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1.
Cells ; 9(10)2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003471

RESUMO

COVID-19, caused by SARS-CoV-2 virus, emerged as a pandemic disease posing a severe threat to global health. To date, sporadic studies have demonstrated that innate immune mechanisms, specifically neutrophilia, NETosis, and neutrophil-associated cytokine responses, are involved in COVID-19 pathogenesis; however, our understanding of the exact nature of this aspect of host-pathogen interaction is limited. Here, we present a detailed dissection of the features and functional profiles of neutrophils, dendritic cells, and monocytes in COVID-19. We portray the crucial role of neutrophils as drivers of hyperinflammation associated with COVID-19 disease via the shift towards their immature forms, enhanced degranulation, cytokine production, and augmented interferon responses. We demonstrate the impaired functionality of COVID-19 dendritic cells and monocytes, particularly their low expression of maturation markers, increased PD-L1 levels, and their inability to upregulate phenotype upon stimulation. In summary, our work highlights important data that prompt further research, as therapeutic targeting of neutrophils and their associated products may hold the potential to reduce the severity of COVID-19.


Assuntos
Infecções por Coronavirus/sangue , Células Dendríticas/imunologia , Monócitos/imunologia , Neutrófilos/imunologia , Pneumonia Viral/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Células Cultivadas , Infecções por Coronavirus/imunologia , Citocinas/genética , Citocinas/metabolismo , Feminino , Humanos , Imunidade Inata , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia
3.
Front Immunol ; 11: 2063, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013872

RESUMO

Background: Cases of excessive neutrophil counts in the blood in severe coronavirus disease (COVID-19) patients have drawn significant attention. Neutrophil infiltration was also noted on the pathological findings from autopsies. It is urgent to clarify the pathogenesis of neutrophils leading to severe pneumonia in COVID-19. Methods: A retrospective analysis was performed on 55 COVID-19 patients classified as mild (n = 22), moderate (n = 25), and severe (n = 8) according to the Guidelines released by the National Health Commission of China. Trends relating leukocyte counts and lungs examined by chest CT scan were quantified by Bayesian inference. Transcriptional signatures of host immune cells of four COVID19 patients were analyzed by RNA sequencing of lung specimens and BALF. Results: Neutrophilia occurred in 6 of 8 severe patients at 7-19 days after symptom onset, coinciding with lesion progression. Increasing neutrophil counts paralleled lesion CT values (slope: 0.8 and 0.3-1.2), reflecting neutrophilia-induced lung injury in severe patients. Transcriptome analysis revealed that neutrophil activation was correlated with 17 neutrophil extracellular trap (NET)-associated genes in COVID-19 patients, which was related to innate immunity and interacted with T/NK/B cells, as supported by a protein-protein interaction network analysis. Conclusion: Excessive neutrophils and associated NETs could explain the pathogenesis of lung injury in COVID-19 pneumonia.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Armadilhas Extracelulares/genética , Ativação de Neutrófilo/genética , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Adulto , Idoso , Teorema de Bayes , Infecções por Coronavirus/virologia , Feminino , Humanos , Contagem de Leucócitos , Lesão Pulmonar/imunologia , Lesão Pulmonar/patologia , Masculino , Pessoa de Meia-Idade , Infiltração de Neutrófilos/imunologia , Pandemias , Pneumonia Viral/virologia , Mapas de Interação de Proteínas/imunologia , RNA Viral/genética , Estudos Retrospectivos , Transcriptoma
4.
J Coll Physicians Surg Pak ; 30(9): 928-932, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33036676

