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1.
Sci Rep ; 11(1): 21519, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500511

ABSTRACT

A high neutrophil to lymphocyte ratio (NLR) is considered an unfavorable prognostic factor in various diseases, including COVID-19. The prognostic value of NLR in other respiratory viral infections, such as Influenza, has not hitherto been extensively studied. We aimed to compare the prognostic value of NLR in COVID-19, Influenza and Respiratory Syncytial Virus infection (RSV). A retrospective cohort of COVID-19, Influenza and RSV patients admitted to the Tel Aviv Medical Center from January 2010 to October 2020 was analyzed. Laboratory, demographic, and clinical parameters were collected. Two way analyses of variance (ANOVA) was used to compare the association between NLR values and poor outcomes among the three groups. ROC curve analyses for each virus was applied to test the discrimination ability of NLR. 722 COVID-19, 2213 influenza and 482 RSV patients were included. Above the age of 50, NLR at admission was significantly lower among COVID-19 patients (P < 0.001). NLR was associated with poor clinical outcome only in the COVID-19 group. ROC curve analysis was performed; the area under curve of poor outcomes for COVID-19 was 0.68, compared with 0.57 and 0.58 for Influenza and RSV respectively. In the COVID-19 group, multivariate logistic regression identified a high NLR (defined as a value above 6.82) to be a prognostic factor for poor clinical outcome, after adjusting for age, sex and Charlson comorbidity score (odds ratio of 2.9, P < 0.001). NLR at admission is lower and has more prognostic value in COVID-19 patients, when compared to Influenza and RSV.


Subject(s)
COVID-19/pathology , Influenza, Human/pathology , Respiratory Syncytial Virus Infections/pathology , Adult , Aged , Aged, 80 and over , Area Under Curve , COVID-19/immunology , COVID-19/virology , Female , Humans , Influenza, Human/immunology , Lymphocytes/cytology , Lymphocytes/metabolism , Male , Middle Aged , Neutrophils/cytology , Neutrophils/metabolism , Prognosis , ROC Curve , Respiratory Syncytial Virus Infections/immunology , Retrospective Studies , SARS-CoV-2/isolation & purification
2.
J Am Soc Nephrol ; 32(1): 69-85, 2021 01.
Article in English | MEDLINE | ID: covidwho-1496661

ABSTRACT

BACKGROUND: In children, the acute pyelonephritis that can result from urinary tract infections (UTIs), which commonly ascend from the bladder to the kidney, is a growing concern because it poses a risk of renal scarring and irreversible loss of kidney function. To date, the cellular mechanisms underlying acute pyelonephritis-driven renal scarring remain unknown. METHODS: We used a preclinical model of uropathogenic Escherichia coli-induced acute pyelonephritis to determine the contribution of neutrophils and monocytes to resolution of the condition and the subsequent development of kidney fibrosis. We used cell-specific monoclonal antibodies to eliminate neutrophils, monocytes, or both. Bacterial ascent and the cell dynamics of phagocytic cells were assessed by biophotonic imaging and flow cytometry, respectively. We used quantitative RT-PCR and histopathologic analyses to evaluate inflammation and renal scarring. RESULTS: We found that neutrophils are critical to control bacterial ascent, which is in line with previous studies suggesting a protective role for neutrophils during a UTI, whereas monocyte-derived macrophages orchestrate a strong, but ineffective, inflammatory response against uropathogenic, E. coli-induced, acute pyelonephritis. Experimental neutropenia during acute pyelonephritis resulted in a compensatory increase in the number of monocytes and heightened macrophage-dependent inflammation in the kidney. Exacerbated macrophage-mediated inflammatory responses promoted renal scarring and compromised renal function, as indicated by elevated serum creatinine, BUN, and potassium. CONCLUSIONS: These findings reveal a previously unappreciated outcome for neutrophil-macrophage imbalance in promoting host susceptibility to acute pyelonephritis and the development of permanent renal damage. This suggests targeting dysregulated macrophage responses might be a therapeutic tool to prevent renal scarring during acute pyelonephritis.


Subject(s)
Cicatrix/physiopathology , Kidney/physiopathology , Macrophages/cytology , Neutrophils/cytology , Pyelonephritis/metabolism , Animals , Escherichia coli , Female , Fibrosis/microbiology , Fibrosis/physiopathology , Inflammation , Kidney/microbiology , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Neutrophils/metabolism , Phagocytosis , Pyelonephritis/microbiology , Pyelonephritis/physiopathology , Urinary Tract Infections/microbiology , Urinary Tract Infections/physiopathology
3.
Front Immunol ; 12: 744799, 2021.
Article in English | MEDLINE | ID: covidwho-1448731

