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1.
J Orthop Surg Res ; 16(1): 415, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193239

RESUMO

BACKGROUND: Recent studies indicate that, in addition to antibody production, lymphocyte responses to SARS-CoV-2 may play an important role in protective immunity to COVID-19 and a percentage of the general population may exhibit lymphocyte memory due to unknown/asymptomatic exposure to SARS-CoV-2 or cross-reactivity to other more common coronaviruses pre-vaccination. Total joint replacement (TJR) candidates returning to elective surgeries (median age 68 years) may exhibit similar lymphocyte and/or antibody protection to COVID-19 prior to vaccination METHODS: In this retrospective study, we analyzed antibody titters, lymphocyte memory, and inflammatory biomarkers specific for the Spike and Nucleocapsid proteins of the SARS-CoV-2 virus in a cohort of n=73 returning TJR candidates (knees and/or hips) pre-operatively. RESULTS: Peripheral blood serum of TJR candidate patients exhibited a positivity rate of 18.4% and 4% for IgG antibodies specific for SARS-CoV-2 nucleocapsid and spike proteins, respectively. 13.5% of TJR candidates exhibited positive lymphocyte reactivity (SI > 2) to the SARS-CoV-2 nucleocapsid protein and 38% to the spike protein. SARS-CoV-2 reactive lymphocytes exhibited a higher production of inflammatory biomarkers (i.e., IL-1ß, IL-6, TNFα, and IL-1RA) compared to non-reactive lymphocytes. CONCLUSIONS: A percentage of TJR candidates returning for elective surgeries exhibit pre-vaccination positive SARS-CoV-2 antibodies and T cell memory responses with associated pro-inflammatory biomarkers. This is an important parameter for understanding immunity, risk profiles, and may aid pre-operative planning. TRIAL REGISTRATION: Retrospectively registered.


Assuntos
Artroplastia de Substituição , COVID-19/imunologia , Inflamação/metabolismo , Linfócitos/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Período Pré-Operatório , Estudos Retrospectivos
2.
J Orthop Surg Res ; 16(1): 415, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: covidwho-1286829

RESUMO

BACKGROUND: Recent studies indicate that, in addition to antibody production, lymphocyte responses to SARS-CoV-2 may play an important role in protective immunity to COVID-19 and a percentage of the general population may exhibit lymphocyte memory due to unknown/asymptomatic exposure to SARS-CoV-2 or cross-reactivity to other more common coronaviruses pre-vaccination. Total joint replacement (TJR) candidates returning to elective surgeries (median age 68 years) may exhibit similar lymphocyte and/or antibody protection to COVID-19 prior to vaccination METHODS: In this retrospective study, we analyzed antibody titters, lymphocyte memory, and inflammatory biomarkers specific for the Spike and Nucleocapsid proteins of the SARS-CoV-2 virus in a cohort of n=73 returning TJR candidates (knees and/or hips) pre-operatively. RESULTS: Peripheral blood serum of TJR candidate patients exhibited a positivity rate of 18.4% and 4% for IgG antibodies specific for SARS-CoV-2 nucleocapsid and spike proteins, respectively. 13.5% of TJR candidates exhibited positive lymphocyte reactivity (SI > 2) to the SARS-CoV-2 nucleocapsid protein and 38% to the spike protein. SARS-CoV-2 reactive lymphocytes exhibited a higher production of inflammatory biomarkers (i.e., IL-1ß, IL-6, TNFα, and IL-1RA) compared to non-reactive lymphocytes. CONCLUSIONS: A percentage of TJR candidates returning for elective surgeries exhibit pre-vaccination positive SARS-CoV-2 antibodies and T cell memory responses with associated pro-inflammatory biomarkers. This is an important parameter for understanding immunity, risk profiles, and may aid pre-operative planning. TRIAL REGISTRATION: Retrospectively registered.


Assuntos
Artroplastia de Substituição , COVID-19/imunologia , Inflamação/metabolismo , Linfócitos/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Período Pré-Operatório , Estudos Retrospectivos
3.
Medicine (Baltimore) ; 100(25): e26437, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160435

