically relevant ranges of both target proteins and therefore may serve as a powerful tool for POC diagnosis of inflammation and infectious events.


Assuntos
Biomarcadores/análise , Proteína C-Reativa/análise , Imunoensaio/métodos , Interleucina-6/análise , Pontos Quânticos/química , Sepse/diagnóstico , Anticorpos/imunologia , Betacoronavirus/isolamento & purificação , Proteína C-Reativa/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Humanos , Interleucina-6/imunologia , Limite de Detecção , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Sistemas Automatizados de Assistência Junto ao Leito , Sepse/metabolismo , Software , Raios Ultravioleta
14.
Eur J Immunol ; 50(9): 1283-1294, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32910469

RESUMO

Studies on the interactions between SARS-CoV-2 and humoral immunity are fundamental to elaborate effective therapies including vaccines. We used polychromatic flow cytometry, coupled with unsupervised data analysis and principal component analysis (PCA), to interrogate B cells in untreated patients with COVID-19 pneumonia. COVID-19 patients displayed normal plasma levels of the main immunoglobulin classes, of antibodies against common antigens or against antigens present in common vaccines. However, we found a decreased number of total and naïve B cells, along with decreased percentages and numbers of memory switched and unswitched B cells. On the contrary, IgM+ and IgM- plasmablasts were significantly increased. In vitro cell activation revealed that B lymphocytes showed a normal proliferation index and number of dividing cells per cycle. PCA indicated that B-cell number, naive and memory B cells but not plasmablasts clustered with patients who were discharged, while plasma IgM level, C-reactive protein, D-dimer, and SOFA score with those who died. In patients with pneumonia, the derangement of the B-cell compartment could be one of the causes of the immunological failure to control SARS-Cov2, have a relevant influence on several pathways, organs and systems, and must be considered to develop vaccine strategies.


Assuntos
Anticorpos Antivirais/sangue , Linfócitos B/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Isotipos de Imunoglobulinas/sangue , Pulmão/imunologia , Pneumonia Viral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/classificação , Linfócitos B/virologia , Betacoronavirus/imunologia , Proteína C-Reativa/imunologia , Estudos de Casos e Controles , Proliferação de Células , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Estudos Transversais , Citocinas/genética , Citocinas/imunologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/imunologia , Humanos , Imunidade Humoral , Memória Imunológica , Pulmão/patologia , Pulmão/virologia , Ativação Linfocitária , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Cultura Primária de Células , Índice de Gravidade de Doença , Análise de Sobrevida
15.
Pediatr Pulmonol ; 55(12): 3587-3594, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32991038

RESUMO

BACKGROUND: The novel coronavirus disease (Covid-19) can progress with mild to moderate or self-limiting clinical findings in children. The aim of this study was to investigate the disease features of Covid-19 in Turkish children. METHODS: Children diagnosed by the method of real-time reverse transcription-polymerase chain reaction for Covid-19 at the Dicle University Department of Pediatric, between April and June 2020, were evaluated. Hospital records were investigated retrospectively. RESULTS: One hundred and five patients children with the mean age of 108.64 ± 65.61 months were enrolled in this study. The most common cause of transmission in pediatric patients was in contact with a family member diagnosed with COVID-19 (n = 91, 86.7%). The most common admission complaints were dry cough (n = 17, 16.2%), fever (n = 16, 15.2%), lassitude and fatigue (n = 14, 13.3%) respectively. More than 95% of all children with Covid-19 were asymptomatic, mild, or moderate cases. CRP was identified only independent factor associated with long duration of hospitalization. CONCLUSION: The results of this study show the effect of Covid-19 on Turkish children. A clear understanding of the local epidemiology of corona virus infections and identification of risk factors are critical for the successful implementation of the prevention and control program.