ABSTRACT

Sepsis is a global health emergency, which is caused by various sources of infection that lead to changes in gene expression, protein-coding, and metabolism. Advancements in "omics" technologies have provided valuable tools to unravel the mechanisms involved in the pathogenesis of this disease. In this study, we performed shotgun mass spectrometry in peripheral blood mononuclear cells (PBMC) from septic patients (N=24) and healthy controls (N=9) and combined these results with two public microarray leukocytes datasets. Through combination of transcriptome and proteome profiling, we identified 170 co-differentially expressed genes/proteins. Among these, 122 genes/proteins displayed the same expression trend. Ingenuity Pathway Analysis revealed pathways related to lymphocyte functions with decreased status, and defense processes that were predicted to be strongly increased. Protein-protein interaction network analyses revealed two densely connected regions, which mainly included down-regulated genes/proteins that were related to the transcription of RNA, translation of proteins, and mitochondrial translation. Additionally, we identified one module comprising of up-regulated genes/proteins, which were mainly related to low-density neutrophils (LDNs). LDNs were reported in sepsis and in COVID-19. Changes in gene expression level were validated using quantitative real-time PCR in PBMCs from patients with sepsis. To further support that the source of the upregulated module of genes/proteins found in our results were derived from LDNs, we identified an increase of this population by flow cytometry in PBMC samples obtained from the same cohort of septic patients included in the proteomic analysis. This study provides new insights into a reprioritization of biological functions in response to sepsis that involved a transcriptional and translational shutdown of genes/proteins, with exception of a set of genes/proteins related to LDNs and host-defense system.


Subject(s)
Leukocytes, Mononuclear/metabolism , Neutrophils/metabolism , Sepsis/metabolism , Databases, Factual , Gene Expression Profiling , Gene Expression Regulation , Humans , Leukocytes, Mononuclear/cytology , Myeloid-Derived Suppressor Cells/cytology , Myeloid-Derived Suppressor Cells/metabolism , Neutrophils/cytology , Protein Interaction Maps , Proteomics , Sepsis/genetics , Sepsis/immunology
4.
Cells ; 10(10)2021 09 26.
Article in English | MEDLINE | ID: covidwho-1438528

ABSTRACT

The coronavirus disease 2019 (COVID-19) is related to enhanced production of NETs, and autoimmune/autoinflammatory phenomena. We evaluated the proportion of low-density granulocytes (LDG) by flow cytometry, and their capacity to produce NETs was compared with that of conventional neutrophils. NETs and their protein cargo were quantified by confocal microscopy and ELISA. Antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and the degradation capacity of NETs were addressed in serum. MILLIPLEX assay was used to assess the cytokine levels in macrophages' supernatant and serum. We found a higher proportion of LDG in severe and critical COVID-19 which correlated with severity and inflammatory markers. Severe/critical COVID-19 patients had higher plasmatic NE, LL-37 and HMGB1-DNA complexes, whilst ISG-15-DNA complexes were lower in severe patients. Sera from severe/critical COVID-19 patients had lower degradation capacity of NETs, which was reverted after adding hrDNase. Anti-NET antibodies were found in COVID-19, which correlated with ANA and ANCA positivity. NET stimuli enhanced the secretion of cytokines in macrophages. This study unveils the role of COVID-19 NETs as inducers of pro-inflammatory and autoimmune responses. The deficient degradation capacity of NETs may contribute to the accumulation of these structures and anti-NET antibodies are related to the presence of autoantibodies.


Subject(s)
Autoimmunity , COVID-19/blood , COVID-19/immunology , Extracellular Traps/immunology , Immunity, Humoral , Inflammation , Neutrophils/immunology , Antibodies, Antinuclear , Antimicrobial Cationic Peptides/blood , Autoantibodies/metabolism , Cross-Sectional Studies , Cytokines/metabolism , Cytokines/pharmacology , Flow Cytometry , Granulocytes/metabolism , HMGB1 Protein/blood , Healthy Volunteers , Humans , Microscopy, Confocal , Monocytes/cytology , Neutrophils/cytology , SARS-CoV-2 , Ubiquitins/pharmacology
5.
BMC Infect Dis ; 21(1): 760, 2021 Aug 05.
Article in English | MEDLINE | ID: covidwho-1403220

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread around the world. This retrospective study aims to analyze the clinical features of COVID-19 patients with cancer and identify death outcome related risk factors. METHODS: From February 10th to April 15th, 2020, 103 COVID-19 patients with cancer were enrolled. Difference analyses were performed between severe and non-severe patients. A propensity score matching (PSM) analysis was performed, including 103 COVID-19 patients with cancer and 206 matched non-cancer COVID-19 patients. Next, we identified death related risk factors and developed a nomogram for predicting the probability. RESULTS: In 103 COVID-19 patients with cancer, the main cancer categories were breast cancer, lung cancer and bladder cancer. Compared to non-severe patients, severe patients had a higher median age, and a higher proportion of smokers, diabetes, heart disease and dyspnea. In addition, most of the laboratory results between two groups were significantly different. PSM analysis found that the proportion of dyspnea was much higher in COVID-19 patients with cancer. The severity incidence in two groups were similar, while a much higher mortality was found in COVID-19 patients with cancer compared to that in COVID-19 patients without cancer (11.7% vs. 4.4%, P = 0.028). Furthermore, we found that neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were related to death outcome. And a nomogram based on the factors was developed. CONCLUSION: In COVID-19 patients with cancer, the clinical features and laboratory results between severe group and non-severe group were significantly different. NLR and CRP were the risk factors that could predict death outcome.