RESUMO

ABSTRACT: Recent studies have shown that some inflammatory markers are associated with the prognosis of solid tumors. This study aims to evaluate the prognosis of glioma patients with or without adjuvant treatment using the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR).All patients who were diagnosed with gliomas at the first and second affiliated hospital of Guangxi Medical University between 2011 and 2020 were included in this study. The optimal cutoff value of SII, NLR, and PLR was determined by X-tile software program. We stratified patients into several groups and evaluated the progression-free survival (PFS) and overall survival (OS) of SII, NLR, and PLR during the period of pre-surgical, con-chemoradiotherapy, and post-treatments. Multivariate Cox regression analyses were performed to detect the relationships between OS, PFS, and prognostic variables.A total of 67 gliomas patients were enrolled in the study. The cutoff values of SII, NLR, and PLR were 781.5 × 109/L, 2.9 × 109/L, and 123.2 × 109/L, respectively. Patients who are pre-SII < 781.5 × 109/L had better PFS (P = .027), but no difference in OS. In addition, patients who had low pre-NLR (<2.9 × 109/L) meant better OS and PFS. PLR after adjuvant treatments (post-PLR) was significantly higher than pre-PLR (P = .035). Multivariate analyses revealed that pre-SII, pre-NLR were independent prognostic factors for OS (pre-SII: HR 1.002, 95% CI: 1.000-1.005, P = .030 and pre-PLR: HR 0.983, 95% CI: 0.973-0.994, P = .001), while pre-PLR was an independent factor for PFS (HR 0.989, 95% CI: 0.979-1.000, P = .041).High pre-SII or high pre-NLR could be prognostic markers to identify glioma patients who had a poor prognosis.


Assuntos
Plaquetas/imunologia , Neoplasias Encefálicas/terapia , Glioma/terapia , Linfócitos/imunologia , Procedimentos Neurocirúrgicos , Neutrófilos/imunologia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/mortalidade , Quimiorradioterapia/métodos , Feminino , Glioma/sangue , Glioma/imunologia , Glioma/mortalidade , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Contagem de Plaquetas , Período Pré-Operatório , Prognóstico , Intervalo Livre de Progressão , Valores de Referência , Estudos Retrospectivos , Adulto Jovem
4.
Medicine (Baltimore) ; 100(25): e26506, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160470

RESUMO

ABSTRACT: Many clinical studies have demonstrated that the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and Onodera's prognostic nutritional index (OPNI) are visibly involved in the prognosis of a variety of tumors. In our research, we aim to determin the prognostic impact of NLR, PLR, and OPNI for hepatocellular carcinoma (HCC).Data of hepatocellular carcinoma patients undergoing treatment in Changzhi People's Hospital between 2011 and 2017 were reviewed. 270 patients with HCC were under inclusion criteria. The optimal cut-off points of OPNI, NLR and PLR were determined by using the X-tile program. The overall survival (OS) was analyzed by Kaplan-Meier method. Multivariate analysis was performed using Cox Proportional Hazard Regression model to determine independent prognostic indicators for HCC.As revealed by Univariate and multivariate analysis, OPNI, Treatment, PLR, and BCLC Stage can be used as independent prognostic indicators for HCC. Comparing the P values and hazard ratios, we found out that the OPNI has greatest influence on prognosis in these indexes. The appropriate cut-off points of NLR, PLR, and OPNI were 2.5, 133.3, and 39.5, respectively. High score OPNI group had a better OS. In the analysis between OPNI and clinicopathological characteristics, there were differences in treatment, postoperative therapy, AST, ALBI grade, NLR and PLR between the high OPNI group and the low OPNI group, while others did not.OPNI is a straightforward and effective independent prognostic indicator for HCC.


Assuntos
Plaquetas/imunologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Linfócitos/imunologia , Neutrófilos/imunologia , Avaliação Nutricional , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Quimioterapia Adjuvante , Feminino , Hepatectomia , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Estimativa de Kaplan-Meier , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/terapia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Valores de Referência , Estudos Retrospectivos
5.
Sci Rep ; 11(1): 13350, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172816

RESUMO

Coronavirus disease 2019 (COVID-19) is a pandemic viral disease affecting also obstetric patients and uncertainties exist about the prognostic role of inflammatory biomarkers and hemocytometry values in patients with this infection. To clarify that, we have assessed the values of several inflammatory biomarkers and hemocytometry variables in a cohort of obstetric patients hospitalized with COVID-19 and we have correlated the values at admission with the need of oxygen supplementation during the hospitalization. Overall, among 62 (27.3%) pregnant women and 165 (72.7%) postpartum women, 21 (9.2%) patients received oxygen supplementation and 2 (0.9%) required admission to intensive care unit but none died. During hospitalization leukocytes (p < 0.001), neutrophils (p < 0.001), neutrophils to lymphocytes ratio (p < 0.001) and C reactive protein (p < 0.001) decreased significantly, whereas lymphocytes (p < 0.001), platelets (p < 0.001) and ferritin (p = 0.001) increased. Lymphocyte values at admission were correlated with oxygen need, with a 26% higher risk of oxygen supplementation for each 1000 cells decreases. Overall, in obstetric patients hospitalized with COVID-19, C reactive protein is the inflammatory biomarker that better mirrors the course of the disease whereas D-dimer or ferritin are not reliable predictors of poor outcome. Care to the need of oxygen supplementation should be reserved to patients with reduced lymphocyte values at admission.


