Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.413
Filtrar
1.
Trials ; 22(1): 674, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600562

RESUMO

BACKGROUND: Moderate/severe cases of COVID-19 present a dysregulated immune system with T cell lymphopenia and a hyper-inflammatory state. This is a study protocol of an open-label, multi-center, double-arm, randomized, dose-finding phase I/II clinical trial to evaluate the safety, tolerability, alloreactivity, and efficacy of the administration of allogeneic memory T cells and natural killer (NK) cells in COVID-19 patients with lymphopenia and/or pneumonia. The aim of the study is to determine the safety and the efficacy of the recommended phase 2 dose (RP2D) of this treatment for patients with moderate/severe COVID-19. METHODS: In the phase I trial, 18 patients with COVID-19-related pneumonia and/or lymphopenia with no oxygen requirement or with an oxygen need of ≤ 2.5 liters per minute (lpm) in nasal cannula will be assigned to two arms, based on the biology of the donor and the patient. Treatment of arm A consists of the administration of escalating doses of memory T cells, plus standard of care (SoC). Treatment of arm B consists of the administration of escalating doses of NK cells, plus SoC. In the phase II trial, a total of 182 patients with COVID-19-related pneumonia and/or lymphopenia requiring or not oxygen supplementation but without mechanical ventilation will be allocated to arm A or B, considering HLA typing. Within each arm, they will be randomized in a 1:1 ratio. In arm A, patients will receive SoC or RP2D for memory T cells plus the SoC. In arm B, patients will receive SoC or RP2D for NK cells plus the SoC. DISCUSSION: We hypothesized that SARS-CoV-2-specific memory T-lymphocytes obtained from convalescent donors recovered from COVID-19 can be used as a passive cell immunotherapy to treat pneumonia and lymphopenia in moderate/severe patients. The lymphopenia induced by COVID-19 constitutes a therapeutic window that may facilitate donor engraftment and viral protection until recovery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04578210 . First Posted : October 8, 2020.


Assuntos
COVID-19 , Linfopenia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Humanos , Memória Imunológica , Células Matadoras Naturais , Linfopenia/diagnóstico , Linfopenia/terapia , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Linfócitos T , Resultado do Tratamento
2.
Immunol Allergy Clin North Am ; 41(4): 543-553, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34602227

RESUMO

The T-cell receptor excision circle (TREC) assay is an effective screening tool for severe combined immunodeficiency (SCID). The TREC assay was designed to detect typical SCID and leaky SCID, but any condition causing low naïve T-cell counts will also be detected. Newborn screening for SCID using the TREC assay has proven itself to be highly sensitive and cost-efficient. This review covers the history of SCID newborn screening, elaborates on the SCID subtypes and TREC assay limitations, and discusses diagnostic and management considerations for infants with a positive screen.


Assuntos
Linfopenia , Imunodeficiência Combinada Severa , Humanos , Recém-Nascido , Triagem Neonatal , Receptores de Antígenos de Linfócitos T/genética , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/terapia
3.
Front Immunol ; 12: 715023, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659204

RESUMO

Emerging evidence has unveiled the secondary infection as one of the mortal causes of post-SARS-CoV-2 infection, but the factors related to secondary bacterial or fungi infection remains largely unexplored. We here systematically investigated the factors that might contribute to secondary infection. By clinical examination index analysis of patients, combined with the integrative analysis with RNA-seq analysis in the peripheral blood mononuclear cell isolated shortly from initial infection, this study showed that the antibiotic catabolic process and myeloid cell homeostasis were activated while the T-cell response were relatively repressed in those with the risk of secondary infection. Further monitoring analysis of immune cell and liver injury analysis showed that the risk of secondary infection was accompanied by severe lymphocytopenia at the intermediate and late stages and liver injury at the early stages of SARS-CoV-2. Moreover, the metagenomics analysis of bronchoalveolar lavage fluid and the microbial culture analysis, to some extent, showed that the severe pneumonia-related bacteria have already existed in the initial infection.


