Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) +49A>G (rs231775) gene polymorphism is not associated with COVID-19 severity and mortality in an Iranian population.

Introduction: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulates T cell immune responses as an immune activation inhibitor. Literature reviews suggest that COVID-19 is associated with dysregulation of the inflammatory immune response. The purpose of the present hospital-based case-control study was to evaluate the genetic association of the CTLA4 +49A > G (rs231775) Single Nucleotide Polymorphism (SNP) with COVID-19 severity and mortality among the Iranian people. Method: Genomic DNA of peripheral blood nuclear cells was extracted from the 794 COVID-19 patients and 167 control individuals. The polymorphic site of rs231775 was genotyped using the PCR-RFLP technique. Also, to identify whether this genetic variation was related to CTLA-4 mRNA expression, total RNA was extracted from 178 COVID-19 patients and 70 controls. The mRNA levels of CTLA-4 were determined using real-time PCR. Result: There were no statistically significant differences found in the genotype and allele frequencies among the different genetic models with regards to the severity and mortality of COVID-19. Furthermore, there was no significant association between rs231775 genotypes and CTLA-4 mRNA expression in patients. Conclusion: Our findings demonstrated that SARS-CoV-2 infection is not associated with rs231775 in the Iranian people. More investigations are crucial to show how this genetic variation affects other ethnic groups. Given the importance of CTLA-4 in regulating immune responses, further studies are recommended to examine other CTLA-4 SNPs and the function of this gene in COVID-19 patients.

Comparison of culture and PCR-DGGE methods to evaluate the airways of cystic fibrosis patients and determination of their antibiotic resistance profile.

Background and Objectives: Respiratory infections are the most serious condition in cystic fibrosis (CF) patients; therefore, a thorough comprehension of the diversity and dominant microbial species in CF airways has a crucial role in treatment. Our objective was to determine the antibiotic resistance profile of CF airways microbiota and compare culture methods and PCR-DGGE to evaluate bacterial diversity. Materials and Methods: Pharyngeal swabs from 121 CF patients were collected. The samples were then cultured, identified and antibiotic resistance testing was performed. Thirty samples were subjected to further molecular surveys. DNA contents of these samples were extracted and amplified using nested-PCR technique and their bacterial diversity was assessed by DGGE. The DGGE patterns were visualized and certain bands were excised and purified. Next, the DNA was amplified by another round of PCR and sent out for sequencing. Results: Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the most prevalent species isolated using culture methods. S. aureus was the most common bacteria among 6 years and younger patients; while, P. aeruginosa had more prevalence among older ones. The PCR-DGGE results showed more diversity than culture methods, particularly in younger patients who exhibited more bacterial diversity than the older groups. Sequencing results unveiled the presence of certain bacterial species including Haemophilus parainfluenzae and Stenotrophomonas maltophilia which were completely missed in culture. Conclusion: Even though culture-dependent methods are cost-effective, PCR-DGGE appeared to be more efficient to determine bacterial diversity. PCR-DGGE detects less abundant species, though their viability could not be determined using this method.

Relationship Between Dairy Intake and Hospitalization Risk and Disease Severity in Patients With COVID-19.

The aim of this study was to investigate whether dairy intake was associated with the severity of coronavirus disease 2019 (COVID-19) disease and the probability of hospitalization of patients. This cross-sectional study was conducted on 141 patients with COVID-19 with an average age of 46.23 ± 15.88 years. The number of men (52.5%) participating in this study was higher than that of women. The association between dairy intake and COVID-19 was evaluated by multivariable logistic regression analysis. The risk of hospitalization in the highest tertile of dairy intake was 31% lower than in the lowest tertile (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.37-1.25, p trend = 0.023). Higher milk and yogurt intake was associated with a reduced risk of hospitalization due to COVID-19. Patients in the third tertiles were about 65% (p for trend = 0.014) and 12% (p for trend = 0.050) less likely to be hospitalized than those in the first tertile, respectively. Dairy consumption, especially low-fat ones, was associated with a lower risk of hospitalization due to COVID-19 and lower severity of COVID-19.

Chemical exposure and alveolar macrophages responses: 'the role of pulmonary defense mechanism in inhalation injuries'.

Epidemiological and clinical studies have indicated an association between particulate matter (PM) exposure and acute and chronic pulmonary inflammation, which may be registered as increased mortality and morbidity. Despite the increasing evidence, the pathophysiology mechanism of these PMs is still not fully characterised. Pulmonary alveolar macrophages (PAMs), as a predominant cell in the lung, play a critically important role in these pathological mechanisms. Toxin exposure triggers events associated with macrophage activation, including oxidative stress, acute damage, tissue disruption, remodelling and fibrosis. Targeting macrophage may potentially be employed to treat these types of lung inflammation without affecting the natural immune response to bacterial infections. Biological toxins, their sources of exposure, physical and other properties, and their effects on the individuals are summarised in this article. Inhaled particulates from air pollution and toxic gases containing chemicals can interact with alveolar epithelial cells and immune cells in the airways. PAMs can sense ambient pollutants and be stimulated, triggering cellular signalling pathways. These cells are highly adaptable and can change their function and phenotype in response to inhaled agents. PAMs also have the ability to polarise and undergo plasticity in response to tissue damage, while maintaining resistance to exposure to inhaled agents.

Effect of tofacitinib on clinical and laboratory findings in severe and resistant patients with COVID-19.