Assuntos
Proteína C-Reativa/imunologia , COVID-19 , Produtos de Degradação da Fibrina e do Fibrinogênio/imunologia , Linfócitos , Adulto , Biomarcadores/sangue , COVID-19/epidemiologia , COVID-19/imunologia , Feminino , Humanos , Linfócitos/citologia , Linfócitos/imunologia , Gravidez , Estudos Retrospectivos
6.
Int J Mol Sci ; 22(9)2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-34065088

RESUMO

Loss of function KCNK3 mutation is one of the gene variants driving hereditary pulmonary arterial hypertension (PAH). KCNK3 is expressed in several cell and tissue types on both membrane and endoplasmic reticulum and potentially plays a role in multiple pathological process associated with PAH. However, the role of various stressors driving the susceptibility of KCNK3 mutation to PAH is unknown. Hence, we exposed kcnk3fl/fl animals to hypoxia, metabolic diet and low dose lipopolysaccharide (LPS) and performed molecular characterization of their tissue. We also used tissue samples from KCNK3 patients (skin fibroblast derived inducible pluripotent stem cells, blood, lungs, peripheral blood mononuclear cells) and performed microarray, immunohistochemistry (IHC) and mass cytometry time of flight (CyTOF) experiments. Although a hypoxic insult did not alter vascular tone in kcnk3fl/fl mice, RNASeq study of these lungs implied that inflammatory and metabolic factors were altered, and the follow-up diet study demonstrated a dysregulation of bone marrow cells in kcnk3fl/fl mice. Finally, a low dose LPS study clearly showed that inflammation could be a possible second hit driving PAH in kcnk3fl/fl mice. Multiplex, IHC and CyTOF immunophenotyping studies on human samples confirmed the mouse data and strongly indicated that cell mediated, and innate immune responses may drive PAH susceptibility in these patients. In conclusion, loss of function KCNK3 mutation alters various physiological processes from vascular tone to metabolic diet through inflammation. Our data suggests that altered circulating immune cells may drive PAH susceptibility in patients with KCNK3 mutation.


Assuntos
Imunomodulação/genética , Mutação , Proteínas do Tecido Nervoso/genética , Canais de Potássio de Domínios Poros em Tandem/genética , Hipertensão Arterial Pulmonar/genética , Hipertensão Arterial Pulmonar/imunologia , Animais , Biomarcadores , Estudos de Casos e Controles , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos , Camundongos Knockout , Modelos Biológicos , Monócitos/imunologia , Monócitos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Hipertensão Arterial Pulmonar/complicações , Hipertensão Arterial Pulmonar/fisiopatologia , Transcriptoma
7.
Cell ; 184(13): 3573-3587.e29, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34062119

RESUMO

The simultaneous measurement of multiple modalities represents an exciting frontier for single-cell genomics and necessitates computational methods that can define cellular states based on multimodal data. Here, we introduce "weighted-nearest neighbor" analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of 211,000 human peripheral blood mononuclear cells (PBMCs) with panels extending to 228 antibodies to construct a multimodal reference atlas of the circulating immune system. Multimodal analysis substantially improves our ability to resolve cell states, allowing us to identify and validate previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets and to interpret immune responses to vaccination and coronavirus disease 2019 (COVID-19). Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets and to look beyond the transcriptome toward a unified and multimodal definition of cellular identity.


Assuntos
SARS-CoV-2/imunologia , Análise de Célula Única/métodos , Células 3T3 , Animais , COVID-19/imunologia , Linhagem Celular , Perfilação da Expressão Gênica/métodos , Humanos , Imunidade/imunologia , Leucócitos Mononucleares/imunologia , Linfócitos/imunologia , Camundongos , Análise de Sequência de RNA/métodos , Transcriptoma/imunologia , Vacinação
8.
Sci Rep ; 11(1): 13350, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: covidwho-1281743