Assuntos
Infecções Bacterianas/epidemiologia , COVID-19/patologia , Coinfecção/epidemiologia , Coinfecção/mortalidade , Micoses/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/mortalidade , Líquido da Lavagem Broncoalveolar/microbiologia , Contagem de Linfócito CD4 , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Fígado/lesões , Fígado/virologia , Linfopenia/imunologia , Masculino , Pessoa de Meia-Idade , Micoses/mortalidade , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/imunologia , Linfócitos T/imunologia
4.
Front Immunol ; 12: 735922, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671353

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. COVID-19 is considered an airway/multi-systemic disease, and demise has been associated with an uncontrolled immune response and a cytokine storm in response to the virus. However, the lung pathology, immune response, and tissue damage associated with COVID-19 demise are poorly described and understood due to safety concerns. Using post-mortem lung tissues from uninfected and COVID-19 deadly cases as well as an unbiased combined analysis of histology, multi-viral and host markers staining, correlative microscopy, confocal, and image analysis, we identified three distinct phenotypes of COVID-19-induced lung damage. First, a COVID-19-induced hemorrhage characterized by minimal immune infiltration and large thrombus; Second, a COVID-19-induced immune infiltration with excessive immune cell infiltration but no hemorrhagic events. The third phenotype correspond to the combination of the two previous ones. We observed the loss of alveolar wall integrity, detachment of lung tissue pieces, fibroblast proliferation, and extensive fibrosis in all three phenotypes. Although lung tissues studied were from lethal COVID-19, a strong immune response was observed in all cases analyzed with significant B cell and poor T cell infiltrations, suggesting an exhausted or compromised immune cellular response in these patients. Overall, our data show that SARS-CoV-2-induced lung damage is highly heterogeneous. These individual differences need to be considered to understand the acute and long-term COVID-19 consequences.


Assuntos
COVID-19/mortalidade , COVID-19/patologia , Lesão Pulmonar/patologia , Alvéolos Pulmonares/patologia , Fibrose Pulmonar/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Linfócitos T CD8-Positivos/imunologia , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/patologia , Células Epiteliais/patologia , Feminino , Hemorragia/patologia , Humanos , Inflamação/patologia , Pulmão/patologia , Lesão Pulmonar/virologia , Linfopenia/patologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/patologia , Neutrófilos/imunologia , SARS-CoV-2 , Trombose/patologia
5.
J Infect Dev Ctries ; 15(9): 1263-1272, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34669594

RESUMO

INTRODUCTION: Factors such as comorbidity, age and gender distribution are mostly related to hospitalization, numbers requiring intensive care and case fatality rate. In this review, the fatality rate of coronavirus disease 2019 (COVID-19) in different population health background according to comorbidity, age, gender distribution, and laboratory prognosis for COVID-19. METHODOLOGY: The current review was based on the data from copious studies that had homogeneity in relation to the review's objectives. It included the newest studies from December 2019 to September 2020. The epidemiological reasons for the high morbidity and mortality rates among COVID-19 patients were analyzed in different countries. RESULTS: The highest comorbidity prevalence of COVID-19 was recorded in the United States of America (USA) (93.9%) and Italy (68%). Among population health background factors, comorbidity was the most common cause of COVID-19 fatality in the USA. The mean age of the most COVID-19 fatalities was more than 60 years old. Most of the studies show that 60% of COVID-19 patients were male. The fatality rates for the age group of 80-89 years-old in Korea, China, and Italy were 8.7 %, 14.7 %, and 18.8 % respectively. Lymphocytopenia has been observed in 91% of COVID-19 death cases. C - reactive protein had increased in 40-60% of COVID-19 patients. CONCLUSIONS: Many factors contribute to COVID-19 severity and fatality rates. Comorbidity, age, and gender were the main reasons for the Case Fatality Rate. This review recommends to follow preventive measures for overcoming the challenges faced during this emerging pandemic disease.