RESUMO

OBJECTIVE: To investigate the association ​of white blood cell (WBC) counts, neutrophil, platelets, lymphocyte counts, C-reactive protein (CRP), neutrophil / lymphocyte ratio (NLR), derived NLR ratio (d-NLR), and platelet / lymphocyte ratio (PLR) at the time of first admission for mortality caused by COVID-19. STUDY DESIGN:  Descritive, analytical study. PLACE AND DURATION OF STUDY: Department of Emergency Medicine, Sakarya University Training and Research Hospital, Turkey from  March 2020 to  May 2020. METHODOLOGY: One hundred and sixty-nine patients with the diagnosis of Covid-19 were retrospectively reviewed. Patients were divided into two groups as survivors and non-survivors. Inclusion criteria were age ≥18 years, RT-PCR test positivity, hospitalisation. Patients with missing data were excluded. Data regarding age, gender, WBC counts, neutrophil, platelets, and lymphocyte, CRP, NLR, d-NLR, PLR and comorbid conditions were analysed for mortality. All tests were done with a two-sided significance of 5%. For each endpoint, the absolute and relative effects and their corresponding 95% confidence interval  were calculated. RESULTS: There was a statistically significant association between neutrophil, lymphocyte, CRP, NLR, d-NLR and PLR values (p=0.005, p<0.001, p<0.001, p<0.001, p<0.001, and p<0.001, respectively) with mortality status of the patients. The cutoff values calculated by this analysis were 67.50 years for age, 5.12 K / µl for neutrophil, 1.12 K / µl for lymphocyte, 67.78 mg / dl for CRP, 3.9 for NLR, 2.55 for d-NLR, and 148.85 for PLR. CONCLUSION: Altered neutrophil and lymphocyte counts, NLR, d-NLR, PLR, and CRP values can be used as early predictors of mortality in Covid-19 patients. Key Words: Covid-19, Mortality, Emergency, NLR, d-NLR, PLR.


Assuntos
Infecções por Coronavirus/mortalidade , Serviço Hospitalar de Emergência/estatística & dados numéricos , Pneumonia Viral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Proteína C-Reativa/análise , Infecções por Coronavirus/sangue , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pandemias , Contagem de Plaquetas , Pneumonia Viral/sangue
5.
Nat Commun ; 11(1): 4968, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009413

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a worldwide emergency. Early identification of patients at risk of progression may facilitate more individually aligned treatment plans and optimized utilization of medical resource. Here we conducted a multicenter retrospective study involving patients with moderate COVID-19 pneumonia to investigate the utility of chest computed tomography (CT) and clinical characteristics to risk-stratify the patients. Our results show that CT severity score is associated with inflammatory levels and that older age, higher neutrophil-to-lymphocyte ratio (NLR), and CT severity score on admission are independent risk factors for short-term progression. The nomogram based on these risk factors shows good calibration and discrimination in the derivation and validation cohorts. These findings have implications for predicting the progression risk of COVID-19 pneumonia patients at the time of admission. CT examination may help risk-stratification and guide the timing of admission.


Assuntos
Infecções por Coronavirus/diagnóstico , Progressão da Doença , Pneumonia Viral/diagnóstico , Pneumonia , Tomografia Computadorizada por Raios X/métodos , Adulto , Betacoronavirus , China , Técnicas de Laboratório Clínico , Coinfecção , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Feminino , Hospitalização , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Análise de Regressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
6.
Epidemiol Infect ; 148: e211, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32900409

RESUMO

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern. The current study aims to explore whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with the development of death in patients with COVID-19. A total of 131 patients diagnosed with COVID-19 from 13 February 2020 to 14 March 2020 in a hospital in Wuhan designated for treating COVID-19 were enrolled in the current study. These 131 patients had a median age of 64 years old (interquartile range: 56-71 years old). Furthermore, among these patients, 111 (91.8%) patients were discharged and 12 (9.2%) patients died in the hospital. The pooled analysis revealed that the NLR at admission was significantly elevated for non-survivors, when compared to survivors (P < 0.001). The NLR of 3.338 was associated with all-cause mortality, with a sensitivity of 100.0% and a specificity of 84.0% (area under the curve (AUC): 0.963, 95% confidence interval (CI) 0.911-1.000; P < 0.001). In view of the small number of deaths (n = 12) in the current study, NLR of 2.306 might have potential value for helping clinicians to identify patients with severe COVID-19, with a sensitivity of 100.0% and a specificity of 56.7% (AUC: 0.729, 95% CI 0.563-0.892; P = 0.063). The NLR was significantly associated with the development of death in patients with COVID-19. Hence, NLR is a useful biomarker to predict the all-cause mortality of COVID-19.