RESUMO

Coronavirus disease 2019 (COVID-19) is a pandemic viral disease affecting also obstetric patients and uncertainties exist about the prognostic role of inflammatory biomarkers and hemocytometry values in patients with this infection. To clarify that, we have assessed the values of several inflammatory biomarkers and hemocytometry variables in a cohort of obstetric patients hospitalized with COVID-19 and we have correlated the values at admission with the need of oxygen supplementation during the hospitalization. Overall, among 62 (27.3%) pregnant women and 165 (72.7%) postpartum women, 21 (9.2%) patients received oxygen supplementation and 2 (0.9%) required admission to intensive care unit but none died. During hospitalization leukocytes (p < 0.001), neutrophils (p < 0.001), neutrophils to lymphocytes ratio (p < 0.001) and C reactive protein (p < 0.001) decreased significantly, whereas lymphocytes (p < 0.001), platelets (p < 0.001) and ferritin (p = 0.001) increased. Lymphocyte values at admission were correlated with oxygen need, with a 26% higher risk of oxygen supplementation for each 1000 cells decreases. Overall, in obstetric patients hospitalized with COVID-19, C reactive protein is the inflammatory biomarker that better mirrors the course of the disease whereas D-dimer or ferritin are not reliable predictors of poor outcome. Care to the need of oxygen supplementation should be reserved to patients with reduced lymphocyte values at admission.


Assuntos
Proteína C-Reativa/imunologia , COVID-19 , Produtos de Degradação da Fibrina e do Fibrinogênio/imunologia , Linfócitos , Adulto , Biomarcadores/sangue , COVID-19/epidemiologia , COVID-19/imunologia , Feminino , Humanos , Linfócitos/citologia , Linfócitos/imunologia , Gravidez , Estudos Retrospectivos
9.
Cytokine ; 144: 155593, 2021 08.
Artigo em Inglês | MEDLINE | ID: covidwho-1242912

RESUMO

An analysis of published data appertaining to the cytokine storms of COVID-19, H1N1 influenza, cytokine release syndrome (CRS), and macrophage activation syndrome (MAS) reveals many common immunological and biochemical abnormalities. These include evidence of a hyperactive coagulation system with elevated D-dimer and ferritin levels, disseminated intravascular coagulopathy (DIC) and microthrombi coupled with an activated and highly permeable vascular endothelium. Common immune abnormalities include progressive hypercytokinemia with elevated levels of TNF-α, interleukin (IL)-6, and IL-1ß, proinflammatory chemokines, activated macrophages and increased levels of nuclear factor kappa beta (NFκB). Inflammasome activation and release of damage associated molecular patterns (DAMPs) is common to COVID-19, H1N1, and MAS but does not appear to be a feature of CRS. Elevated levels of IL-18 are detected in patients with COVID-19 and MAS but have not been reported in patients with H1N1 influenza and CRS. Elevated interferon-γ is common to H1N1, MAS, and CRS but levels of this molecule appear to be depressed in patients with COVID-19. CD4+ T, CD8+ and NK lymphocytes are involved in the pathophysiology of CRS, MAS, and possibly H1N1 but are reduced in number and dysfunctional in COVID-19. Additional elements underpinning the pathophysiology of cytokine storms include Inflammasome activity and DAMPs. Treatment with anakinra may theoretically offer an avenue to positively manipulate the range of biochemical and immune abnormalities reported in COVID-19 and thought to underpin the pathophysiology of cytokine storms beyond those manipulated via the use of, canakinumab, Jak inhibitors or tocilizumab. Thus, despite the relative success of tocilizumab in reducing mortality in COVID-19 patients already on dexamethasone and promising results with Baricitinib, the combination of anakinra in combination with dexamethasone offers the theoretical prospect of further improvements in patient survival. However, there is currently an absence of trial of evidence in favour or contravening this proposition. Accordingly, a large well powered blinded prospective randomised controlled trial (RCT) to test this hypothesis is recommended.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , COVID-19 , Síndrome da Liberação de Citocina , Vírus da Influenza A Subtipo H1N1/imunologia , SARS-CoV-2/imunologia , COVID-19/tratamento farmacológico , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/patologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/patologia , Intervalo Livre de Doença , Humanos , Influenza Humana/tratamento farmacológico , Influenza Humana/imunologia , Influenza Humana/mortalidade , Influenza Humana/patologia , Janus Quinases/antagonistas & inibidores , Janus Quinases/metabolismo , Linfócitos/imunologia , Linfócitos/patologia , Taxa de Sobrevida
10.
Emerg Microbes Infect ; 10(1): 1156-1168, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: covidwho-1249264

RESUMO

ABSTRACTThe risk of secondary infection with SARS-CoV-2 and influenza A virus is becoming a practical problem that must be addressed as the flu season merges with the COVID-19 pandemic. As SARS-CoV-2 and influenza A virus have been found in patients, understanding the in vivo characteristics of the secondary infection between these two viruses is a high priority. Here, hACE2 transgenic mice were challenged with the H1N1 virus at a nonlethal dose during the convalescent stage on 7 and 14 days post SARS-CoV-2 infection, and importantly, subsequent H1N1 infection showed enhanced viral shedding and virus tissue distribution. Histopathological observation revealed an extensive pathological change in the lungs related to H1N1 infection in mice recovered from SARS-CoV-2 infection, with severe inflammation infiltration and bronchiole disruption. Moreover, upon H1N1 exposure on 7 and 14 dpi of SARS-CoV-2 infection, the lymphocyte population activated at a lower level with T cell suppressed in both PBMC and lung. These findings will be valuable for evaluating antiviral therapeutics and vaccines as well as guiding public health work.


