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BACKGROUND: Extracellular vesicles (EVs) play a key role in cell communication and the pathogenesis of some diseases. EVs may accelerate cell death during the course of mycobacterial infection and are also considered as a new vaccine design, drug delivery, and biomarker candidates. The current study evaluates the effects of EVs from serum samples of mycobacteria-infected patients on THP-1 monocytes and PBMC cells. METHOD: EVs were purified from the serum, then cultured separately with THP-1 monocytes and PBMCs. The cell death was determined through annexin V-FITC and PI staining. GW4869, an EVs inhibitor, was used to determine if EVs released from serum could increase THP-1 monocytes cell death. RESULTS: The cell death was significantly increased in the presence of 10 µg/ml and 5 µg/ml concentrations of the purified EVs (p < 0.05). Minimal cell death was determined in 2.5 µg/ml and 1.2 µg/ml (p < 0.05). Up to 85% of the cells were viable in the presence of the GW4869 inhibitor (p < 0.05). CONCLUSION: Direct infection of the cells with EVs released from mycobacteria-infected patients samples, the multiplicity of infection with the EVs, and virulent or avirulent mycobacteria may change the status of the cell death. The isolated EVs from serum samples of patients with mycobacterial infection accelerated cell death, which means that they might not be considered as an optimal tool for developing drug delivery and vaccine against tuberculosis.
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Morte Celular , Vesículas Extracelulares/metabolismo , Infecções por Mycobacterium/imunologia , Mycobacterium/fisiologia , Adulto , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Mycobacterium/imunologia , Infecções por Mycobacterium/metabolismo , Infecções por Mycobacterium/microbiologia , Células THP-1 , VirulênciaRESUMO
The coronavirus disease COVID-19 was first described in December 2019. The peripheral blood of COVID-19 patients have increased numbers of neutrophils which are important in controlling the bacterial infections observed in COVID-19. We sought to evaluate the cytotoxic capacity of neutrophils in COVID-19 patients. 34 confirmed COVID-19 patients (29 severe, five mild disease), and nine healthy controls were recruited from the Masih Daneshvari Hospital (Tehran, Iran) from March to May 2020. Polymorphonuclear (PMN) cells were isolated from whole blood and incubated with green fluorescent protein (GFP)-labelled methicillin-resistant Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). Bacterial growth was determined by measuring the florescence of co-cultures of bacteria and neutrophils and reported as the lag time before exponential growth. The number of viable bacteria was determined after 70 hours as colony-forming units (CFU). The immunophenotype of tested cells was evaluated by flow cytometry. Isolated neutrophils have higher surface expression of CD16 and CD62L with negative markers for PMN-MDSC. Bacterial growth in the presence of SA (22 ± 0.9 versus 9.2 ± 0.5 h, P < .01) and PA (12.4 ± 0.6 versus 4.5 ± 0.22, P < .01) was significantly reduced in COVID-19 patients. After 70 h incubation of PMN with bacteria (SA and PA), CFUs were significant increased in COVID-19 patients SA (2.6 ± 0.09 × 108 CFU/mL-severe patients and 1.4 ± 0.06 × 108 CFU/mL-mild patients, P < .001) and PA (2.2 ± 0.09 × 109 CFU/mL-severe patients and 1.6 ± 0.03 × 109 CFU/mL-mild patients, P < .001). Gentamycin proliferation assays confirmed the presence of intracellular bacteria. Reduced bacterial killing by neutrophils from COVID-19 patients may be responsible for the high bacterial yield seen in these patients.