Assuntos
Betacoronavirus , Plaquetas , Infecções por Coronavirus/mortalidade , Linfócitos , Neutrófilos , Pneumonia Viral/mortalidade , Adolescente , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Criança , Pré-Escolar , Infecções por Coronavirus/sangue , Infecções por Coronavirus/etiologia , Humanos , Lactente , Recém-Nascido , Pacientes Internados , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/etiologia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
7.
Rev Assoc Med Bras (1992) ; 66Suppl 2(Suppl 2): 77-81, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32965361

RESUMO

BACKGROUND: Coronavirus Disease 2019 is an acute inflammatory respiratory disease. It causes many changes in hemogram parameters. Low albumin levels are associated with mortality risk in hospitalized patients. The aim of the present study is to reveal the place of neutrophil count to albumin ratio in predicting mortality in patients with COVID-19. METHODS: 144 patients, 65 females and 79 males, were included in the study. Patients were divided into 2 groups. Group 1 was the non-severe group (n:85), and Group 2 was severe (n:59). Demographic data, neutrophil, lymphocyte and platelet counts, albumin and C-reactive protein (CRP) levels were recorded. Neutrophil count to albumin ratio (NAR) was calculated by dividing the absolute neutrophil counts by the albumin levels. The NAR and levels of the two groups were then compared. RESULTS: There were no significant differences in gender and platelet count (201 vs. 211 K/mL) between the groups (p>0,05). Ages (62.0 ± 14.3 vs 68.6 ± 12.2 years), albumin (33.1 vs 29.9 gr/L), CRP (33 vs 113 mg/l), neutrophil count (4 vs 7.24 K/mL), WBC counts (6.70 vs 8.50 K/mL), NAR values (113.5 vs 267.2) and number of Death (5 vs 33) were found to be statistically higher (p <0.001) in Group 2 than in Group 1. The NAR value of 201.5 showed mortality in all patients with COVID-19 to have 71.1% sensitivity and 71.7% specificity (AUC:0.736, 95% CI: 0.641-0.832, p<0.001). CONCLUSION: The present study showed that NAR levels can be a cheap and simple marker for predicting mortality in patients with COVID-19.


Assuntos
Albuminas , Infecções por Coronavirus/epidemiologia , Neutrófilos , Pandemias , Pneumonia Viral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Curva ROC , Estudos Retrospectivos
8.
Nat Commun ; 11(1): 4387, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873795

RESUMO

The role of neutrophils in solid tumor metastasis remains largely controversial. In preclinical models of solid tumors, both pro-metastatic and anti-metastatic effects of neutrophils have been reported. In this study, using mouse models of breast cancer, we demonstrate that the metastasis-modulating effects of neutrophils are dictated by the status of host natural killer (NK) cells. In NK cell-deficient mice, granulocyte colony-stimulating factor-expanded neutrophils show an inhibitory effect on the metastatic colonization of breast tumor cells in the lung. In contrast, in NK cell-competent mice, neutrophils facilitate metastatic colonization in the same tumor models. In an ex vivo neutrophil-NK cell-tumor cell tri-cell co-culture system, neutrophils are shown to potentially suppress the tumoricidal activity of NK cells, while neutrophils themselves are tumoricidal. Intriguingly, these two modulatory effects by neutrophils are both mediated by reactive oxygen species. Collectively, the absence or presence of NK cells, governs the net tumor-modulatory effects of neutrophils.


Assuntos
Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Mamárias Animais/imunologia , Neutropenia/prevenção & controle , Neutrófilos/imunologia , Animais , Linhagem Celular Tumoral/transplante , Técnicas de Cocultura , Modelos Animais de Doenças , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Injeções Intravenosas , Pulmão/citologia , Pulmão/imunologia , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/secundário , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/imunologia , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Animais/sangue , Neoplasias Mamárias Animais/complicações , Neoplasias Mamárias Animais/patologia , Camundongos , Camundongos Endogâmicos NOD , Neutropenia/sangue , Neutropenia/etiologia , Neutropenia/imunologia , Neutrófilos/efeitos dos fármacos , Cultura Primária de Células
9.
J Transl Med ; 18(1): 354, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933530