Subject(s)
COVID-19 , Neoplasms , Adult , Aged , Aged, 80 and over , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/mortality , Female , Humans , Lymphocytes/cytology , Male , Middle Aged , Neoplasms/complications , Neoplasms/mortality , Neutrophils/cytology , Nomograms , Retrospective Studies , Risk Factors , Young Adult
6.
FASEB J ; 35(10): e21843, 2021 10.
Article in English | MEDLINE | ID: covidwho-1378886

ABSTRACT

Robust inflammatory responses are critical to survival following respiratory infection, with current attention focused on the clinical consequences of the Coronavirus pandemic. Epigenetic factors are increasingly recognized as important determinants of immune responses, and EZH2 is a prominent target due to the availability of highly specific and efficacious antagonists. However, very little is known about the role of EZH2 in the myeloid lineage. Here, we show EZH2 acts in macrophages to limit inflammatory responses to activation, and in neutrophils for chemotaxis. Selective genetic deletion in macrophages results in a remarkable gain in protection from infection with the prevalent lung pathogen, pneumococcus. In contrast, neutrophils lacking EZH2 showed impaired mobility in response to chemotactic signals, and resulted in increased susceptibility to pneumococcus. In summary, EZH2 shows complex, and divergent roles in different myeloid lineages, likely contributing to the earlier conflicting reports. Compounds targeting EZH2 are likely to impair mucosal immunity; however, they may prove useful for conditions driven by pulmonary neutrophil influx, such as adult respiratory distress syndrome.


Subject(s)
Enhancer of Zeste Homolog 2 Protein/immunology , Inflammation/immunology , Macrophages/immunology , Neutrophils/immunology , Animals , Cells, Cultured , Macrophages/cytology , Mice, Inbred C57BL , Neutrophils/cytology
7.
PLoS One ; 16(8): e0256784, 2021.
Article in English | MEDLINE | ID: covidwho-1378138

ABSTRACT

Viral sepsis has been proposed as an accurate term to describe all multisystemic dysregulations and clinical findings in severe and critically ill COVID-19 patients. The adoption of this term may help the implementation of more accurate strategies of early diagnosis, prognosis, and in-hospital treatment. We accurately quantified 110 metabolites using targeted metabolomics, and 13 cytokines/chemokines in plasma samples of 121 COVID-19 patients with different levels of severity, and 37 non-COVID-19 individuals. Analyses revealed an integrated host-dependent dysregulation of inflammatory cytokines, neutrophil activation chemokines, glycolysis, mitochondrial metabolism, amino acid metabolism, polyamine synthesis, and lipid metabolism typical of sepsis processes distinctive of a mild disease. Dysregulated metabolites and cytokines/chemokines showed differential correlation patterns in mild and critically ill patients, indicating a crosstalk between metabolism and hyperinflammation. Using multivariate analysis, powerful models for diagnosis and prognosis of COVID-19 induced sepsis were generated, as well as for mortality prediction among septic patients. A metabolite panel made of kynurenine/tryptophan ratio, IL-6, LysoPC a C18:2, and phenylalanine discriminated non-COVID-19 from sepsis patients with an area under the curve (AUC (95%CI)) of 0.991 (0.986-0.995), with sensitivity of 0.978 (0.963-0.992) and specificity of 0.920 (0.890-0.949). The panel that included C10:2, IL-6, NLR, and C5 discriminated mild patients from sepsis patients with an AUC (95%CI) of 0.965 (0.952-0.977), with sensitivity of 0.993(0.984-1.000) and specificity of 0.851 (0.815-0.887). The panel with citric acid, LysoPC a C28:1, neutrophil-lymphocyte ratio (NLR) and kynurenine/tryptophan ratio discriminated severe patients from sepsis patients with an AUC (95%CI) of 0.829 (0.800-0.858), with sensitivity of 0.738 (0.695-0.781) and specificity of 0.781 (0.735-0.827). Septic patients who survived were different from those that did not survive with a model consisting of hippuric acid, along with the presence of Type II diabetes, with an AUC (95%CI) of 0.831 (0.788-0.874), with sensitivity of 0.765 (0.697-0.832) and specificity of 0.817 (0.770-0.865).