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COVID-19 , Staphylococcus aureus Resistente à Meticilina , Humanos , Irã (Geográfico) , Neutrófilos/microbiologia , Pseudomonas aeruginosa , Staphylococcus aureusRESUMO
Dendritic cells (DCs) orchestrate innate inflammatory responses and adaptive immunity through T-cell activation via direct cell-cell interactions and/or cytokine production. Tolerogenic DCs (tolDCs) help maintain immunological tolerance through the induction of T-cell unresponsiveness or apoptosis, and generation of regulatory T cells. Mesenchymal stromal cells (MSCs) are adult multipotent cells located within the stroma of bone marrow (BM), but they can be isolated from virtually all organs. Extracellular vesicles and exosomes are released from inflammatory cells and act as messengers enabling communication between cells. To investigate the effects of MSC-derived exosomes on the induction of mouse tolDCs, murine adipose-derived MSCs were isolated from C57BL/6 mice and exosomes isolated by ExoQuick-TC kits. BM-derived DCs (BMDCs) were prepared and cocultured with MSCs-derived exosomes (100 µg/ml) for 72 hr. Mature BMDCs were derived by adding lipopolysaccharide (LPS; 0.1µg/ml) at Day 8 for 24 hr. The study groups were divided into (a) immature DC (iDC, Ctrl), (b) iDC + exosome (Exo), (c) iDC + LPS (LPS), and (d) iDC + exosome + LPS (EXO + LPS). Expression of CD11c, CD83, CD86, CD40, and MHCII on DCs was analyzed at Day 9. DC proliferation was assessed by coculture with carboxyfluorescein succinimidyl ester-labeled BALB/C-derived splenocytes p. Interleukin-6 (IL-6), IL-10, and transforming growth factor-ß (TGF-ß) release were measured by enzyme-linked immunosorbent assay. MSC-derived exosomes decrease DC surface marker expression in cells treated with LPS, compared with control cells ( ≤ .05). MSC-derived exosomes decrease IL-6 release but augment IL-10 and TGF-ß release (p ≤ .05). Lymphocyte proliferation was decreased (p ≤ .05) in the presence of DCs treated with MSC-derived exosomes. CMSC-derived exosomes suppress the maturation of BMDCs, suggesting that they may be important modulators of DC-induced immune responses.
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Células Dendríticas/imunologia , Exossomos/imunologia , Tolerância Imunológica/imunologia , Células-Tronco Mesenquimais/imunologia , Animais , Biomarcadores/metabolismo , Comunicação Celular/imunologia , Proliferação de Células/fisiologia , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Células Dendríticas/metabolismo , Exossomos/metabolismo , Feminino , Imunidade/imunologia , Inflamação/imunologia , Inflamação/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BLRESUMO
An amendment to this paper has been published and can be accessed via the original article.
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In the last decade, autosomal recessive interleukin-12 receptor ß1 (IL-12Rß1) deficiency, the most common cause of Mendelian susceptibility to mycobacterial disease (MSMD), has been diagnosed in a few children and adults with severe tuberculosis in Iran. Here, we report three cases referred to the Immunology, Asthma and Allergy ward at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD) at Masih Daneshvari Hospital from 2012 to 2017 with Mycobacterium tuberculosis and non-tuberculous mycobacteria infections due to defects in IL-12Rß1 but with different clinical manifestations. All three were homozygous for either an IL-12Rß1 missense or nonsense mutation that caused the IL-12Rß1 protein not to be expressed on the cell membrane and completely abolished the cellular response to recombinant IL-12. Our findings suggest that the presence of IL-12Rß1 deficiency should be determined in children with mycobacterial infections at least in countries with a high prevalence of parental consanguinity and in areas endemic for TB like Iran.
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Mutação , Infecções por Mycobacterium/genética , Receptores de Interleucina-12/genética , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Humanos , Irã (Geográfico) , Masculino , Mycobacterium/isolamento & purificação , Infecções por Mycobacterium/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Linhagem , Receptores de Interleucina-12/imunologia , Tuberculose/genética , Tuberculose/microbiologiaRESUMO
Ataxia-telangiectasia (A-T), a rare inherited disorder, usually affects the nervous and immune systems, and occasionally other organs. A-T is associated mainly with mutations in the ataxia telangiectasia mutated (ATM) gene, which encodes a protein kinase that has a major role in the cellular response to DNA damage. We report here a novel ATM mutation (c.3244_3245insG; p.His1082fs) in an 11-year old female. This subject presented with typical features, with the addition of chest manifestations including mediastinal lymphadenopathy and diffuse bilateral micronodular infiltration of the lungs, along with a high EBV titer. The subject died as a result of rapid B-cell lymphoma progression before chemotherapy could be initiated. This case highlights the need for the rapid diagnosis of A-T mutations and the detection of associated life-threatening outcomes such as cancers.