RESUMO

BACKGROUND: Severe COVID-19 infection results in a systemic inflammatory response (SIRS). This SIRS response shares similarities to the changes observed during the peri-operative period that are recognised to be associated with the development of multiple organ failure. METHODS: Electronic patient records for patients who were admitted to an urban teaching hospital during the initial 7-week period of the COVID-19 pandemic in Glasgow, U.K. (17th March 2020-1st May 2020) were examined for routine clinical, laboratory and clinical outcome data. Age, sex, BMI and documented evidence of COVID-19 infection at time of discharge or death certification were considered minimal criteria for inclusion. RESULTS: Of the 224 patients who fulfilled the criteria for inclusion, 52 (23%) had died at 30-days following admission. COVID-19 related respiratory failure (75%) and multiorgan failure (12%) were the commonest causes of death recorded. Age ≥ 70 years (p < 0.001), past medical history of cognitive impairment (p ≤ 0.001), previous delirium (p < 0.001), clinical frailty score > 3 (p < 0.001), hypertension (p < 0.05), heart failure (p < 0.01), national early warning score (NEWS) > 4 (p < 0.01), positive CXR (p < 0.01), and subsequent positive COVID-19 swab (p ≤ 0.001) were associated with 30-day mortality. CRP > 80 mg/L (p < 0.05), albumin < 35 g/L (p < 0.05), peri-operative Glasgow Prognostic Score (poGPS) (p < 0.05), lymphocytes < 1.5 109/l (p < 0.05), neutrophil lymphocyte ratio (p ≤ 0.001), haematocrit (< 0.40 L/L (male)/ < 0.37 L/L (female)) (p ≤ 0.01), urea > 7.5 mmol/L (p < 0.001), creatinine > 130 mmol/L (p < 0.05) and elevated urea: albumin ratio (< 0.001) were also associated with 30-day mortality. On multivariate analysis, age ≥ 70 years (O.R. 3.9, 95% C.I. 1.4-8.2, p < 0.001), past medical history of heart failure (O.R. 3.3, 95% C.I. 1.2-19.3, p < 0.05), NEWS > 4 (O.R. 2.4, 95% C.I. 1.1-4.4, p < 0.05), positive initial CXR (O.R. 0.4, 95% C.I. 0.2-0.9, p < 0.05) and poGPS (O.R. 2.3, 95% C.I. 1.1-4.4, p < 0.05) remained independently associated with 30-day mortality. Among those patients who tested PCR COVID-19 positive (n = 122), age ≥ 70 years (O.R. 4.7, 95% C.I. 2.0-11.3, p < 0.001), past medical history of heart failure (O.R. 4.4, 95% C.I. 1.2-20.5, p < 0.05) and poGPS (O.R. 2.4, 95% C.I. 1.1-5.1, p < 0.05) remained independently associated with 30-days mortality. CONCLUSION: Age ≥ 70 years and severe systemic inflammation as measured by the peri-operative Glasgow Prognostic Score are independently associated with 30-day mortality among patients admitted to hospital with COVID-19 infection.


Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Feminino , Mortalidade Hospitalar , Hospitalização , Hospitais de Ensino , Hospitais Urbanos , Humanos , Inflamação/fisiopatologia , Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neutrófilos , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Prognóstico , Escócia/epidemiologia , Pesquisa Médica Translacional
10.
Nat Commun ; 11(1): 4697, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943639

RESUMO

Unassisted metastasis through the lymphatic system is a mechanism of dissemination thus far ascribed only to cancer cells. Here, we report that Streptococcus pyogenes also hijack lymphatic vessels to escape a local infection site, transiting through sequential lymph nodes and efferent lymphatic vessels to enter the bloodstream. Contrasting with previously reported mechanisms of intracellular pathogen carriage by phagocytes, we show S. pyogenes remain extracellular during transit, first in afferent and then efferent lymphatics that carry the bacteria through successive draining lymph nodes. We identify streptococcal virulence mechanisms important for bacterial lymphatic dissemination and show that metastatic streptococci within infected lymph nodes resist and subvert clearance by phagocytes, enabling replication that can seed intense bloodstream infection. The findings establish the lymphatic system as both a survival niche and conduit to the bloodstream for S. pyogenes, explaining the phenomenon of occult bacteraemia. This work provides new perspectives in streptococcal pathogenesis with implications for immunity.