Subject(s)
COVID-19/pathology , Metabolomics , Sepsis/diagnosis , Adult , Area Under Curve , COVID-19/complications , COVID-19/virology , Chemokines/blood , Cytokines/blood , Female , Humans , Kynurenine/blood , Lymphocytes/cytology , Male , Middle Aged , Neutrophils/cytology , ROC Curve , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Sepsis/etiology , Severity of Illness Index , Tryptophan/blood
8.
Diabetes Res Clin Pract ; 178: 108955, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1309207

ABSTRACT

AIMS: To create and compare survival models from admission laboratory indices in people hospitalized with coronavirus disease 2019 (COVID-19) with and without diabetes. METHODS: Retrospective observational study of patients with COVID-19 with or without diabetes admitted to Sheffield Teaching Hospitals from 29 February to 01 May 2020. Predictive variables for in-hospital mortality from COVID-19 were explored using Cox proportional hazard models. RESULTS: Out of 505 patients, 156 (30.8%) had diabetes mellitus (DM) of which 143 (91.7%) had type 2 diabetes. There were significantly higher in-hospital COVID-19 deaths in those with DM [DM COVID-19 deaths 54 (34.6%) vs. non-DM COVID-19 deaths 88 (25.2%): P < 0.05]. Activated partial thromboplastin time (APPT) > 24 s without anticoagulants (HR 6.38, 95% CI: 1.07-37.87: P = 0.04), APTT > 24 s with anticoagulants (HR 24.01, 95% CI: 3.63-159.01: P < 0.001), neutrophil-lymphocyte ratio > 8 (HR 6.18, 95% CI: 2.36-16.16: P < 0.001), and sodium > 136 mmol/L (HR 3.27, 95% CI: 1.12-9.56: P = 0.03) at admission, were only associated with in-hospital COVID-19 mortality for those with diabetes. CONCLUSIONS: At admission, elevated APTT with or without anticoagulants, neutrophil-lymphocyte ratio and serum sodium are unique factors that predict in-hospital COVID-19 mortality in patients with diabetes compared to those without. This novel finding may lead to research into haematological and biochemical mechanisms to understand why those with diabetes are more susceptible to poor outcomes when infected with Covid-19, and contribute to identification of those most at risk when admitted to hospital.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Hospital Mortality , Adolescent , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , COVID-19/diagnosis , COVID-19/mortality , Diabetes Mellitus, Type 2/complications , Female , Hospitalization , Hospitals, University , Humans , Lymphocytes/cytology , Male , Middle Aged , Neutrophils/cytology , Partial Thromboplastin Time , Retrospective Studies , Risk Factors , Sodium/blood , United Kingdom , Young Adult
9.
Cardiovasc Res ; 117(8): 1814-1822, 2021 07 07.
Article in English | MEDLINE | ID: covidwho-1301347

ABSTRACT

2020 has been an extraordinary year. The emergence of COVID-19 has driven urgent research in pulmonary and cardiovascular science and other fields. It has also shaped the way that we work with many experimental laboratories shutting down for several months, while bioinformatics approaches and other large data projects have gained prominence. Despite these setbacks, vascular biology research is stronger than ever. On behalf of the European Society of Cardiology Council for Basic Cardiovascular Science (ESC CBCS), here we review some of the vascular biology research highlights for 2020. This review is not exhaustive and there are many outstanding vascular biology publications that we were unable to cite due to page limits. Notwithstanding this, we have provided a snapshot of vascular biology research excellence in 2020 and identify topics that are in the ascendency and likely to gain prominence in coming years.


Subject(s)
COVID-19/diagnosis , Extracellular Traps/physiology , Neutrophils/cytology , Smartphone , Computational Biology , Humans , SARS-CoV-2/pathogenicity
10.
PLoS One ; 16(6): e0252599, 2021.
Article in English | MEDLINE | ID: covidwho-1285199

ABSTRACT

Inflammation has an important role in the progression of various viral pneumonia, including COVID-19. Circulating biomarkers that can evaluate inflammation and immune status are potentially useful in diagnosing and prognosis of COVID-19 patients. Even more so when they are a part of the routine evaluation, chest CT could have even higher diagnostic accuracy than RT-PCT alone in a suggestive clinical context. This study aims to evaluate the correlation between inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelets-to-lymphocytes ratio (PLR), and eosinophils with the severity of CT lesions in patients with COVID-19. The second objective was to seek a statically significant cut-off value for NLR and PLR that could suggest COVID-19. Correlation of both NLR and PLR with already established inflammatory markers such as CRP, ESR, and those specific for COVID-19 (ferritin, D-dimers, and eosinophils) were also evaluated. One hundred forty-nine patients with confirmed COVID-19 disease and 149 age-matched control were evaluated through blood tests, and COVID-19 patients had thorax CT performed. Both NLR and PLR correlated positive chest CT scan severity. Both NLR and PLR correlated positive chest CT scan severity. When NLR value is below 5.04, CT score is lower than 3 with a probability of 94%, while when NLR is higher than 5.04, the probability of severe CT changes is only 50%. For eosinophils, a value of 0.35% corresponds to chest CT severity of 2 (Se = 0.88, Sp = 0.43, AUC = 0.661, 95% CI (0.544; 0.779), p = 0.021. NLR and PLR had significantly higher values in COVID-19 patients. In our study a NLR = 2.90 and PLR = 186 have a good specificity (0.89, p = 0.001, respectively 0.92, p<0.001). Higher levels in NLR, PLR should prompt the clinician to prescribe a thorax CT as it could reveal important lesions that could influence the patient's future management.