Assuntos
Infecções Assintomáticas , Proteína C-Reativa/imunologia , Infecções por Coronavirus/fisiopatologia , Tempo de Internação/estatística & dados numéricos , Pneumonia Viral/fisiopatologia , Adolescente , Betacoronavirus , Criança , Pré-Escolar , Coronavirus , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/imunologia , Tosse/fisiopatologia , Fadiga/fisiopatologia , Feminino , Febre/fisiopatologia , Hospitalização , Humanos , Lactente , Pulmão/diagnóstico por imagem , Masculino , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/imunologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Turquia
17.
Brain Behav Immun ; 89: 594-600, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32738287

RESUMO

Infection-triggered perturbation of the immune system could induce psychopathology, and psychiatric sequelae were observed after previous coronavirus outbreaks. The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. We investigated the psychopathological impact of COVID-19 in survivors, also considering the effect of clinical and inflammatory predictors. We screened for psychiatric symptoms 402 adults surviving COVID-19 (265 male, mean age 58), at one month follow-up after hospital treatment. A clinical interview and a battery of self-report questionnaires were used to investigate post-traumatic stress disorder (PTSD), depression, anxiety, insomnia, and obsessive-compulsive (OC) symptomatology. We collected sociodemographic information, clinical data, baseline inflammatory markers and follow-up oxygen saturation levels. A significant proportion of patients self-rated in the psychopathological range: 28% for PTSD, 31% for depression, 42% for anxiety, 20% for OC symptoms, and 40% for insomnia. Overall, 56% scored in the pathological range in at least one clinical dimension. Despite significantly lower levels of baseline inflammatory markers, females suffered more for both anxiety and depression. Patients with a positive previous psychiatric diagnosis showed increased scores on most psychopathological measures, with similar baseline inflammation. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, positively associated with scores of depression and anxiety at follow-up. PTSD, major depression, and anxiety, are all high-burden non-communicable conditions associated with years of life lived with disability. Considering the alarming impact of COVID-19 infection on mental health, the current insights on inflammation in psychiatry, and the present observation of worse inflammation leading to worse depression, we recommend to assess psychopathology of COVID-19 survivors and to deepen research on inflammatory biomarkers, in order to diagnose and treat emergent psychiatric conditions.


Assuntos
Transtornos de Ansiedade/epidemiologia , Infecções por Coronavirus/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Pneumonia Viral/epidemiologia , Sobreviventes/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/epidemiologia , Ansiedade/imunologia , Ansiedade/psicologia , Transtornos de Ansiedade/imunologia , Transtornos de Ansiedade/psicologia , Betacoronavirus , Proteína C-Reativa/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/psicologia , Depressão/epidemiologia , Depressão/imunologia , Depressão/psicologia , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/imunologia , Transtorno Depressivo/psicologia , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/psicologia , Serviço Hospitalar de Emergência , Feminino , Humanos , Inflamação , Itália/epidemiologia , Tempo de Internação/estatística & dados numéricos , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/imunologia , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Monócitos , Neutrófilos , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/imunologia , Transtorno Obsessivo-Compulsivo/psicologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/psicologia , Índice de Gravidade de Doença , Fatores Sexuais , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/imunologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia
18.
Ann Rheum Dis ; 79(10): 1277-1285, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32620597

RESUMO

OBJECTIVES: To assess the safety and efficacy of interleukin (IL)-6 blockade with sarilumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation. METHODS: We conducted an open-label study of sarilumab in severe COVID-19 pneumonia (PaO2/FiO2 <300 mm Hg) with hyperinflammation (elevated inflammatory markers and serum IL-6 levels). Sarilumab 400 mg was administered intravenously in addition to standard of care and results were compared with contemporary matched patients treated with standard of care alone. Clinical improvement, mortality, safety and predictors of response were assessed at 28 days. RESULTS: Twenty-eight patients were treated with sarilumab and 28 contemporary patients receiving standard of care alone were used as controls. At day 28 of follow-up, 61% of patients treated with sarilumab experienced clinical improvement and 7% died. These findings were not significantly different from the comparison group (clinical improvement 64%, mortality 18%; p=NS). Baseline PaO2/FiO2 ratio >100 mm Hg and lung consolidation <17% at CT scan predicted clinical improvement in patients treated with sarilumab. Median time to clinical improvement in patients with lung consolidation <17% was shorter after sarilumab (10 days) than after standard treatment (24 days; p=0.01). The rate of infection and pulmonary thrombosis was similar between the two groups. CONCLUSIONS: At day 28, overall clinical improvement and mortality in patients with severe COVID-19 were not significantly different between sarilumab and standard of care. Sarilumab was associated with faster recovery in a subset of patients showing minor lung consolidation at baseline.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Proteína C-Reativa/imunologia , Infecções por Coronavirus/tratamento farmacológico , Inflamação/imunologia , Interleucina-6/imunologia , Pneumonia Viral/tratamento farmacológico , Administração Intravenosa , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Bacteriemia/epidemiologia , Betacoronavirus , Estudos de Coortes , Coinfecção/epidemiologia , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Combinação de Medicamentos , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Itália , Lopinavir/uso terapêutico , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ventilação não Invasiva , Oxigenoterapia , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Modelos de Riscos Proporcionais , Receptores de Interleucina-6/antagonistas & inibidores , Ritonavir/uso terapêutico , Índice de Gravidade de Doença , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
JAMA Netw Open ; 3(6): e2010895, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32492165