Assuntos
Linfonodos/microbiologia , Metástase Linfática , Vasos Linfáticos/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/patogenicidade , Animais , Bacteriemia/microbiologia , Bacteriemia/patologia , Modelos Animais de Doenças , Feminino , Interleucina-8/metabolismo , Linfonodos/imunologia , Linfonodos/patologia , Metástase Linfática/patologia , Sistema Linfático , Vasos Linfáticos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neutrófilos/microbiologia , Fagocitose , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/patologia , Streptococcus pyogenes/genética , Virulência
11.
BMJ Open ; 10(9): e041983, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967887

RESUMO

OBJECTIVES: Being able to predict which patients with COVID-19 are going to deteriorate is important to help identify patients for clinical and research practice. Clinical prediction models play a critical role in this process, but current models are of limited value because they are typically restricted to baseline predictors and do not always use contemporary statistical methods. We sought to explore the benefits of incorporating dynamic changes in routinely measured biomarkers, non-linear effects and applying 'state-of-the-art' statistical methods in the development of a prognostic model to predict death in hospitalised patients with COVID-19. DESIGN: The data were analysed from admissions with COVID-19 to three hospital sites. Exploratory data analysis included a graphical approach to partial correlations. Dynamic biomarkers were considered up to 5 days following admission rather than depending solely on baseline or single time-point data. Marked departures from linear effects of covariates were identified by employing smoothing splines within a generalised additive modelling framework. SETTING: 3 secondary and tertiary level centres in Greater Manchester, the UK. PARTICIPANTS: 392 hospitalised patients with a diagnosis of COVID-19. RESULTS: 392 patients with a COVID-19 diagnosis were identified. Area under the receiver operating characteristic curve increased from 0.73 using admission data alone to 0.75 when also considering results of baseline blood samples and to 0.83 when considering dynamic values of routinely collected markers. There was clear non-linearity in the association of age with patient outcome. CONCLUSIONS: This study shows that clinical prediction models to predict death in hospitalised patients with COVID-19 can be improved by taking into account both non-linear effects in covariates such as age and dynamic changes in values of biomarkers.


Assuntos
Bilirrubina/sangue , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/mortalidade , Creatinina/sangue , Contagem de Linfócitos , Neutrófilos , Pneumonia Viral/mortalidade , Ureia/sangue , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Betacoronavirus , Biomarcadores/sangue , Estudos de Coortes , Infecções por Coronavirus/sangue , Feminino , Hospitalização , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco , Reino Unido
12.
Bratisl Lek Listy ; 121(7): 466-470, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32989997

RESUMO

Coronavirus disease is caused by a virus that is the cause of a potentially fatal disease worldwide. Coronavirus is a pathogen that primarily affects the human respiratory system. Coronavirus 2019 (COVID-19) has been named WHO since February 11, 2020. The first cases of COVID-19 were reported in December 2019. In January 2020, COVID-19 infection was identified in hospitalized patients in Wuhan, China. We analyze the role of neutrophil-lymphocyte ratio (NLR) in viral infection with special emphasize on novel corona virus disease-COVID-19. NLR may be used for early detection and may reflect progression to the more severe illness leading to SARS-CoV-2. In the mini review we investigate the use of NLR as a surrogate marker for diagnosis and stratification of COVID-19.Clinical symptoms such as pneumonia, acute respiratory distress syndrome, acute heart damage have led to death. In some cases, multiple inflammations have been observed. Treatment with interferon inhalation showed no clinical effect and the condition worsened instead (Tab. 5, Fig. 1, Ref. 18). Keywords: neutrophil-to-lymphocyte ratio, corona virus SARS-CoV-2, COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , China , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Diagnóstico Precoce , Humanos , Linfócitos , Neutrófilos , Pneumonia Viral/diagnóstico
13.
Medicine (Baltimore) ; 99(33): e21550, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872002

RESUMO

To study the relationship between neutrophil to lymphocyte ratio (NLR) and exercise tolerance of patients with chronic obstructive pulmonary disease (COPD).235 patients with COPD were selected as the study subjects. Complete blood count, C reactive protein (CRP), pulmonary function tests, the 6-minute walk distance (6MWD), Modified Medical Respiratory Council, the COPD assessment test, and clinical COPD questionnaire were tested. Heart rate, oxygen saturation, and Borg scale were tested before or after 6MWD test.By the median of NLR, the subjects were divided into 2 groups, NLR ≥4.5 group and NLR <4.5 group. The white blood cell count (WBC), CRP and deoxygenation saturation in the NLR ≥4.5 group were higher than those in the NLR <4.5 group, while the age, body mass index (BMI), 6MWD, and heart rate variation were lower than those in the NLR <4.5 group. CRP, WBC, and deoxygenation saturation had positive effects on NLR, BMI, 6MWT, and heart rate variation had negative effects on NLR. The Pearson correlation analysis showed NLR was positively correlated with WBC, CRP, BMI index, 6MWT, and deoxygenation saturation, while it was negatively correlated with BMI and heart rate variation.NLR might associate with exercise tolerance and cardiorespiratory reserve of COPD patients, and could be used as an indicator of muscle function in COPD patients.