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Proteínas Mutadas de Ataxia Telangiectasia/genética , Ataxia Telangiectasia/genética , Mutação , Ataxia Telangiectasia/patologia , Criança , Feminino , Humanos , Mutação/genética , PrognósticoRESUMO
BACKGROUND: Tuberculosis (TB) is a major global health problem, and there is an association between tobacco smoke and TB. Water pipe smoking has become an increasing problem not only in Middle Eastern countries but also globally because users consider it as safer than cigarettes. The presence of high levels of toxic substances in water-pipe smoke may be a predisposing factor that enhances the incidence of pulmonary disorders. For example, uncontrolled macropinocytosis in alveolar epithelial cells following exposure to water-pipe smoke may predispose subjects to pulmonary infection. Here, we studied the effects of water-pipe condense (WPC) on the internalization of Mycobacterium Bovis BCG by macropinocytosis in the alveolar epithelial cell line A549. METHODS: A549 cells were exposed to WPC (4 mg/ml) for 24, 48, 72 and 96 h. Cell viability was studied using the methyl thiazolyldipenyl-tetrazolium bromide (MTT) reduction assay and proliferation by bromodeoxyUridine (BrdU) incorporation. Cells were exposed to FITC-Dextran (1 mg/ml) (as a control) and FITC-BCG (MOI = 10) for 20 min at 37 °C before cells were collected and the uptake of BCG-FITC determined by flow cytometry. Similar experiments were performed at 4 °C as a control. The Rho-associated protein kinase (ROCK) inhibitor Y-27632 (1 µM) was used to assess the mechanism by which WPC enhanced BCG uptake. RESULTS: WPC (4 mg/ml) increased the uptake of BCG-FITC after 72 (1.3 ± 0.1 fold, p < 0.05) and 96 (1.4 ± 0.05 fold, p < 0.05) hours. No effect on BCG-FITC uptake was observed at 24 or 48 h. WPC also significantly increased the uptake of FITC-Dextran (2.9 ± 0.3 fold, p < 0.05) after 24 h. WPC significantly decreased cell viability after 24 (84 ± 2%, p < 0.05), 48 (78±, 3%, p < 0.05), 72 (64 ± 2%, p < 0.05) and 96 h (45 ± 2%, p < 0.05). Y-27632 completely attenuated the increased uptake of BCG by WPC. Cell proliferation showed a decreasing trend in a time-dependent manner with WPC exposure. CONCLUSION: WPC exposure increased epithelial cell endocytosis activity and death as well as enhancing their capacity for macropinocytosis. Our in vitro data indicates possible harmful effects of WPC on the ability of lung epithelial cells to phagocytose mycobacterium.
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Células Epiteliais Alveolares/efeitos dos fármacos , Mycobacterium bovis , Fagocitose , Fumaça/efeitos adversos , Células A549 , Células Epiteliais Alveolares/microbiologia , Amidas/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citometria de Fluxo , Humanos , Piridinas/administração & dosagem , Nicotiana/químicaRESUMO
INTRODUCTION: In severe COVID-19 patients, acute respiratory distress syndrome (ARDS)-induced lung injury regularly causes a pulmonary fibrotic phase. There is no approved therapy for the COVID-19-induced pulmonary fibrosis. However, administration of an anti-fibrotic agent, in the early acute phase of the severe COVID-19 with ARDS, may improve the infection outcomes. AREAS COVERED: In this review, the main characteristics of nintedanib and its usefulness to treat COVID-19-induced fibrosis were studied. In July 2022, a literature search was performed from PubMed, Google Scholar, and the WHO databases for studies focusing on the properties, function, efficacy, and safety of nintedanib against different lung injuries. EXPERT OPINION: Nintedanib interferes with lung fibrosis and tumor angiogenesis by targeting multiple receptor tyrosine kinases (RTKs). Loss of RTKs activity leads to blocking downstream signaling cascades and inhibiting the proliferation and migration of lung fibroblasts. Targeting RTKs may be useful in the treatment of COVID-19 lung fibrosis. Nintedanib may be a superior agent compared to pirfenidone for the treatment of COVID-19 ARDS-related pulmonary fibrosis. Investigation of the efficacy and safety of nintedanib in the early stages of COVID-19-induced ARDS is critical since it may decrease the oxygen dependency and degree of lung fibrosis after the hospital discharge.