Assuntos
Lesão Pulmonar Aguda/patologia , Enzima de Conversão de Angiotensina 2/genética , COVID-19/patologia , Infecções por Orthomyxoviridae/patologia , Lesão Pulmonar Aguda/virologia , Animais , COVID-19/terapia , Coinfecção/patologia , Coinfecção/virologia , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Pulmão/patologia , Contagem de Linfócitos , Linfócitos/imunologia , Camundongos , Camundongos Transgênicos , Infecções por Orthomyxoviridae/terapia , SARS-CoV-2/isolamento & purificação , Carga Viral , Replicação Viral/fisiologia , Eliminação de Partículas Virais/fisiologia
11.
Cell ; 184(13): 3573-3587.e29, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: covidwho-1248834

RESUMO

The simultaneous measurement of multiple modalities represents an exciting frontier for single-cell genomics and necessitates computational methods that can define cellular states based on multimodal data. Here, we introduce "weighted-nearest neighbor" analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of 211,000 human peripheral blood mononuclear cells (PBMCs) with panels extending to 228 antibodies to construct a multimodal reference atlas of the circulating immune system. Multimodal analysis substantially improves our ability to resolve cell states, allowing us to identify and validate previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets and to interpret immune responses to vaccination and coronavirus disease 2019 (COVID-19). Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets and to look beyond the transcriptome toward a unified and multimodal definition of cellular identity.


Assuntos
SARS-CoV-2/imunologia , Análise de Célula Única/métodos , Células 3T3 , Animais , COVID-19/imunologia , Linhagem Celular , Perfilação da Expressão Gênica/métodos , Humanos , Imunidade/imunologia , Leucócitos Mononucleares/imunologia , Linfócitos/imunologia , Camundongos , Análise de Sequência de RNA/métodos , Transcriptoma/imunologia , Vacinação
12.
Cytokine ; 144: 155593, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34074585

RESUMO

An analysis of published data appertaining to the cytokine storms of COVID-19, H1N1 influenza, cytokine release syndrome (CRS), and macrophage activation syndrome (MAS) reveals many common immunological and biochemical abnormalities. These include evidence of a hyperactive coagulation system with elevated D-dimer and ferritin levels, disseminated intravascular coagulopathy (DIC) and microthrombi coupled with an activated and highly permeable vascular endothelium. Common immune abnormalities include progressive hypercytokinemia with elevated levels of TNF-α, interleukin (IL)-6, and IL-1ß, proinflammatory chemokines, activated macrophages and increased levels of nuclear factor kappa beta (NFκB). Inflammasome activation and release of damage associated molecular patterns (DAMPs) is common to COVID-19, H1N1, and MAS but does not appear to be a feature of CRS. Elevated levels of IL-18 are detected in patients with COVID-19 and MAS but have not been reported in patients with H1N1 influenza and CRS. Elevated interferon-γ is common to H1N1, MAS, and CRS but levels of this molecule appear to be depressed in patients with COVID-19. CD4+ T, CD8+ and NK lymphocytes are involved in the pathophysiology of CRS, MAS, and possibly H1N1 but are reduced in number and dysfunctional in COVID-19. Additional elements underpinning the pathophysiology of cytokine storms include Inflammasome activity and DAMPs. Treatment with anakinra may theoretically offer an avenue to positively manipulate the range of biochemical and immune abnormalities reported in COVID-19 and thought to underpin the pathophysiology of cytokine storms beyond those manipulated via the use of, canakinumab, Jak inhibitors or tocilizumab. Thus, despite the relative success of tocilizumab in reducing mortality in COVID-19 patients already on dexamethasone and promising results with Baricitinib, the combination of anakinra in combination with dexamethasone offers the theoretical prospect of further improvements in patient survival. However, there is currently an absence of trial of evidence in favour or contravening this proposition. Accordingly, a large well powered blinded prospective randomised controlled trial (RCT) to test this hypothesis is recommended.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , COVID-19 , Síndrome da Liberação de Citocina , Vírus da Influenza A Subtipo H1N1/imunologia , SARS-CoV-2/imunologia , COVID-19/tratamento farmacológico , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/patologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/patologia , Intervalo Livre de Doença , Humanos , Influenza Humana/tratamento farmacológico , Influenza Humana/imunologia , Influenza Humana/mortalidade , Influenza Humana/patologia , Janus Quinases/antagonistas & inibidores , Janus Quinases/metabolismo , Linfócitos/imunologia , Linfócitos/patologia , Taxa de Sobrevida
13.
Emerg Microbes Infect ; 10(1): 1156-1168, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34060982