Assuntos
Tolerância ao Exercício , Linfócitos/metabolismo , Neutrófilos/metabolismo , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Inquéritos e Questionários , Teste de Caminhada
15.
PLoS Pathog ; 16(9): e1008854, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32956405

RESUMO

Aspergillus fumigatus is an opportunistic fungal pathogen of immunocompromised patient populations. Mortality is thought to be context-specific and occurs via both enhanced fungal growth and immunopathogenesis. NLRX1 is a negative regulator of immune signaling and metabolic pathways implicated in host responses to microbes, cancers, and autoimmune diseases. Our study indicates loss of Nlrx1 results in enhanced fungal burden, pulmonary inflammation, immune cell recruitment, and mortality across immuno-suppressed and immuno-competent models of IPA using two clinically derived isolates (AF293, CEA10). We observed that the heightened mortality is due to enhanced recruitment of CD103+ dendritic cells (DCs) that produce elevated amounts of IL-4 resulting in a detrimental Th2-mediated immune response. Adoptive transfer of Nlrx1-/- CD103+ DCs in neutropenic NRG mice results in enhanced mortality that can be ablated using IL-4 neutralizing antibodies. In vitro analysis of CD103+ DCs indicates loss of Nlrx1 results in enhanced IL-4 production via elevated activation of the JNK/JunB pathways. Interestingly, loss of Nlrx1 also results in enhanced recruitment of monocytes and neutrophils. Chimeras of irradiated Nlrx1-/- mice reconstituted with wild type bone marrow have enhanced neutrophil recruitment and survival during models of IPA. This enhanced immune cell recruitment in the absence of Nlrx1 is mediated by excessive production of CXCL8/IL-8 family of chemokines and IL-6 via early and enhanced activation of P38 in response to A. fumigatus conidia as shown in BEAS-2B airway epithelial cells. In summary, our results point strongly towards the cell-specific and contextual function of Nlrx1 during invasive pulmonary aspergillosis and may lead to novel therapeutics to reduce Th2 responses by CD103+ DCs or heightened recruitment of neutrophils.


Assuntos
Aspergillus fumigatus/imunologia , Células Dendríticas/imunologia , Sistema de Sinalização das MAP Quinases/imunologia , Proteínas Mitocondriais/imunologia , Aspergilose Pulmonar/imunologia , Células Th2/imunologia , Animais , Linhagem Celular , Citocinas/genética , Citocinas/imunologia , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/imunologia , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Camundongos Knockout , Proteínas Mitocondriais/genética , Neutrófilos/imunologia , Neutrófilos/patologia , Aspergilose Pulmonar/genética , Aspergilose Pulmonar/patologia , Células Th2/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia
16.
Sci Rep ; 10(1): 15838, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985562

RESUMO

The coronavirus disease 2019 (COVID-19) has been spreading worldwide. Severe cases quickly progressed with unfavorable outcomes. We aim to investigate the clinical features of COVID-19 and identify the risk factors associated with its progression. Data of confirmed SARS-CoV-2-infected patients and healthy participants were collected. Thirty-seven healthy people and 79 confirmed patients, which include 48 severe patients and 31 mild patients, were recruited. COVID-19 patients presented with dysregulated immune response (decreased T, B, and NK cells and increased inflammatory cytokines). Also, they were found to have increased levels of white blood cell, neutrophil count, and D-dimer in severe cases. Moreover, lymphocyte, CD4+ T cell, CD8+ T cell, NK cell, and B cell counts were lower in the severe group. Multivariate logistic regression analysis showed that CD4+ cell count, neutrophil-to-lymphocyte ratio (NLR) and D-dimer were risk factors for severe cases. Both CT score and clinical pulmonary infection score (CPIS) were associated with disease severity. The receiver operating characteristic (ROC) curve analysis has shown that all these parameters and scores had quite a high predictive value. Immune dysfunction plays critical roles in disease progression. Early and constant surveillance of complete blood cell count, T lymphocyte subsets, coagulation function, CT scan and CPIS was recommended for early screening of severe cases.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Fenômenos do Sistema Imunológico/fisiologia , Pneumonia Viral/imunologia , Adulto , Idoso , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/patologia , Feminino , Humanos , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Pandemias , Pneumonia Viral/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Front Immunol ; 11: 2075, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983157