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COVID-19 , Fibrose Pulmonar Idiopática , Lesão Pulmonar , Síndrome do Desconforto Respiratório , Humanos , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Fibrose Pulmonar Idiopática/patologia , COVID-19/complicações , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/etiologiaRESUMO
Background and Aim: The efficacy of Sequential Organ Failure Assessment (SOFA) score as predictor of clinical outcomes among ICU-admitted COVID-19 patients is still controversial. We aimed to assess whether SOFA-score in different time intervals could predict 28-day mortality compared with other well-acknowledged risk factors of COVID-19 mortality. Methods: This observational prospective cohort was conducted on 1057 patients from March 2020 to March 2022 at Masih Daneshvari Hospital, Iran. The univariate and multivariate Cox proportional analysis were performed to assess the hazards of SOFA-score models. Receiver operating characteristic (ROC) curves were designed to estimate the predictive values. Results: Mean SOFA-score during first 96 h (HR: 3.82 [CI: 2.75-5.31]), highest SOFA-score (HR: 2.70 [CI: 1.93-3.78]), and initial SOFA-score (HR: 1.65 [CI: 1.30-2.11]) had strongest association with 28-day mortality (p < .0001). In contrast, SOFA scores at 48 and 96 h as well as Δ-SOFA: 48-0 h and Δ-SOFA: 96-0 h did not show significant correlations. Among them, merely mean SOFA-score (HR: 2.28 [CI: 2.21-3.51]; p < .001) remained as independent prognosticator on multivariate regression analysis; though having less odds of predicting value compared with age (HR: 3.81 [CI: 1.98-5.21]), hypertension (HR: 3.11 [CI: 1.26-3.81]), coronary artery disease [CAD] (HR: 2.82 [CI: 1.51-4.8]), and diabetes mellitus (HR: 2.45 [CI: 1.36-2.99]). The area under ROC (AUROC) for mean SOFA-score (0.77) and highest SOFA-score (0.71) were larger than other SOFA intervals. Calculating the first 96 h of SOFA trends, it was obtained that fatality rate was <12.3% if the score dropped, between 28.8% and 46.29% if the score remained unchanged, and >50.45% if the score increased. Conclusion: To predict the 28-day mortality among ICU-admitted COVID-19 patients, mean SOFA upon first 96 h of ICU stay is reliable; while having inadequate accuracy comparing with well-acknowledged COVID-19 mortality predictors (age, diabetes mellitus, hypertension, CAD). Notably, increased SOFA levels in the course of first 96 h of ICU-admission, prognosticate at least 50% fatality regardless of initial SOFA score.
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Background: Coronavirus disease 2019 (COVID-19) is a newly emerged disease with many unknown facets, so both the treatment and the cause of spreading this disease have remained mysterious so far. Materials and Methods: Based on the information of 4372 patients with COVID-19 referring to Dr. Masih Daneshvari Hospital in Tehran, the time-dependent changes in COVID-19 severity were investigated in this study using correlation analysis. Results: According to the results of this study, on average 154.80 patients were infected with mild to moderate COVID-19, and 39.06 were infected with severe COVID-19. The results of this study also indicated a descending trend in the number of patients with mild to moderate COVID-19 (r=-0.40, P-value=0.004) and an ascending trend in the number of patients with severe COVID-19 (r=0.43, P-value=0.003) overtime on a daily basis so that almost two patients were removed from those with mild to moderate COVID-19 and one was added to the patients with severe COVID-19 on average per day. Conclusion: Based on the current study results, it is concluded that COVID-19 severity will not be constant over time, and there is a probability of COVID-19 becoming more aggressive. Therefore, by the lack of timely control of the disease over time, we will witness an increased number of patients with severe COVID-19 and an increased number of hospitalizations in the intensive care unit (ICU) ward.