RESUMO

ABSTRACTThe risk of secondary infection with SARS-CoV-2 and influenza A virus is becoming a practical problem that must be addressed as the flu season merges with the COVID-19 pandemic. As SARS-CoV-2 and influenza A virus have been found in patients, understanding the in vivo characteristics of the secondary infection between these two viruses is a high priority. Here, hACE2 transgenic mice were challenged with the H1N1 virus at a nonlethal dose during the convalescent stage on 7 and 14 days post SARS-CoV-2 infection, and importantly, subsequent H1N1 infection showed enhanced viral shedding and virus tissue distribution. Histopathological observation revealed an extensive pathological change in the lungs related to H1N1 infection in mice recovered from SARS-CoV-2 infection, with severe inflammation infiltration and bronchiole disruption. Moreover, upon H1N1 exposure on 7 and 14 dpi of SARS-CoV-2 infection, the lymphocyte population activated at a lower level with T cell suppressed in both PBMC and lung. These findings will be valuable for evaluating antiviral therapeutics and vaccines as well as guiding public health work.


Assuntos
Lesão Pulmonar Aguda/patologia , Enzima de Conversão de Angiotensina 2/genética , COVID-19/patologia , Infecções por Orthomyxoviridae/patologia , Lesão Pulmonar Aguda/virologia , Animais , COVID-19/terapia , Coinfecção/patologia , Coinfecção/virologia , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Pulmão/patologia , Contagem de Linfócitos , Linfócitos/imunologia , Camundongos , Camundongos Transgênicos , Infecções por Orthomyxoviridae/terapia , SARS-CoV-2/isolamento & purificação , Carga Viral , Replicação Viral/fisiologia , Eliminação de Partículas Virais/fisiologia
14.
Medicine (Baltimore) ; 100(23): e26288, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115032

RESUMO

ABSTRACT: The leukocytes play an important role in immune function during sepsis. We performed a retrospective study to investigate if leukocytes kinetics was associated with survival in critically ill patients with septic shock in intensive care unit (ICU).Patients with septic shock from January 1, 2014 to June 30, 2018 in our ICU were included. We extracted the demographic, clinical and laboratory data, comorbidities from our clinical database. The number of white blood cell, neutrophil and lymphocyte on day 1 and day 3 after diagnosis were collected and neutrophil to lymphocyte ratios (NLR) were calculated. Our primary outcome was 28-day mortality. Univariate and multivariate logistic regression models and cox proportional risk model were used to analyze the association between the leukocytes kinetics during first 3 days after ICU admission and the day-28 mortality.A total of 1245 septic shock patients with a 28-day mortality of 35.02% were included into analysis. There were no significant difference of lymphocyte number (0.83 ±â€Š0.02 vs 0.80 ±â€Š0.04, P = .552) between survival and non-survivals on day 1. However, the lymphocyte counts was significantly lower (0.95 ±â€Š0.03 vs 0.85 ±â€Š0.04, P = .024) on the third day. Both multivariate logistic and Cox regression analysis showed that lymphocyte counts on day 3 were associated with day-28 mortality. Moreover, Kaplan-Meier survival analysis revealed that increasing in lymphocyte counts and decreasing WBC, neutrophils and NLR during the first 3 days after diagnosis were associated with longer survival.Leukocytes kinetics during the first 3 days is a valuable prognostic marker in patients with septic shock in the ICU.


Assuntos
Ensaios de Migração Celular/métodos , Contagem de Leucócitos , Linfócitos/imunologia , Neutrófilos/imunologia , Choque Séptico , China , Cuidados Críticos/métodos , Estado Terminal/terapia , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Estimativa de Kaplan-Meier , Contagem de Leucócitos/métodos , Contagem de Leucócitos/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Choque Séptico/diagnóstico , Choque Séptico/imunologia , Choque Séptico/mortalidade
15.
Medicine (Baltimore) ; 100(23): e26292, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115033