Subject(s)
Blood Platelets/cytology , COVID-19/diagnostic imaging , COVID-19/immunology , Eosinophils/cytology , Neutrophils/cytology , Signal-To-Noise Ratio , Tomography, X-Ray Computed , Adult , COVID-19/pathology , Female , Humans , Lymphocyte Count , Male , Middle Aged
11.
Sci Rep ; 11(1): 13026, 2021 06 22.
Article in English | MEDLINE | ID: covidwho-1279902

ABSTRACT

The objective of the study was to develop and validate a prediction model that identifies COVID-19 patients at risk of requiring oxygen support based on five parameters: C-reactive protein (CRP), hypertension, age, and neutrophil and lymphocyte counts (CHANeL). This retrospective cohort study included 221 consecutive COVID-19 patients and the patients were randomly assigned randomly to a training set and a test set in a ratio of 1:1. Logistic regression, logistic LASSO regression, Random Forest, Support Vector Machine, and XGBoost analyses were performed based on age, hypertension status, serial CRP, and neutrophil and lymphocyte counts during the first 3 days of hospitalization. The ability of the model to predict oxygen requirement during hospitalization was tested. During hospitalization, 45 (41.8%) patients in the training set (n = 110) and 41 (36.9%) in the test set (n = 111) required supplementary oxygen support. The logistic LASSO regression model exhibited the highest AUC for the test set, with a sensitivity of 0.927 and a specificity of 0.814. An online risk calculator for oxygen requirement using CHANeL predictors was developed. "CHANeL" prediction models based on serial CRP, neutrophil, and lymphocyte counts during the first 3 days of hospitalization, along with age and hypertension status, provide a reliable estimate of the risk of supplement oxygen requirement among patients hospitalized with COVID-19.


Subject(s)
C-Reactive Protein/analysis , COVID-19/pathology , Hypertension/complications , Lymphocytes/cytology , Neutrophils/cytology , Oxygen Inhalation Therapy , Age Factors , Aged , Area Under Curve , Biomarkers/analysis , Biomarkers/metabolism , COVID-19/complications , COVID-19/virology , Female , Humans , Logistic Models , Lymphocytes/metabolism , Male , Middle Aged , Neutrophils/metabolism , ROC Curve , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index , Support Vector Machine
12.
Am J Clin Pathol ; 156(2): 185-197, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1276141

ABSTRACT

OBJECTIVES: We compared complete blood count (CBC) with differential and markers of inflammation and coagulation in patients with and without coronavirus disease 2019 (COVID-19) presenting to emergency departments in Seattle, WA. METHODS: We reviewed laboratory values for 1 week following each COVID-19 test for adult patients who received a standard severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) test before April 13, 2020. Results were compared by COVID-19 status and clinical course. RESULTS: In total 1,027 patients met inclusion criteria. Patients with COVID-19 (n = 155) had lower leukocytes (P < .0001), lymphocytes (P < .0001), platelets (P < .0001), and higher hemoglobin (P = .0140) than those without, but absolute differences were small. Serum albumin was lower in patients with COVID-19 (P < .0001) and serum albumin, neutrophil to lymphocyte ratio (NLR), and red cell distribution width (RDW) were each associated with disease severity. NLR did not differ between patients with COVID-19 and those without (P = .8012). CONCLUSIONS: Patients with COVID-19 had modestly lower leukocyte, lymphocyte, and platelet counts and higher hemoglobin values than patients without COVID-19. The NLR, serum albumin, and RDW varied with disease severity, regardless of COVID-19 status.