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Background: The disease process involves the occurrences happening during the disease and treatment course for the patient. Investigating this process is a significant and necessary issue for all diseases, including coronavirus disease 2019 (COVID-19). Materials and Methods: Using the information of 4372 patients with COVID-19 referring to Dr. Masih Daneshvari Hospital in Tehran during the COVID-19 epidemic, being hospitalized, cared for, and home quarantined due to having mild symptoms, the COVID-19 process and its related occurrences were investigated during the treatment course. Results: In the COVID-19 course, considering the disease severity, the likelihood of hospitalization in the general ward or the intensive care unit (ICU) ward, the likelihood of isolation or home quarantine, and the likelihood of occurrences such as recovery or death at the end of the disease course were taken into consideration. Based on the results of this study, the likelihood of hospitalization in the general ward, the ICU ward, and isolation or home quarantine was determined to be approximately 49.54%, 14.73%, and 35.73%, respectively. Also, for patients hospitalized in the general ward, the ICU ward, and isolated or home quarantined, the likelihood of recovery was estimated at approximately 64.79%, 10.82%, and 96.31%, respectively, and the likelihood of death was also estimated at about 35.21%, 89.18%, and 3.69% respectively. Conclusion: Investigating the COVID-19 process and estimating the likelihood of incidence of its related occurrences during the treatment course both create an accurate prognosis and provide the possibility of achieving an efficient treatment for these patients.
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Background: The world is currently struggling with the COVID-19pandemic. Measures to control the COVID-19 pandemic have affected other health problems and diseases, including tuberculosis (TB) and its control. The present narrative review aimed at reviewing published literature on the impact of the COVID-19 pandemic on TB control. Materials and Methods: English language databases, including PubMed, ISI, Scopus, and Google Scholar, were searched using the keywords "Tuberculosis, COVID-19, and Coronavirus" to find relevant articles. Results: Problems and limitations in financial and human resources, as well as medical and laboratory services caused by the COVID-19 pandemic, contribute to the reduction in the number of newly diagnosed patients with TB. More effort in identifying patients with TB is of great importance, and if the global number of newly diagnosed patients with TB decreases by 25% for three consecutive months due to the COVID-19 pandemic, the TB mortality rate will increase by 13%. An increase in the TB mortality rate means the failure of TB control programs to reach the targets of the Global End TB Strategy. Conclusion: According to the latest statistics released by the Ministry of Health, the incidence of TB in Iran has not yet reached fewer than 100 cases per million population. On the other hand, being a neighbor with countries with a high risk of TB is a serious threat to Iran. Therefore, further effort to control TB during the COVID-19 pandemic is particularly important.
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Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in white Caucasians. It affects many organs including the lung, pancreas, and liver. Whilst CF is a monogenic disease, several studies revealed a complex relationship between genotype and clinical phenotype of diseases. We examined the expression of human leukocyte antigen (HLA) class II alleles among Iranian CF patients with disease-related microbial infection. This study was conducted on 50 hospitalized CF patients (27 males, 23 females aged 15.5±6.5 years), and 50 healthy age- and gender-matched control subjects. 5ml whole blood was harvested and after isolation of genomic DNA, HLA-DRB1 subtypes were determined by single specific primer polymerase chain reaction methods. HLA-DRB1*10 was less frequent and HLA-DRB1*04 and HLA-DRB1*11 was the most frequent allele in CF patients, but none reached significance. HLA-DRB1*04 allele was frequently seen among16 CF patients with high serum IgE levels (430.25±219.7 IU/mL) and 27 CF patients that were positive for Pseudomonas aeruginosa colonization. A total of 31 CF patients had candida Albicans colonization in whom HLA-DRB1*11 was mostly seen. A total of 3 CF patients had allergic bronchopulmonary aspergillosis and two were diabetic. The DR4 and DR11 serotypes that recognize the HLA-DRB1*04 and HLA-DRB1*11 gene products respectively are not significantly enriched in the Iranian CF population. Further research should be conducted on DR4 and DR11 in CF patients to understand their possible role in infection and IgE expression.