RESUMO

To explore the metabolic changes and immune profiles in patients with COVID-19, we analyzed the data of patients with mild and severe COVID-19 as well as young children with COVID-19. Of the leukocytes, 47% (IQR, 33-59) were lymphocytes [2.5 × 109/L (IQR, 2.2-3.3)], and monocytes were 0.51 × 109/L (IQR, 0.45-0.57) in young children with COVID-19. In 32 mild COVID-19 patients, circulating monocytes were 0.45 × 109/L (IQR, 0.36-0.64). Twenty-one severe patients had low PO2 [57 mmHg (IQR, 50-73)] and SO2 [90% (IQR, 86-93)] and high lactate dehydrogenase [580 U/L (IQR, 447-696)], cardiac troponin I [0.07 ng/mL (IQR, 0.02-0.30)], and pro-BNP [498 pg/mL (IQR, 241-1,726)]. Serum D-dimer and FDP were 9.89 mg/L (IQR, 3.62-22.85) and 32.7 mg/L (IQR, 12.8-81.9), and a large number of RBC (46/µL (IQR, 4-242) was presented in urine, a cue of disseminated intravascular coagulation (DIC) in severe patients. Three patients had comorbidity with diabetes, and 18 patients without diabetes also presented high blood glucose [7.4 mmol/L (IQR, 5.9-10.1)]. Fifteen of 21 (71%) severe cases had urine glucose +, and nine of 21 (43%) had urine ketone body +. The increased glucose was partially caused by reduced glucose consumption of cells. Severe cases had extraordinarily low serum uric acid [176 µmol/L (IQR, 131-256)]. In the late stage of COVID-19, severe cases had extremely low CD4+ T cells and CD8+ T cells, but unusually high neutrophils [6.5 × 109/L (IQR, 4.8-9.6)], procalcitonin [0.27 ng/mL (IQR, 0.14-1.94)], C-reactive protein [66 mg/L (IQR, 25-114)] and an extremely high level of interleukin-6. Four of 21 (19%) severe cases had co-infection with fungi, and two of 21 (9%) severe cases had bacterial infection. Our findings suggest that, severe cases had acute respiratory distress syndrome (ARDS) I-III, and metabolic disorders of glucose, lipid, uric acid, etc., even multiple organ dysfunction (MODS) and DIC. Increased neutrophils and severe inflammatory responses were involved in ARDS, MODS, and DIC. With the dramatical decrease of T-lymphocytes, severe cases were susceptible to co-infect with bacteria and fungi in the late stage of COVID-19. In young children, extremely high lymphocytes and monocytes might be associated with the low morbidity of COVID-19. The significantly increased monocytes might play an important role in the recovery of patients with mild COVID-19.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Adulto , Idoso , Glicemia/análise , Proteína C-Reativa/análise , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Criança , Pré-Escolar , Infecções por Coronavirus/virologia , Feminino , Humanos , Interleucina-6/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Pandemias , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ácido Úrico/sangue
18.
Front Immunol ; 11: 2145, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983174