RESUMO

Importance: The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce. Objective: To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients. Design, Setting, and Participants: This single-center case series included 157 pediatric patients admitted to Wuhan Children's Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020. Exposures: Documented SARS-CoV-2 infection. Main Outcomes and Measures: Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020. Results: Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/µL [1680/µL-3510/µL] vs 3120/µL [2040/µL-4170/µL]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, -0.3579; AST: r, -0.5280; CK-MB activity: r, -0.4786; LDH: r, -0.4984; and neutrophil to lymphocyte ratio, ALT: r, -0.1893; AST: r, -0.3912; CK-MB activity: r, -0.3428; LDH: r, -0.3234), while counts of lymphocytes, CD4+ T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4+ T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794). Conclusions and Relevance: In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4+ T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.


Assuntos
Infecções por Coronavirus/imunologia , Citocinas/imunologia , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Distribuição por Idade , Alanina Transaminase/metabolismo , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Aspartato Aminotransferases/metabolismo , Linfócitos B/imunologia , Proteína C-Reativa/imunologia , Linfócitos T CD4-Positivos/imunologia , Criança , Pré-Escolar , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/terapia , Creatina Quinase Forma MB/metabolismo , Estado Terminal , Feminino , Hospitais Pediátricos , Humanos , Lactente , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-2/imunologia , Interleucina-4/imunologia , Interleucina-6/imunologia , Células Matadoras Naturais/imunologia , L-Lactato Desidrogenase/metabolismo , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Pneumonia Viral/terapia , Índice de Gravidade de Doença , Distribuição por Sexo , Fator de Necrose Tumoral alfa/imunologia
20.
J Allergy Clin Immunol Pract ; 8(8): 2585-2591.e1, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32574840

RESUMO

BACKGROUND: The clinical management of coronavirus disease 2019 (COVID-19) is dependent on understanding the underlying factors that contribute to the disease severity. In the absence of effective antiviral therapies, other host immunomodulatory therapies such as targeting inflammatory response are currently being used without clear evidence of their effectiveness. Because inflammation is an essential component of host antiviral mechanisms, therapies targeting inflammation may adversely affect viral clearance and disease outcome. OBJECTIVE: To understand whether the persistent presence of the virus is a key determinant in the disease severity during COVID-19 and to determine whether the viral reactivation in some patients is associated with infectious viral particles. METHODS: The data for patients were available including the onset of the disease, duration of viral persistence, measurements of inflammatory markers such as IL-6 and C-reactive protein, chest imaging, disease symptoms, and their durations among others. Follow-up tests were performed to determine whether the viral negative status persists after their recovery. RESULTS: Our data show that patients with persistent viral presence (>16 days) have more severe disease outcomes including extensive lung involvement and requirement of respiratory support. Two patients who died of COVID-19 were virus-positive at the time of their death. Four patients demonstrated virus-positive status on the follow-up tests, and these patient samples were sent to viral culture facility where virus culture could not be established. CONCLUSIONS: These data suggest that viral persistence is the key determining factor of the disease severity. Therapies that may impair the viral clearance may impair the host recovery from COVID-19.


Assuntos
Infecções por Coronavirus/fisiopatologia , Inflamação/fisiopatologia , Pneumonia Viral/fisiopatologia , Adolescente , Adulto , Idoso , Betacoronavirus , Proteína C-Reativa/imunologia , Criança , Pré-Escolar , Comorbidade , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Lactente , Inflamação/epidemiologia , Inflamação/imunologia , Mediadores da Inflamação/imunologia , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Respiração Artificial , Índice de Gravidade de Doença , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...