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Fibrose Cística , Alelos , Fibrose Cística/genética , Feminino , Cadeias HLA-DRB1/genética , Humanos , Imunoglobulina E , Irã (Geográfico) , MasculinoRESUMO
The pathogenesis of coronavirus disease 2019 (COVID-19) is not fully elucidated. COVID-19 is due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes severe illness and death in some people by causing immune dysregulation and blood T cell depletion. Increased numbers of myeloid-derived suppressor cells (MDSCs) play a diverse role in the pathogenesis of many infections and cancers but their function in COVID-19 remains unclear. To evaluate the function of MDSCs in relation with the severity of COVID-19. 26 PCR-confirmed COVID-19 patients including 12 moderate and 14 severe patients along with 11 healthy age- and sex-matched controls were enrolled. 10 ml whole blood was harvested for cell isolation, immunophenotyping and stimulation. The immunophenotype of MDSCs by flow cytometry and T cells proliferation in the presence of MDSCs was evaluated. Serum TGF-ß was assessed by ELISA. High percentages of M-MDSCs in males and of P-MDSCs in female patients were found in severe and moderate affected patients. Isolated MDSCs of COVID-19 patients suppressed the proliferation and intracellular levels of IFN-γ in T cells despite significant suppression of T regulatory cells but up-regulation of precursor regulatory T cells. Serum analysis shows increased levels of TGF-ß in severe patients compared to moderate and control subjects (HC) (P = 0.003, P < 0.0001, respectively). The frequency of MDSCs in blood shows higher frequency among both moderate and severe patients and may be considered as a predictive factor for disease severity. MDSCs may suppress T cell proliferation by releasing TGF-ß.
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COVID-19 , Células Supressoras Mieloides , Masculino , Humanos , Feminino , Imunofenotipagem , SARS-CoV-2 , Fator de Crescimento Transformador betaRESUMO
Background: Globally, lung cancer represents a major cause of cancer-related deaths. The regulation of gene expression is modulated by small noncoding RNAs called miRNAs that can act as both tumor suppressors and oncogenes. The maturation, expression and binding to target mRNAs is affected by single nucleotide polymorphisms (SNPs) in miRNA genomic regions thereby contributing to cancer susceptibility. SNPs Rs11614913 in miR196a and Rs3746444 in miR-499 are implicated in the development of cancers such as non-small cell lung cancer (NSCLC) in non-Arabic subjects. Materials and Methods: A small cohort of 204 participants including 104 lung cancer patients and 100 non-cancer controls subjects were enrolled into the study. The allele frequencies were determined by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) and their correlation with lung cancer risk was determined. Results: The miR-196a rs11614913 polymorphism increased the risk of NSCLC (CC vs. TT+TC: OR= 2.26, 95%CI= 1.28 - 3.98, P= 0.0046) in a dominant genetic model. No statistically significant association was found between the miR-499 rs37464444 polymorphism and NSCLC. Conclusion: The rs11614913 polymorphism in miR-196a, but not the miR-499 rs37464444 polymorphism, increased the risk of NSCLC. Further studies with larger sample sizes in correlation with functional outcomes at the cellular level should be undertaken.