Assuntos
Fatores Etários , COVID-19/mortalidade , Comorbidade , Fatores Sexuais , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa , China/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Linfopenia , Masculino , Pessoa de Meia-Idade , Pandemias , República da Coreia/epidemiologia , Estados Unidos/epidemiologia
6.
JCO Clin Cancer Inform ; 5: 1044-1053, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34665662

RESUMO

PURPOSE: Radiotherapy (RT)-induced lymphopenia (RIL) is commonly associated with adverse clinical outcomes in patients with cancer. Using machine learning techniques, a retrospective study was conducted for patients with esophageal cancer treated with proton and photon therapies to characterize the principal pretreatment clinical and radiation dosimetric risk factors of grade 4 RIL (G4RIL) as well as to establish G4RIL risk profiles. METHODS: A single-institution retrospective data of 746 patients with esophageal cancer treated with photons (n = 500) and protons (n = 246) was reviewed. The primary end point of our study was G4RIL. Clustering techniques were applied to identify patient subpopulations with similar pretreatment clinical and radiation dosimetric characteristics. XGBoost was built on a training set (n = 499) to predict G4RIL risks. Predictive performance was assessed on the remaining n = 247 patients. SHapley Additive exPlanations were used to rank the importance of individual predictors. Counterfactual analyses compared patients' risk profiles assuming that they had switched modalities. RESULTS: Baseline absolute lymphocyte count and volumes of lung and spleen receiving ≥ 15 and ≥ 5 Gy, respectively, were the most important G4RIL risk determinants. The model achieved sensitivitytesting-set 0.798 and specificitytesting-set 0.667 with an area under the receiver operating characteristics curve (AUCtesting-set) of 0.783. The G4RIL risk for an average patient receiving protons increased by 19% had the patient switched to photons. Reductions in G4RIL risk were maximized with proton therapy for patients with older age, lower baseline absolute lymphocyte count, and higher lung and heart dose. CONCLUSION: G4RIL risk varies for individual patients with esophageal cancer and is modulated by radiotherapy dosimetric parameters. The framework for machine learning presented can be applied broadly to study risk determinants of other adverse events, providing the basis for adapting treatment strategies for mitigation.


Assuntos
Neoplasias Esofágicas , Linfopenia , Terapia com Prótons , Idoso , Neoplasias Esofágicas/radioterapia , Humanos , Linfopenia/diagnóstico , Linfopenia/epidemiologia , Linfopenia/etiologia , Aprendizado de Máquina , Terapia com Prótons/efeitos adversos , Estudos Retrospectivos
7.
J Immunol Res ; 2021: 8669098, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712741

RESUMO

Objective: This study explored the consistency and differences in the immune cells and cytokines between patients with COVID-19 or cancer. We further analyzed the correlations between the acute inflammation and cancer-related immune disorder. Methods: This retrospective study involved 167 COVID-19 patients and 218 cancer patients. COVID-19 and cancer were each further divided into two subgroups. Quantitative and qualitative variables were measured by one-way ANOVA and chi-square test, respectively. Herein, we carried out a correlation analysis between immune cells and cytokines and used receiver operating characteristic (ROC) curves to discover the optimal diagnostic index. Results: COVID-19 and cancers were associated with lymphopenia and high levels of monocytes, neutrophils, IL-6, and IL-10. IL-2 was the optimal indicator to differentiate the two diseases. Compared with respiratory cancer patients, COVID-19 patients had lower levels of IL-2 and higher levels of CD3+CD4+ T cells and CD19+ B cells. In the subgroup analysis, IL-6 was the optimal differential diagnostic parameter that had the ability to identify if COVID-19 patients would be severely affected, and severe COVID-19 patients had lower levels of lymphocyte subsets (CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+T cells, and CD19+ B cells) and CD16+CD56+ NK cells and higher level of neutrophils. There were significant differences in the levels of CD3+CD4+ T cells and CD19+ B cells between T1-2 and T3-4 stages as well as IL-2 and CD19+ B cells between N0-1 and N2-3 stages while no significant differences between the metastatic and nonmetastatic cancer patients. Additionally, there were higher correlations between IL-2 and IL-4, TNF-α and IL-2, TNF-α and IL-4, TNF-α and IFN-γ, and CD16+CD56+NK cells and various subsets of T cells in COVID-19 patients. There was a higher correlation between CD3+CD4+ T cells and CD19+ B cells in cancer patients. Conclusion: Inflammation associated with COVID-19 or cancer had effects on patients' outcomes. Accompanied by changes in immune cells and cytokines, there were consistencies, differences, and satisfactory correlations between patients with COVID-19 and those with cancers.