RESUMO

ABSTRACT: Minute clear cell renal cell carcinoma (MccRCC) has a diameter of <1.5 cm and can be diagnosed using multi-slice spiral CT (MSCT). Recently, the role of the neutrophil-lymphocyte ratio (NLR) in the development of MccRCC has attracted attention. This study aimed to further explore the relationship between the NLR and MccRCC.This was a prospective study of 100 patients who were diagnosed with MccRCC using MSCT at Urumqi Friendship Hospital, China. The study investigated a series of pretreatment factors, including NLR and patients' general clinical data. Statistical methods employed included Pearson's chi-square test, Spearman-rho correlation test, Cox regression analysis, and receiver operator characteristic curve analysis.Based on Pearson's χ2, Spearman-rho test, and univariate/multivariate Cox regression analysis, the overall survival of patients with MccRCC was shown to be significantly related to NLR (P < .001). NLR (hazard ratio = 50.676, 95%CI, 17.543-146.390, P < .001) is a significant independent risk-factor for MccRCC. A receiver operator characteristic curve was plotted to examine specificity and sensitivity between NLR and MccRCC (area under curve = 0.958, P < .001).The level of the NLR plays a crucial role in the survival of patients with MccRCC, as diagnosed with MSCT. The higher the NLR, the worse the prognosis for patients with MccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Linfócitos/imunologia , Neutrófilos/imunologia , Tomografia Computadorizada Espiral/métodos , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , China , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/sangue , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Contagem de Leucócitos/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Sensibilidade e Especificidade
16.
Front Immunol ; 12: 605857, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046028

RESUMO

Aims: Latent cytomegalovirus (CMV) infection is associated with adverse cardiovascular outcomes. Virus-specific CX3CR1+ effector memory T-cells may be instrumental in this process due to their pro-inflammatory properties. We investigated the role of CX3CR1 (fractalkine receptor) in CMV-related lymphocyte kinetics and cardiac remodeling in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). Methods and Results: We retrospectively analysed lymphocyte count, troponin, and survival in 4874 STEMI/pPCI patients, evaluated lymphocyte kinetics during reperfusion in a prospective cohort, and obtained sequential cardiac MRI (cMRI) to assess remodeling. Pre-reperfusion lymphopenia independently predicted mortality at 7.5 years. Prior to reperfusion, CCR7+ T-lymphocytes appeared to be depleted. After reperfusion, T-lymphocytes expressing CX3CR1 were depleted predominantly in CMV-seropositive patients. During ischaemia/reperfusion, a drop in CX3CR1+ T-lymphocytes was significantly linked with microvascular obstruction in CMV+ patients, suggesting increased fractalkine-receptor interaction. At 12 weeks, CMV+ patients displayed adverse LV remodeling. Conclusion: We show that lymphopenia occurs before and after reperfusion in STEMI by different mechanisms and predicts long-term outcome. In CMV+ patients, increased fractalkine induction and sequestration of CX3CR1+ T-cells may contribute to adverse remodeling, suggesting a pro-inflammatory pathomechanism which presents a novel therapeutic target.


Assuntos
Receptor 1 de Quimiocina CX3C/genética , Infecções por Citomegalovirus/complicações , Linfócitos/metabolismo , Infarto do Miocárdio/complicações , Infarto do Miocárdio/metabolismo , Remodelação Ventricular , Idoso , Biomarcadores , Receptor 1 de Quimiocina CX3C/metabolismo , Citomegalovirus , Infecções por Citomegalovirus/virologia , Feminino , Testes de Função Cardíaca , Humanos , Imunofenotipagem , Linfócitos/imunologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Receptores CCR7/metabolismo , Remodelação Ventricular/genética , Remodelação Ventricular/imunologia
17.
Front Immunol ; 12: 586320, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936027

RESUMO

Since the first description of the syndrome of sideroblastic anemia with immunodeficiency, fevers and development delay (SIFD), clinical pictures lacking both neurological and hematological manifestations have been reported. Moreover, prominent skin involvement, such as with relapsing erythema nodosum, is not a common finding. Up to this moment, no genotype and phenotype correlation could be done, but mild phenotypes seem to be located in the N or C part. B-cell deficiency is a hallmark of SIFD syndrome, and multiple others immunological defects have been reported, but not high levels of double negative T cells. Here we report a Brazilian patient with a novel phenotype of SFID syndrome, carrying multiple immune defects and harboring a novel mutation on TRNT1 gene.