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Background: The aim of the present study was to investigate the susceptibility of purified protein derivative (PPD) plus health-care workers to SARS-CoV-2 (COVID-19). For this reason, single-nucleotide polymorphism (SNP) of interferon-gamma (IFN-γ) gene at position +2109 and IFN-γ receptor 1 (R1) at position -56 was assessed in PPD plus group before and after COVID-19 infection (2017-2018; 2020-2021). Methods: The selected study cases (n = 100) that were working in tuberculosis (TB) unite (5-10 years) with PPD positivity >15 mm (16-20 mm) were included in this investigation. Sampling was done twice, once before and after the COVID-19 pandemic. Group A contains 50 samples collected from the GenBank TB laboratory that belong to TB staff before the pandemic (2017-2018). The other sample (Group B; 2021) was collected from the same unite during the COVID-19 pandemic. The SNP in the IFN-γ gene (+2109; 670 bp) and IFN-γ R 1 (-56; 366 bp) was performed using a specific primer and the polymerase chain reaction products were digested using restriction enzyme Fau I and Bts I, respectively. Statistical analyses were used to obtain the frequency of alleles among all studied cases. The confidence intervals (CIs) and t-test were calculated using the SPSS and GraphPad Prism software. Results: In overall, the most frequent genotype in Group A was AA (41/50; 82%) and Group B was 76% (38/50) in position + 2109 (odds ratio [OR] = 0.69, 95% CI, 0.26-1.83, and P = 0.46). Although in position -56, the most frequent genotype in Group A was TT (35/50; 70%) which significantly was than Group B TT (15/50; 30%) (OR = 0.184, 95% CI, 0.78-0.43, and P = 0.00). The frequency of allele A was more in both groups at position + 2109 (OR = 0.815, 95% CI, 0.23-2.86, and P = 0.75), whereas the dominate allele at position -56 was T in Group A (OR = 1.37, 95% CI, 0.62-3.02, and P = 0.42). Conclusion: No significant differences were observed in + 2109 in genotype among Group A and B. The main differences were seen in IFN-γ R1 at position (-56) between Group A and B. Hence, the IFN-γ R1 may play important role in COVID-19 infection. However, more study is needed to clear the IFN-γ correlation to COVID-19 infection.
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COVID-19 , Tuberculose , Humanos , Estudos de Casos e Controles , COVID-19/genética , Predisposição Genética para Doença , Genótipo , Interferon gama/genética , Pandemias , Polimorfismo de Nucleotídeo Único , SARS-CoV-2/genética , Tuberculose/genética , Tuberculina , Receptor de Interferon gamaRESUMO
Background: Although many aspects of the COVID-19 disease have not yet been clarified, dysregulation of the immune system may play a crucial role in the progression of the disease. In this study, the lymphocyte subsets were evaluated in patients with different severities of COVID-19. Materials and Methods: In this prospective study, the frequencies of peripheral lymphocyte subsets (CD3+, CD4+, and CD8+ T cells; CD19+ and CD20+ B cells; CD16+/CD56+ NK cells, and CD4+/CD25+/FOXP3+ regulatory T cells) were evaluated in 67 patients with confirmed COVID-19 on the first day of their admission. Results: The mean age of patients was 51.3 ± 14.8 years. Thirty-two patients (47.8%) were classified as severe cases, and 11 (16.4%) were categorized as critical. The frequencies of blood lymphocytes, CD3+ cells, CD25+FOXP3+ T cells, and absolute count of CD3+ T cells, CD25+FOXP3+ T cells, CD4+ T cells, CD8+ T cells, and CD16+56+ lymphocytes were lower in more severe cases compared to the milder patients. The percentages of lymphocytes, T cells, and NK cells were significantly lower in the deceased patients. (p= 0.002 and p= 0.042, p=0.006, respectively). Conclusion: Findings of this cohort study demonstrated that the frequencies of CD4+, CD8+, CD25+FOXP3+ T cells, and NK cells differed in the severe cases of COVID-19. Moreover, lower frequency of T cells and NK cells could be predictors of mortality in these patients.