Assuntos
COVID-19/imunologia , Citocinas/sangue , Linfopenia/sangue , Monócitos/imunologia , Neoplasias/imunologia , Neutrófilos/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , COVID-19/diagnóstico , COVID-19/patologia , Feminino , Humanos , Inflamação/sangue , Inflamação/patologia , Células Matadoras Naturais/imunologia , Subpopulações de Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/patologia , Estudos Retrospectivos , SARS-CoV-2/imunologia , Adulto Jovem
8.
J Immunol Res ; 2021: 9822706, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712742

RESUMO

Background: Neutralizing antibody (nAb) response is generated following infection or immunization and plays an important role in the protection against a broad of viral infections. The role of nAb during clinical progression of coronavirus disease 2019 (COVID-19) remains little known. Methods: 123 COVID-19 patients during hospitalization in Tongji Hospital were involved in this retrospective study. The patients were grouped based on the severity and outcome. The nAb responses of 194 serum samples were collected from these patients within an investigation period of 60 days after the onset of symptoms and detected by a pseudotyped virus neutralization assay. The detail data about onset time, disease severity and laboratory biomarkers, treatment, and clinical outcome of these participants were obtained from electronic medical records. The relationship of longitudinal nAb changes with each clinical data was further assessed. Results: The nAb response in COVID-19 patients evidently experienced three consecutive stages, namely, rising, stationary, and declining periods. Patients with different severity and outcome showed differential dynamics of the nAb response over the course of disease. During the stationary phase (from 20 to 40 days after symptoms onset), all patients evolved nAb responses. In particular, high levels of nAb were elicited in severe and critical patients and older patients (≥60 years old). More importantly, critical but deceased COVID-19 patients showed high levels of several proinflammation cytokines, such as IL-2R, IL-8, and IL-6, and anti-inflammatory cytokine IL-10 in vivo, which resulted in lymphopenia, multiple organ failure, and the rapidly decreased nAb response. Conclusion: Our results indicate that nAb plays a crucial role in preventing the progression and deterioration of COVID-19, which has important implications for improving clinical management and developing effective interventions.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/imunologia , SARS-CoV-2/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Biomarcadores/sangue , COVID-19/patologia , Citocinas/sangue , Feminino , Humanos , Linfopenia/sangue , Linfopenia/imunologia , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Estudos Retrospectivos , Índice de Gravidade de Doença
9.
Front Cell Infect Microbiol ; 11: 670823, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490135

RESUMO

Objective: To analyze the epidemiological history, clinical symptoms, laboratory testing parameters of patients with mild and severe COVID-19 infection, and provide a reference for timely judgment of changes in the patients' conditions and the formulation of epidemic prevention and control strategies. Methods: A retrospective study was conducted in this research, a total of 90 patients with COVID-19 infection who received treatment from January 21 to March 31, 2020 in the Ninth People's Hospital of Dongguan City were selected as study subject. We analyzed the clinical characteristics of laboratory-confirmed patients with COVID-19, used the oversampling method (SMOTE) to solve the imbalance of categories, and established Lasso-logistic regression and random forest models. Results: Among the 90 confirmed COVID-19 cases, 79 were mild and 11 were severe. The average age of the patients was 36.1 years old, including 49 males and 41 females. The average age of severe patients is significantly older than that of mild patients (53.2 years old vs 33.7 years old). The average time from illness onset to hospital admission was 4.1 days and the average actual hospital stay was 18.7 days, both of these time actors were longer for severe patients than for mild patients. Forty-eight of the 90 patients (53.3%) had family cluster infections, which was similar among mild and severe patients. Comorbidities of underlying diseases were more common in severe patients, including hypertension, diabetes and other diseases. The most common symptom was cough [45 (50%)], followed by fever [43 (47.8%)], headache [7 (7.8%)], vomiting [3 (3.3%)], diarrhea [3 (3.3%)], and dyspnea [1 (1.1%)]. The laboratory findings of patients also included leukopenia [13(14.4%)] and lymphopenia (17.8%). Severe patients had a low level of creatine kinase (median 40.9) and a high level of D-dimer. The median NLR of severe patients was 2.82, which was higher than that of mild patients. Logistic regression showed that age, phosphocreatine kinase, procalcitonin, the lymphocyte count of the patient on admission, cough, fatigue, and pharynx dryness were independent predictors of COVID-19 severity. The classification of random forest was predicted and the importance of each variable was displayed. The variable importance of random forest indicates that age, D-dimer, NLR (neutrophil to lymphocyte ratio) and other top-ranked variables are risk factors. Conclusion: The clinical symptoms of COVID-19 patients are non-specific and complicated. Age and the time from onset to admission are important factors that determine the severity of the patient's condition. Patients with mild illness should be closely monitored to identify those who may become severe. Variables such as age and creatine phosphate kinase selected by logistic regression can be used as important indicators to assess the disease severity of COVID-19 patients. The importance of variables in the random forest further complements the variable feature information.