Subject(s)
Blood Cell Count , Blood Coagulation , COVID-19/blood , Inflammation/blood , Lymphocytes/cytology , Adult , Biomarkers/blood , Blood Cell Count/methods , COVID-19/diagnosis , Emergency Service, Hospital , Humans , Leukocyte Count/methods , Lymphocyte Count/methods , Male , Middle Aged , Neutrophils/cytology , Platelet Count/methods , SARS-CoV-2/pathogenicity
13.
Eur Rev Med Pharmacol Sci ; 25(10): 3868-3878, 2021 05.
Article in English | MEDLINE | ID: covidwho-1264763

ABSTRACT

OBJECTIVE: This study aimed to compare the mortality rate between advanced-stage non-small cell lung cancer patients (NSCLC) with and without COVID-19. This study also explores the possible laboratory characteristics used for prognostication in patients with NSCLC and COVID-19. Additionally, this study evaluated potential differences in laboratory values between the case and control groups. PATIENTS AND METHODS: This is a single-center retrospective cohort study conducted in Dharmais National Cancer Hospital, Indonesia, enrolling patients with NSCLC undergoing chemotherapy or targeted therapy between May 2020 and January 2021. All patients with NSCLC and COVID-19 in these periods were enrolled into the case group. The control group was age-matched NSCLC patients without COVID-19 that was derived from the NSCLC cohort through randomization. RESULTS: There were 342 patients with NSCLC between May 2020 and January 2021. Twenty-seven (7.9%) of the patients were infected by COVID-19. To facilitate comparison, thirty-five age-matched controls with NSCLC were selected from the cohort. The mortality rate in patients with COVID-19 was 46.2%. Eleven patients (40.7%) had severe COVID-19, of which none survived. NLR >8.35 has a sensitivity of 83.3%, specificity of 92.9%, LR+ of 12, and LR- of 0.18. The AUC was 0.946 (95% CI 0.867-1.000), p<0.001. PLR >29.14 has a sensitivity of 75.0%, specificity of 71.4%, LR+ 2.62, LR- 0.35, and AUC 0.851 (95% CI 0.706-0.996), p=0.002. Both NLR and PLR were associated with shorter time-to-mortality in the unadjusted and adjusted model CONCLUSIONS: NLR and PLR are independent predictors of mortality in COVID-19 patients with NSCLC.


Subject(s)
Blood Platelets/cytology , COVID-19/diagnosis , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/mortality , Lymphocytes/cytology , Neutrophils/cytology , Aged , Area Under Curve , COVID-19/complications , COVID-19/virology , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Indonesia , Lung Neoplasms/complications , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , ROC Curve , Retrospective Studies , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Survival Rate
14.
Virol J ; 18(1): 115, 2021 06 04.
Article in English | MEDLINE | ID: covidwho-1259204

ABSTRACT

BACKGROUND: It is important to recognize the coronavirus disease 2019 (COVID-19) patients in severe conditions from moderate ones, thus more effective predictors should be developed. METHODS: Clinical indicators of COVID-19 patients from two independent cohorts (Training data: Hefei Cohort, 82 patients; Validation data: Nanchang Cohort, 169 patients) were retrospected. Sparse principal component analysis (SPCA) using Hefei Cohort was performed and prediction models were deduced. Prediction results were evaluated by receiver operator characteristic curve and decision curve analysis (DCA) in above two cohorts. RESULTS: SPCA using Hefei Cohort revealed that the first 13 principal components (PCs) account for 80.8% of the total variance of original data. The PC1 and PC12 were significantly associated with disease severity with odds ratio of 4.049 and 3.318, respectively. They were used to construct prediction model, named Model-A. In disease severity prediction, Model-A gave the best prediction efficiency with area under curve (AUC) of 0.867 and 0.835 in Hefei and Nanchang Cohort, respectively. Model-A's simplified version, named as LMN index, gave comparable prediction efficiency as classical clinical markers with AUC of 0.837 and 0.800 in training and validation cohort, respectively. According to DCA, Model-A gave slightly better performance than others and LMN index showed similar performance as albumin or neutrophil-to-lymphocyte ratio. CONCLUSIONS: Prediction models produced by SPCA showed robust disease severity prediction efficiency for COVID-19 patients and have the potential for clinical application.


Subject(s)
COVID-19/diagnosis , COVID-19/pathology , Principal Component Analysis/methods , Severity of Illness Index , Adult , Aged , Biomarkers/analysis , Female , Humans , Leukocyte Count , Lymphocyte Count , Lymphocytes/cytology , Male , Middle Aged , Models, Biological , Monocytes/cytology , Neutrophils/cytology , Retrospective Studies , SARS-CoV-2
15.
PLoS One ; 16(5): e0251426, 2021.
Article in English | MEDLINE | ID: covidwho-1243844

ABSTRACT

Two SARS-CoV-2 variants of concern showing increased transmissibility relative to the Wuhan virus have recently been identified. Although neither variant appears to cause more severe illness nor increased risk of death, the faster spread of the virus is a major threat. Using computational tools, we found that the new SARS-CoV-2 variants may acquire an increased transmissibility by increasing the propensity of its spike protein to expose the receptor binding domain via proteolysis, perhaps by neutrophil elastase and/or via reduced intramolecular interactions that contribute to the stability of the closed conformation of spike protein. This information leads to the identification of potential treatments to avert the imminent threat of these more transmittable SARS-CoV-2 variants.