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Introduction: COVID-19 (coronavirus disease-2019) still causes a high rate of death globally with no definite curative treatment described. The traditional plant Borage (Borago officinalis L.) is a good source of gamma-linolenic (GLA). We hypothesized that Borage plus syrup (BPS) would be beneficial in severe COVID-19 patients within an intensive care unit (ICU) setting. Materials and methods: A pilot single center, randomized trial with no placebo was undertaken. A total of 60 PCR-positive severe COVID-19 participants admitted to ICU from June 2020-December 2020 at Masih Daneshvari Hospital Tehran-Iran gave informed consent. The participants were randomly assigned to either Borage Plus Syrup (BPS, 5 ml for 5 days) (n = 30) or standard care (IFN-ß and favipiravir) as a control group (n = 30). Pao2/Fio2, serum ferritin, CRP, bilirubin, IL-6, TNF-α, ALT, AST, PCT and serum IL-8 was measured upon admission and on release. Results: All the measured parameters decreased significantly with BPS treatment. In the control group, most parameters significantly improved apart from AST and PCT. In addition, the suppression of serum TNF levels in the BPS group was greater than that seen in the control group (P ≤ 0.05). Moreover, the length of ICU stay was significantly lower in the BPS group compared with the control group (P ≤ 0.05). Conclusion: Our study shows that addition of BPS to the standard treatment regime of COVID-19 patients in ICU improved outcomes and reduced the length of ICU treatment. Natural products could be considered as new approaches for reducting the harmful consequences of COVID-19.
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Background: The success of treatment strategies to control the disease relapse requires determining factors affecting the incident short-time and long-time of disease relapse. Therefore, this study was aimed to identify the factors affecting of short-and long-time of occurrence of disease relapse in patients with tuberculosis (TB) using a parametric mixture cure model. Materials and Methods: In this historical cohort study; the data was collected from 4564 patients with TB who referred to the Tuberculosis and Lung Diseases Research Center of Dr. Masih Daneshvari Hospital from 2005 to 2015. In order to evaluate the factors affecting of short-and long-time of occurrence of disease relapse, a parametric mixture cure model was used. Results: In this study, the estimation of the annual incidence of TB relapse showed that the probability of recurrence in the first year is 1% and in the third and tenth years after treatment is 3% and 5%, respectively. In addition, the results of this study showed that the variables of residence, exposure to cigarette smoke, adverse effects of drug use, incarceration, and pulmonary and extra- pulmonary tuberculosis were the factors affecting the short-time recurrence of TB. The variables of drug use, pulmonary and extra- pulmonary tuberculosis, and also incarceration affected the long-term recurrence of this disease. Conclusion: Cure models by separating factors affecting the short-time occurrence from the long-time occurrence of disease relapse can provide more accurate information to researchers to control and reduce TB relapse.
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Aim: To validate a questionnaire to assess stress and burnout in healthcare workers during COVID-19 pandemic. Subjects and methods: In this study, content validity, Cronbach's alpha, and test-retest reliability method were utilized among 60 HCWs to evaluate the validity, internal consistency, and reliability of the questionnaire respectively. The final questionnaire was composed of four parts asking for the background information, questions about the stress caused by the COVID-19, the Depression, Anxiety and Stress Scale - 21 (DASS-21), and six questions from the Copenhagen Burnout Inventory (CBI). Results: The CVR of 46 questions was equal to 1, making them acceptably valid (CVR > 0.78), so that the items could be arranged into a final questionnaire. Moreover, all items could successfully attain CVI values above 0.79, confirming the content validity of the questionnaire. The Cronbach's alpha was between 0.80-0.95 for different sections of questionaire, confirming the stable reliability and high repeatability of the questionnaire. Conclusion: The results of this study showed that the DASS-21 offers adequate levels of validity and reliability for assessing the stress, anxiety, and depression among the HCWs engaged with the COVID-19 pandemic. Moreover, the six items adapted from the Copenhagen burnout inventory (CBI) were found to provide a good instrument for investigating the job burnout among the HCWs at Masih Daneshvari Hospital during the outbreak of the COVID-19 epidemic.