Assuntos
COVID-19 , Linfopenia , Adulto , China/epidemiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2
10.
PLoS Pathog ; 17(9): e1009850, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34473802

RESUMO

The Coronavirus Disease 2019 (COVID-19) is caused by the betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus that can mediate asymptomatic or fatal infections characterized by pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. Several studies have highlighted the importance of B and T lymphocytes, given that neutralizing antibodies and T cell responses are required for an effective immunity. In addition, other reports have described myeloid cells such as macrophages and monocytes play a major role in the immunity against SARS-CoV-2 as well as dysregulated pro-inflammatory signature that characterizes severe COVID-19. During COVID-19, neutrophils have been defined as a heterogeneous group of cells, functionally linked to severe inflammation and thrombosis triggered by degranulation and NETosis, but also to suppressive phenotypes. The physiological role of suppressive neutrophils during COVID-19 and their implications in severe disease have been poorly studied and is not well understood. Here, we discuss the current evidence regarding the role of neutrophils with suppressive properties such as granulocytic myeloid-derived suppressor cells (G-MDSCs) and their possible role in suppressing CD4+ and CD8+ T lymphocytes expansion and giving rise to lymphopenia in severe COVID-19 infection.


Assuntos
COVID-19/imunologia , Linfopenia/complicações , Neutrófilos/imunologia , SARS-CoV-2/fisiologia , Animais , COVID-19/sangue , COVID-19/complicações , Humanos , Linfopenia/sangue , Linfopenia/imunologia , Neutrófilos/virologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença
11.
Andes Pediatr ; 92(3): 395-405, 2021 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34479246

RESUMO

INTRODUCTION: In April 2020, the pediatric multisystem inflammatory syndrome temporarily associated with COVID-19 (MIS-C) was described for the first time. MIS-C could have a severe course and may require critical care support. OBJECTIVE: To describe the clinical, laboratory, and management characteristics of hospitalized children who meet MIS-C criteria with severe presentation in a pediatric critical pa tient unit. PATIENTS AND METHOD: Descriptive prospective study of children with severe MIS-C mana ged by treatment phases with immunoglobulin and methylprednisolone, according to their clinical response. Epidemiological, clinical, laboratory and imaging data were obtained. Phenotypes were classified into Kawasaki and not Kawasaki, comparing their findings. RESULTS: 20 patients were analy zed, the median age was 6 years, 60% were female, and 40% presented comorbidity. SARS-CoV-2 was detected in 90% of the patients. They presented fever as the first symptom, followed by brief and early gastrointestinal symptoms (70%). 75% presented the Kawasaki phenotype. They evolved with lymphopenia, hypoalbuminemia, coagulation alterations, and elevated systemic and cardiac in flammatory parameters. 80% of the cases presented echocardiographic alterations and 90% shock that required critical care support. All the patients had a short and favorable evolution. All patients responded to the established therapy, but 40% required a second phase of treatment. There were no differences when comparing phenotypes. No deaths were reported. CONCLUSION: MIS-C is a new childhood disease whose presentation could be life-threatening. It requires early suspicion, immuno modulatory management, critical care support, and a multidisciplinary approach to obtain the best results and optimize its prognosis.