Subject(s)
Pancreatic Elastase/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Amino Acid Sequence , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Neutralizing/immunology , COVID-19/pathology , COVID-19/virology , Humans , Molecular Dynamics Simulation , Mutation , Neutrophils/cytology , Neutrophils/metabolism , Protein Binding , Protein Stability , Protein Structure, Tertiary , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Sequence Alignment , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
16.
PLoS One ; 16(5): e0249964, 2021.
Article in English | MEDLINE | ID: covidwho-1232459

ABSTRACT

Coronavirus disease 2019 (COVID-19) is highly contagious and has affected the whole world. We seek to investigate the clinical and laboratory characteristics of COVID-19 patients in the high altitude areas of Sichuan, China. In this retrospective cohort study, a total of 67 patients with laboratory-confirmed SARS-CoV-2 infections in Sichuan's Ngawa Tibetan and Qiang Autonomous Prefecture were included from February 1, 2020, to March 2, 2020. Their clinical characteristics, as well as radiological and laboratory features, were extracted. Four (6.0%) patients were categorized as severe cases; 39 (58.2%) were non-severe cases, and 24 (35.8%) were asymptomatic cases. A total of 46 (68.7%) patients were associated with cluster infection events in this study. The most common symptoms were cough, sputum production, dyspnea, fatigue or myalgia, and headache. Seven (10.4%) patients showed leucopenia, and 20 (29.9%) patients showed lymphopenia. Lymphocyte counts and neutrophil-to-lymphocyte ratios (NPR) were different between the three groups. In total, 14 (20.9%) patients had thrombocytopenia, and prothrombin times (PT) and fibrinogen levels differed between groups. We also found significant differences in sodium, chloride and calcium levels between the three groups. Antiviral therapy did not lead to obvious adverse events or shortened durations from initial positive to subsequent negative nuclei acid tests. Advanced age, hypertension, high neutrophil count, the neutrophil-to-lymphocyte ratio, fibrinogen and lactate dehydrogenase levels were identified as independent risk factors for symptomatic cases of COVID-19. In conclusion, the symptoms of patients in high altitude areas were mild, and about one third were asymptomatic. We also identified several independent risk factors for symptomatic cases of COVID-19.


Subject(s)
COVID-19/pathology , Adolescent , Adult , Aged , Altitude , COVID-19/complications , COVID-19/epidemiology , COVID-19/virology , China/epidemiology , Cough/etiology , Female , Fibrinogen/analysis , Humans , L-Lactate Dehydrogenase/metabolism , Lymphocytes/cytology , Male , Middle Aged , Neutrophils/cytology , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Young Adult
17.
Eur J Med Res ; 26(1): 45, 2021 May 14.
Article in English | MEDLINE | ID: covidwho-1229005

ABSTRACT

BACKGROUND: Hematological comparison of coronavirus disease (COVID-19) and other viral pneumonias can provide insights into COVID-19 treatment. METHODS: In this retrospective case-control single-center study, we compared the data of 126 patients with viral pneumonia during different outbreaks [severe acute respiratory syndrome (SARS) in 2003, influenza A (H1N1) in 2009, human adenovirus type 7 in 2018, and COVID-19 in 2020]. RESULTS: One of the COVID-19 characteristics was a continuous decline in the hemoglobin level. The neutrophil count was related to the aggravation of COVID-19 and SARS. Thrombocytopenia occurred in patients with SARS and severe COVID-19 even at the recovery stage. Lymphocytes were related to the entire course of adenovirus infection, recovery of COVID-19, and disease development of SARS. CONCLUSIONS: Dynamic changes in hematological counts could provide a reference for the pathogenesis and prognosis of pneumonia caused by respiratory viruses in clinics.


Subject(s)
Adenovirus Infections, Human/blood , COVID-19/blood , Influenza, Human/blood , Pneumonia, Viral/blood , Severe Acute Respiratory Syndrome/blood , Adenovirus Infections, Human/pathology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/pathology , Case-Control Studies , Female , Hemoglobins/analysis , Humans , Influenza, Human/pathology , Lymphocyte Count , Male , Middle Aged , Neutrophils/cytology , Pneumonia, Viral/pathology , Retrospective Studies , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/pathology , Thrombocytopenia/pathology , Young Adult
18.
Biomolecules ; 11(5)2021 05 06.
Article in English | MEDLINE | ID: covidwho-1223942