RESUMO

SARS-CoV-2 infection has recently been declared a pandemic. Some patients showing severe symptoms exhibit drastic inflammation and airway damage. In this study, we re-analyzed published scRNA-seq data of COVID-19 patient bronchoalveolar lavage fluid to further classify and compare immunological features according to the patient's disease severity. Patients with severe symptoms showed DNA damage and apoptotic features of epithelial cells. Our results suggested that epithelial damage was associated with neutrophil infiltration. Myeloid cells of severe patients showed higher expression of proinflammatory cytokines and chemokines such as CXCL8. As a result, neutrophils were abundant in lungs of patients from the severe group. Furthermore, recruited neutrophils highly expressed genes related to neutrophil extracellular traps. Neutrophil-mediated inflammation was regulated by glucocorticoid receptor expression and activity. Based on these results, we suggest that severe COVID-19 symptoms may be determined by differential expression of glucocorticoid receptors and neutrophils.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Interleucina-8/genética , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Receptores de Glucocorticoides/genética , Índice de Gravidade de Doença , Transcriptoma , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/imunologia , Infecções por Coronavirus/virologia , Células Epiteliais/patologia , Armadilhas Extracelulares/imunologia , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Inflamação/imunologia , Interleucina-8/metabolismo , Masculino , Pessoa de Meia-Idade , Células Mieloides/imunologia , Infiltração de Neutrófilos/imunologia , Pandemias , Pneumonia Viral/virologia , RNA-Seq , Receptores de Glucocorticoides/metabolismo , Análise de Célula Única/métodos
19.
Front Immunol ; 11: 2160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983180

RESUMO

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is spreading worldwide. Measuring the prevention and control of the disease has become a matter requiring urgent focus. Objective: Based on coronavirus disease 2019 (COVID-19) clinical data from Wuhan, we conducted an in-depth analysis to clarify some of the pathological mechanisms of the disease and identify simple measures to predict its severity early on. Methods: A total of 230 patients with non-mild COVID-19 were recruited, and information on their clinical characteristics, inflammatory cytokines, and T lymphocyte subsets was collected. Risk factors for severity were analyzed by binary logistic regression, and the associations of neutrophil-to-lymphocyte ratios (N/LRs) with illness severity, disease course, CT grading, inflammatory cytokines, and T lymphocyte subsets were evaluated. Results: Our results showed that the N/LRs were closely related to interleukin (IL)-6 and IL-10 (P < 0.001, P = 0.024) and to CD3+ and CD8+ T lymphocytes (P < 0.001, P = 0.046). In particular, the N/LRs were positively correlated with the severity and course of the disease (P = 0.021, P < 0.001). Compared to the values at the first test after admission, IL-6 and IL-10 were significantly decreased and increased, respectively, as of the last test before discharge (P = 0.006, P < 0.001). More importantly, through binary logistic regression, we found that male sex, underlying diseases (such as cardiovascular disease), pulse, and N/LRs were all closely related to the severity of the disease (P = 0.004, P = 0.012, P = 0.013, P = 0.028). Conclusions: As a quick and convenient marker of inflammation, N/LRs may predict the disease course and severity level of non-mild COVID-19; male sex, cardiovascular disease, and pulse are also risk factors for the severity of non-mild COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Índice de Gravidade de Doença , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Biomarcadores , Doenças Cardiovasculares , Infecções por Coronavirus/virologia , Feminino , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Pulso Arterial , Fatores de Risco , Fatores Sexuais
20.
Sci Rep ; 10(1): 15058, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929124

RESUMO

Coronavirus disease 2019 (COVID-19) is an important and urgent threat to global health. Inflammation factors are important for COVID-19 mortality, and we aim to explore whether the baseline levels of procalcitonin (PCT), C-reaction protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) are associated with an increased risk of mortality in patients with COVID-19. A retrospective study was conducted and a total of 76 patients with confirmed COVID-19 were included between January 17, 2020 to March 2, 2020, of these cases, 17 patients were dead. After adjusting covariates, PCT (≥ 0.10 ng/mL) and CRP (≥ 52.14 mg/L) exhibited independent increasing risks of mortality were used hazard ratio (HR) of 52.68 (95% confidence interval [CI]: 1.77-1571.66) and 5.47 (95% CI: 1.04-28.72), respectively. However, NRL (≥ 3.59) was not found to be an independent risk factor for death in our study. Furthermore, the elevated PCT levels were still associated with increasing risk of mortality in the old age group (age ≥ 60 y), and in the critically severe and severe patients after adjustment for complications. Thu Baseline levels of PCT and CRP have been addressed as independent predictors of mortality in patients with COVID-19.


Assuntos
Proteína C-Reativa/análise , Infecções por Coronavirus/diagnóstico , Linfócitos/citologia , Neutrófilos/citologia , Pneumonia Viral/diagnóstico , Pró-Calcitonina/análise , Adolescente , Adulto , Idoso , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , China , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
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