Assuntos
COVID-19 , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/etiologia , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/terapia , Criança , Cuidados Críticos , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Hipoalbuminemia/etiologia , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Unidades de Terapia Intensiva Pediátrica , Linfopenia/etiologia , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Choque/etiologia , Choque/terapia , Avaliação de Sintomas , Síndrome de Resposta Inflamatória Sistêmica/complicações , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/terapia
14.
Mol Immunol ; 138: 121-127, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34392110

RESUMO

AIMS: Coronavirus disease 2019 (COVID-19) is a novel viral infection threatening worldwide health as currently there exists no effective treatment strategy and vaccination programs are not publicly available yet. T lymphocytes play an important role in antiviral defenses. However, T cell frequency and functionality may be affected during the disease. MATERIAL AND METHODS: Total blood samples were collected from patients with mild and severe COVID-19, and the total lymphocyte number, as well as CD4+ and CD8 + T cells were assessed using flowcytometry. Besides, the expression of exhausted T cell markers was evaluated. The levels of proinflammatory cytokines were also investigated in the serum of all patients using enzyme-linked immunesorbent assay (ELISA). Finally, the obtained results were analyzed along with laboratory serological reports. RESULTS: COVID-19 patients showed lymphopenia and reduced CD4+ and CD8 + T cells, as well as high percentage of PD-1 expression by T cells, especially in severe cases. Serum secretion of TNF-α, IL-1ß, and IL-2 receptor (IL-2R) were remarkably increased in patients with severe symptoms, as compared with healthy controls. Moreover, high levels of triglyceride (TG) and low density lipoprotein cholesterol (LDL-C), were correlated with the severity of the disease. CONCLUSION: Reduced number and function of T cells were observed in COVID-19 patients, especially in severe patients. Meanwhile, the secretion of proinflammatory cytokines was increased as the disease developed. High level of serum IL-2R was also considered as a sign of lymphopenia. Additionally, hypercholesterolemia and hyperlipidemia could be important prognostic factors in determining the severity of the infection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Linfopenia/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , COVID-19/metabolismo , COVID-19/virologia , LDL-Colesterol/sangue , Citocinas/sangue , Citocinas/imunologia , Citocinas/metabolismo , Progressão da Doença , Feminino , Humanos , Contagem de Linfócitos , Linfopenia/sangue , Linfopenia/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Triglicerídeos/sangue
15.
Viruses ; 13(7)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34372615

RESUMO

Lymphopenia is a frequent hematological manifestation, associated with a severe course of COVID-19, with an insufficiently understood pathogenesis. We present molecular genetic immunohistochemical, and electron microscopic data on SARS-CoV-2 dissemination and viral load (VL) in lungs, mediastinum lymph nodes, and the spleen of 36 patients who died from COVID-19. Lymphopenia <1 × 109/L was observed in 23 of 36 (63.8%) patients. In 12 of 36 cases (33%) SARS-CoV-2 was found in lung tissues only with a median VL of 239 copies (range 18-1952) SARS-CoV-2 cDNA per 100 copies of ABL1. Histomorphological changes corresponding to bronchopneumonia and the proliferative phase of DAD were observed in these cases. SARS-CoV-2 dissemination into the lungs, lymph nodes, and spleen was detected in 23 of 36 patients (58.4%) and was associated with the exudative phase of DAD in most of these cases. The median VL in the lungs was 12,116 copies (range 810-250281), lymph nodes-832 copies (range 96-11586), and spleen-71.5 copies (range 0-2899). SARS-CoV-2 in all cases belonged to the 19A strain. A immunohistochemical study revealed SARS-CoV-2 proteins in pneumocytes, alveolar macrophages, and bronchiolar epithelial cells in lung tissue, sinus histiocytes of lymph nodes, as well as cells of the Billroth pulp cords and spleen capsule. SARS-CoV-2 particles were detected by transmission electron microscopy in the cytoplasm of the endothelial cell, macrophages, and lymphocytes. The infection of lymphocytes with SARS-CoV-2 that we discovered for the first time may indicate a possible link between lymphopenia and SARS-CoV-2-mediated cytotoxic effect.