ABSTRACT

SARS-CoV-2 is a member of the family of coronaviruses associated with severe outbreaks of respiratory diseases in recent decades and is the causative agent of the COVID-19 pandemic. The recognition by and activation of the innate immune response recruits neutrophils, which, through their different mechanisms of action, form extracellular neutrophil traps, playing a role in infection control and trapping viral, bacterial, and fungal etiological agents. However, in patients with COVID-19, activation at the vascular level, combined with other cells and inflammatory mediators, leads to thrombotic events and disseminated intravascular coagulation, thus leading to a series of clinical manifestations in cerebrovascular, cardiac, pulmonary, and kidney disease while promoting severe disease and mortality. Previous studies of hospitalized patients with COVID-19 have shown that elevated levels of markers specific for NETs, such as free DNA, MPO, and H3Cit, are strongly associated with the total neutrophil count; with acute phase reactants that include CRP, D-dimer, lactate dehydrogenase, and interleukin secretion; and with an increased risk of severe COVID-19. This study analyzed the interactions between NETs and the activation pathways involved in immunothrombotic processes in patients with COVID-19.


Subject(s)
COVID-19/pathology , Extracellular Traps/metabolism , Thrombosis/immunology , Thrombosis/pathology , Biomarkers/metabolism , COVID-19/immunology , COVID-19/virology , Complement System Proteins/metabolism , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/pathology , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/pathology , Humans , Neutrophils/cytology , Neutrophils/immunology , Neutrophils/metabolism , SARS-CoV-2/isolation & purification , Thrombosis/metabolism
19.
EMBO Mol Med ; 13(6): e14045, 2021 06 07.
Article in English | MEDLINE | ID: covidwho-1219070

ABSTRACT

The immune responses and mechanisms limiting symptom progression in asymptomatic cases of SARS-CoV-2 infection remain unclear. We comprehensively characterized transcriptomic profiles, cytokine responses, neutralization capacity of antibodies, and cellular immune phenotypes of asymptomatic patients with acute SARS-CoV-2 infection to identify potential protective mechanisms. Compared to symptomatic patients, asymptomatic patients had higher counts of mature neutrophils and lower proportion of CD169+ expressing monocytes in the peripheral blood. Systemic levels of pro-inflammatory cytokines were also lower in asymptomatic patients, accompanied by milder pro-inflammatory gene signatures. Mechanistically, a more robust systemic Th2 cell signature with a higher level of virus-specific Th17 cells and a weaker yet sufficient neutralizing antibody profile against SARS-CoV-2 was observed in asymptomatic patients. In addition, asymptomatic COVID-19 patients had higher systemic levels of growth factors that are associated with cellular repair. Together, the data suggest that asymptomatic patients mount less pro-inflammatory and more protective immune responses against SARS-CoV-2 indicative of disease tolerance. Insights from this study highlight key immune pathways that could serve as therapeutic targets to prevent disease progression in COVID-19.


Subject(s)
COVID-19/pathology , Carrier State/immunology , Biomarkers/metabolism , Brain-Derived Neurotrophic Factor/metabolism , COVID-19/immunology , COVID-19/virology , Carrier State/pathology , Carrier State/virology , Cytokines/metabolism , Humans , Monocytes/cytology , Monocytes/immunology , Monocytes/metabolism , Neutrophils/cytology , Neutrophils/immunology , Neutrophils/metabolism , SARS-CoV-2/isolation & purification , Th17 Cells/cytology , Th17 Cells/immunology , Th17 Cells/metabolism , Transcriptome , Up-Regulation , Vascular Endothelial Growth Factor D/metabolism
20.
J Med Virol ; 93(2): 1029-1037, 2021 02.
Article in English | MEDLINE | ID: covidwho-1196434

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 infection. This study aims to examine the changes in peripheral blood parameters during the early stages of COVID-19 and influenza. We analyzed the peripheral blood parameters of 169 COVID-19 patients and 131 influenza patients during the early-onset stage. Results from the patients with COVID-19 were compared with those from healthy controls and influenza patients. In addition, results from patients with common and severe COVID-19 were further compared. There were significant differences between COVID-19 and influenza patients in terms of age, white blood cell count, platelet count, percentage of neutrophils, percentage of lymphocytes, percentage of monocytes, percentage of eosinophils, percentage of basophils, neutrophil, count and monocyte count. Two parameters (monocyte count and percentage of basophils) were combined to clarify the diagnostic efficacy of COVID-19 and influenza and the area under the curve was found to be 0.772. Comparison of peripheral blood parameters from common COVID-19, severe COVID-19, and influenza patients revealed many differences during the early disease stages. The diagnostic formula developed by this study will be of benefit for physicians in the differentiation of COVID-19 and influenza.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Influenza, Human/blood , Influenza, Human/diagnosis , Adolescent , Adult , Aged , China , Diagnosis, Differential , Female , Humans , Leukocyte Count , Lymphocytes/cytology , Male , Middle Aged , Monocytes/cytology , Neutrophils/cytology , Platelet Count , Young Adult
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