Assuntos
Anemia Sideroblástica/diagnóstico , Anemia Sideroblástica/etiologia , Deficiências do Desenvolvimento/diagnóstico , Suscetibilidade a Doenças , Febre , Síndromes de Imunodeficiência/diagnóstico , Fenótipo , Alelos , Biópsia , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Linfócitos/imunologia , Linfócitos/metabolismo , Mutação
18.
Front Immunol ; 12: 672523, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968082

RESUMO

Lower respiratory infections are among the leading causes of morbidity and mortality worldwide. These potentially deadly infections are further exacerbated due to the growing incidence of antimicrobial resistance. To combat these infections there is a need to better understand immune mechanisms that promote microbial clearance. This need in the context of lung infections has been further heightened with the emergence of SARS-CoV-2. Group 3 innate lymphoid cells (ILC3s) are a recently discovered tissue resident innate immune cell found at mucosal sites that respond rapidly in the event of an infection. ILC3s have clear roles in regulating mucosal immunity and tissue homeostasis in the intestine, though the immunological functions in lungs remain unclear. It has been demonstrated in both viral and bacterial pneumonia that stimulated ILC3s secrete the cytokines IL-17 and IL-22 to promote both microbial clearance as well as tissue repair. In this review, we will evaluate regulation of ILC3s during inflammation and discuss recent studies that examine ILC3 function in the context of both bacterial and viral pulmonary infections.


Assuntos
COVID-19/imunologia , Imunidade nas Mucosas/imunologia , Linfócitos/imunologia , Pneumonia Bacteriana/imunologia , Mucosa Respiratória/imunologia , SARS-CoV-2/imunologia , Bactérias/imunologia , COVID-19/mortalidade , COVID-19/patologia , Imunidade Inata/imunologia , Inflamação/imunologia , Interleucina-17/metabolismo , Interleucinas/metabolismo , Pulmão/imunologia , Ativação Linfocitária/imunologia , Mucosa Respiratória/citologia
19.
Res Vet Sci ; 137: 274-280, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34058398

RESUMO

The local immunity of the lower urinary tract (LUT) is often presumed to influence the development of ascending infections and local inflammation. Due to small ruminants being at a higher risk of developing obstructive urolithiasis after early castration, a relationship is expected to exist between disturbed local immunity, castration and disease. However, the underlying pathophysiology and histological correlation of this assumption are unknown. This study examines the local cellular immunity of the LUT in male lambs with respect to castration status or a recent history of obstructive urolithiasis. Various tissue samples were taken and examined. The sample consisted of 34 male lambs, aged six months (n = 11 early and n = 11 late castration; n = 12 intact) and eight rams that had undergone necropsy due to fatal outcome after obstructive urolithiasis. Immunohistochemical stainings for CD3-T-cells, CD79α-B-cells and MAC 387-macrophages were performed and compared among the groups. Whereas no global group differences were evident, significant differences were found for the localizations (P = 0.002) with a significant interaction between group and localization (P = 0.004). The immunohistochemical results suggest that castration did not affect the cell number, but did have an effect on the distribution pattern of local T-cells within the urethra. In the urolithiasis cases, a reduction of CD3-positive cells along the middle part of the urethra was noticeable.


Assuntos
Linfócitos/imunologia , Macrófagos/imunologia , Orquiectomia/veterinária , Sistema Urinário/imunologia , Urolitíase/imunologia , Animais , Masculino , Ovinos , Doenças dos Ovinos , Uretra/imunologia , Urolitíase/veterinária
20.
Front Immunol ; 12: 672523, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1221949

RESUMO

Lower respiratory infections are among the leading causes of morbidity and mortality worldwide. These potentially deadly infections are further exacerbated due to the growing incidence of antimicrobial resistance. To combat these infections there is a need to better understand immune mechanisms that promote microbial clearance. This need in the context of lung infections has been further heightened with the emergence of SARS-CoV-2. Group 3 innate lymphoid cells (ILC3s) are a recently discovered tissue resident innate immune cell found at mucosal sites that respond rapidly in the event of an infection. ILC3s have clear roles in regulating mucosal immunity and tissue homeostasis in the intestine, though the immunological functions in lungs remain unclear. It has been demonstrated in both viral and bacterial pneumonia that stimulated ILC3s secrete the cytokines IL-17 and IL-22 to promote both microbial clearance as well as tissue repair. In this review, we will evaluate regulation of ILC3s during inflammation and discuss recent studies that examine ILC3 function in the context of both bacterial and viral pulmonary infections.


Assuntos
COVID-19/imunologia , Imunidade nas Mucosas/imunologia , Linfócitos/imunologia , Pneumonia Bacteriana/imunologia , Mucosa Respiratória/imunologia , SARS-CoV-2/imunologia , Bactérias/imunologia , COVID-19/mortalidade , COVID-19/patologia , Imunidade Inata/imunologia , Inflamação/imunologia , Interleucina-17/metabolismo , Interleucinas/metabolismo , Pulmão/imunologia , Ativação Linfocitária/imunologia , Mucosa Respiratória/citologia
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