Assuntos
COVID-19/virologia , Pulmão/virologia , Linfonodos/virologia , Linfopenia/virologia , Mediastino/virologia , SARS-CoV-2/isolamento & purificação , Baço/virologia , Idoso , Idoso de 80 Anos ou mais , Teste para COVID-19 , Feminino , Humanos , Imuno-Histoquímica , Pulmão/patologia , Linfopenia/imunologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Carga Viral
16.
Cancer Radiother ; 25(6-7): 533-536, 2021 Oct.
Artigo em Francês | MEDLINE | ID: mdl-34462213

RESUMO

The abscopal effect has been mentioned since 1953. The increase in knowledge about the immune system and the development of immunotherapies support its potential therapeutic interest. While it is accepted that radiotherapy induces an immune response, demonstrating its systemic impact is not easy. The preclinical basis is solid but its clinical validation pending. Radiotherapy rarely induces tumor reduction at a distance from the beams, probably due to its immunosuppressive effect. This is why a synergy between radiotherapy and systemic treatments targeting these immunosuppressive mechanisms was observed. Several parameters can modulate the induction of the abscopal effect. Among these, the fractionation of the dose seems to be determining with currently a pre-eminence of hypofractionated stereotaxis. On the other hand, even if the choice of more immunogenic targets (liver, lung) should be favoured, the optimal number of lesions to be irradiated remains to be defined as well as the minimum volume allowing sufficient release of tumor antigens. The impact of radiation-induced lymphopenia on radiotherapy/immunotherapy efficacy needs to be assessed more precisely, as does the effect of radiotherapy techniques on them. Finally, the choice of immunotherapy(ies) and the combination regimen with radiotherapy remain under discussion. A sequential scheme appears to provide less toxicities but the concomitant would lead to a better response. The study of these different parameters should allow us to deliver optimized radiotherapy/immunotherapy(ies) combinations to our metastatic patients in order to benefit as many people as possible from this abscopal effect.


Assuntos
Imunoterapia/métodos , Metástase Neoplásica/radioterapia , Radioterapia/métodos , Antígenos de Neoplasias/imunologia , Terapia Combinada/métodos , Fracionamento da Dose de Radiação , Humanos , Sistema Imunitário/efeitos da radiação , Imunossupressão , Linfopenia/imunologia , Metástase Neoplásica/imunologia , Neoplasias/imunologia , Neoplasias/radioterapia , Radioterapia/efeitos adversos , Resultado do Tratamento
17.
Am J Perinatol ; 38(12): 1236-1243, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34396499

RESUMO

OBJECTIVE: This study aimed to determine if laboratory inflammatory markers can predict critical disease in symptomatic COVID-19 pregnant women. STUDY DESIGN: Multicenter, retrospective cohort study of all pregnant women presenting to New York City Health + Hospitals emergency departments from March 1 to May 30, 2020. We assessed all symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive pregnant women with room air oxygen saturation <95% on presentation. Logistic regression modeled the relationship of inflammatory markers to outcomes. Area under receiver operating characteristic (ROC) curve and maximum Youden index determined prognostic ability and optimal predictive cut-off values. RESULTS: A total of 498 of 5,002 pregnant women were SARS-CoV-2 RT-PCR positive of which 77 presented with hypoxemia. The absolute lymphocyte count (ALC) and neutrophil to lymphocyte ratio (NLR) were highly sensitive for progression to severe illness. ROC curve analysis identified predictive cutoffs: ALC < 1.49 × 109/L (96% sensitivity, 52% specificity, area under the receiver operating characteristic curve [AUC] = 0.80 (95% confidence interval [CI]: 0.70-0.90) and NLR >8.1 (100% sensitivity, 70% specificity, AUC = 0.86 (95% CI: [0.76-0.96]). CONCLUSION: ALC and NLR on presentation are sensitive markers of progression to critical COVID-19 disease in symptomatic pregnant women. This finding provides a practical, rapid method for assessment and can assist clinicians with decision-making regarding triage, level of care, and patient management. KEY POINTS: · Few tools exist to gauge risk of severe COVID-19 disease in pregnancy.. · ALC and NLR are sensitive predictive markers of disease progression in symptomatic women.. · Cut-off values for ALC and NLR will help direct patient triage and management..


Assuntos
COVID-19/complicações , Contagem de Linfócitos , Linfopenia/virologia , Neutrófilos/metabolismo , Complicações Infecciosas na Gravidez/virologia , Índice de Gravidade de Doença , Adulto , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Sensibilidade e Especificidade
18.
PLoS One ; 16(8): e0254845, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34358240

RESUMO

BACKGROUND: Hematopoietic stem cell transplantation is a potential cure for certain life-threatening malignant and nonmalignant diseases. However, experimental and clinical studies have demonstrated that pre-transplant myeloablative conditioning damages the gut leading to translocation of intestinal bacteria and the development of acute graft vs. host disease (aGVHD). The overall objective of this study was to determine whether administration of broad spectrum antibiotics (Abx) affects the onset and/or severity of aGVHD in lymphopenic mice that were not subjected to toxic, pre-transplant conditioning. RESULTS: We found that treatment of NK cell-depleted recombination activating gene-1-deficient (-NK/RAG) recipients with an Abx cocktail containing vancomycin and neomycin for 7 days prior to and 4 weeks following adoptive transfer of allogeneic CD4+ T cells, exacerbated the development of aGVHD-induced BM failure and spleen damage when compared to untreated-NK/RAG recipients engrafted with syngeneic or allogeneic T cells. Abx-treated mice exhibited severe anemia and monocytopenia as well as marked reductions in BM- and spleen-residing immune cells. Blinded histopathological analysis confirmed that Abx-treated mice engrafted with allogeneic T cells suffered significantly more damage to the BM and spleen than did untreated mice engrafted with allogeneic T cells. Abx-induced exacerbation of BM and spleen damage correlated with a dramatic reduction in fecal bacterial diversity, marked loss of anaerobic bacteria and remarkable expansion of potentially pathogenic bacteria. CONCLUSIONS: We conclude that continuous Abx treatment may aggravate aGVHD-induced tissue damage by reducing short chain fatty acid-producing anaerobes (e.g. Clostridium, Blautia) and/or by promoting the expansion of pathobionts (e.g. Akkermansia) and opportunistic pathogens (Cronobacter).


Assuntos
Antibacterianos/uso terapêutico , Medula Óssea/patologia , Progressão da Doença , Doença Enxerto-Hospedeiro/tratamento farmacológico , Linfopenia/tratamento farmacológico , Baço/patologia , Doença Aguda , Transferência Adotiva , Animais , Antibacterianos/farmacologia , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Contagem de Células Sanguíneas , Medula Óssea/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Citocinas/sangue , Fezes/microbiologia , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/patologia , Inflamação/sangue , Inflamação/complicações , Inflamação/patologia , Linfopenia/sangue , Linfopenia/complicações , Masculino , Camundongos , Filogenia , Baço/efeitos dos fármacos , Transplante Homólogo
19.
Cells ; 10(8)2021 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-34440787

RESUMO

Adoptive cell therapy (ACT) using tumor-reactive T cells is a promising form of immunotherapy to specifically target cancer. However, the survival and functional maintenance of adoptively transferred T cells remains a challenge, ultimately limiting their efficacy. Here, we evaluated the use of recombinant IL7-Fc in ACT. In a lymphopenic murine melanoma model, IL7-Fc treatment led to the enhanced inhibition of tumor growth with an increased number of adoptively transferred CD8+ T cells in tumor tissue and tumor-draining lymph nodes. Additionally, IL7-Fc further enhanced anti-tumor responses that were induced by recombinant human IL2 in the same mouse model. In contrast, in an immunocompetent murine melanoma model, IL7-Fc dampened the anti-tumor immunity. Further, IL7-Fc decreased the proliferation of adoptively transferred and immune-activated tumor-reactive CD8+ T cells in immunocompetent mice by inducing the massive expansion of endogenous T cells, thereby limiting the space for adoptively transferred T cells. Our data suggest that IL7-Fc is principally beneficial for enhancing the efficacy of tumor-reactive T-cells in lymphopenic conditions for the ACT.


Assuntos
Fragmentos Fc das Imunoglobulinas/imunologia , Imunoterapia Adotiva/métodos , Interleucina-7/imunologia , Linfopenia/imunologia , Melanoma Experimental/terapia , Proteínas Recombinantes de Fusão/administração & dosagem , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/metabolismo , Interleucina-7/genética , Interleucina-7/metabolismo , Contagem de Leucócitos , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Linfopenia/metabolismo , Melanoma Experimental/genética , Melanoma Experimental/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Células Mieloides/citologia , Células Mieloides/efeitos dos fármacos , Células Mieloides/imunologia , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...