BACKGROUND: The efficacy and safety of a strong Janus kinase inhibitor, tofacitinib, in individuals suffering from severe coronavirus disease 2019 (Covid-19) pneumonia are not definite well. METHODS: In this non-randomized and non-blinded trial, a total of 52 Iranian patients with severe COVID-19 associated with decreased oxygen saturation, elevated C-reactive protein, and/or persistent fever were included. A total of 52 patients were included in this study. Tofacitinib was administered to 29 patients (55.8%) in addition to the standard care treatments, whereas 23 patients (44.2%) were treated with the standard of care alone (mostly antiviral agents and corticosteroids). Tofacitinib was administered at a dose of 5 mg twice daily for up to 10 days. The primary outcomes were mortality rate, oxygen saturation level, CT findings, rate of breath, heart rate, and level of consciousness. Inflammatory cytokines and blood biomarkers were considered as the secondary outcomes. RESULTS: Death from any cause through day 14 occurred in 51.7% of the tofacitinib group and 65.2% of the control group. There was no significant difference in lung radiographic findings between the intervention and control groups at the first day of the study and after the study period. However, a significant decrease was observed in the extent of lung tissue involvement in the intervention group after administration of tofacitinib. Regarding cell and blood biomarkers, a significant decrease in the CPK levels in the intervention group and Hct and ACE levels in the control group was observed after fourteen days of the study. Moreover, a significant increase in SGOT and ferritin values was detected in the control group 14 days after the beginning tofacitinib administration. Comparing control and intervention groups, there was a significant difference in hemoglobin, SGOT, LDH, ferritin, and ACE values between groups before the intervention, while after fourteen days of the study, no significant difference was found. In case of DHEAS and TSH levels, a significant decrease was seen in the intervention group compared to the control after the study period. No other significant improvement was detected in other outcomes of the tofacitinib group compared to the control. CONCLUSIONS: The administration of tofacitinib combined with corticosteroids, is not effective enough to treat severe COVID-19 patients and the use of this medication should be considered before the disease deterioration.

Impact of the MCP-1-2518A>G polymorphism on COVID-19 severity in the Iranian population: A case-control study.

As a result of SARS-CoV-2 infection, the host's immune system is disrupted, and chemokines and cytokines are intensified to eliminate the virus, resulting in cytokine storm syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19 have been observed to have elevated levels of MCP-1, a chemokine associated with the severity of the disease. In some diseases, polymorphisms in the regulatory region of the MCP-1 gene correspond to serum levels and disease severity. An attempt was made in this study to assess the relationship between MCP-1 G-2518A and serum MCP-1 levels in Iranian COVID-19 patients and the severity of the disease. In this study, patients were randomly sampled from outpatients on the first day of diagnosis and from inpatients on the first day of their hospitalization. Patients were classified into the outpatient (without symptoms or with mild symptoms) and inpatient (with moderate, severe, and critical symptoms) groups. The serum level of MCP-1 was measured by ELISA and the frequency of MCP-1 G-2518A gene polymorphism genotypes in COVID-19 patients was checked by the RFLP-PCR method. Participants with COVID-19 infection had a higher rate of underlying diseases, such as diabetes, high blood pressure, kidney disease, and cardiovascular disease than the control group (P-value < 0.001). Also, the frequency of these factors in inpatients was significantly higher compared to outpatients (P-value < 0.001). Additionally, the level of MCP-1 in serum was significantly different with an average of 11.90 in comparison to 2.98 in the control group (P-value, 0.05), which is attributed to elevated serum levels among patients in hospitals with an average of 11.72 in comparison to 2.98 in the control group. Compared with outpatients, inpatients had a higher frequency of the G allele of the MCP-1-2518 polymorphism (P-value < 0.05), while a notable difference was observed in the serum level of MCP-1 in COVID-19 patients with the MCP-1-2518 AA genotype in the whole group in comparison to the control group (P-value: 0.024). Totally, the results showed that a high frequency of the G allele is related to hospitalization and poor outcome in COVID-19 cases.

Association of programmed cell death 1 (PD-1) gene polymorphism (rs10204525) with COVID-19 severity and mortality: A case-control study in the Iranian population.

BACKGROUND: Programmed cell death 1 (PD-1), as a negative immune regulator, regulates the activation of T cells and maintains the immune system's homeostasis. Previous studies suggest that the effective immune response against COVID-19 contributes to the outcome of the disease. The present study aims to evaluate whether the PD-1 rs10204525 polymorphism is associated with PDCD-1 expression and COVID-19 severity and mortality in the Iranian population. METHODS: The PD-1 rs10204525 was genotyped in 810 COVID-19 patients and 164 healthy individuals as a control group using Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Moreover, we assessed the expression of PDCD-1 in peripheral blood nuclear cells by real-time PCR. RESULTS: Regarding disease severity and mortality, no significant differences were detected between study groups in alleles and genotypes frequency distribution under different inheritance models. We found that the expression of PDCD-1 was significantly lower in COVID-19 patients with AG and GG genotypes than in the control group. Regarding disease severity, mRNA levels of PDCD-1 were significantly lower in moderate and critical patients carrying AG genotype than in control (P = 0.005 and P = 0.002, respectively) and mild (P = 0.014 and P = 0.005, respectively) individuals. Additionally, the severe and critical patients with GG genotype displayed a significantly lower level of PDCD-1 compared with the control (P = 0.002 and P < 0.001, respectively), mild (P = 0.004 and P < 0.001, respectively), and moderate (P = 0.014 and P < 0.001, respectively) ones. Regarding disease mortality, the expression of PDCD-1 was significantly lower in non-survivor COVID-19 patients with GG genotype than in survivors. CONCLUSION: Considering the lack of significant differences in PDCD-1 expression in different genotypes in the control group, lower expression of PDCD-1 in COVID-19 patients carrying the G allele suggests the impact of this single-nucleotide polymorphism on the transcriptional activity of PD-1.

The association of dietary approach to stop hypertension (DASH) diet with hospitalization risk in patients with COVID-19.

Background and aim: Given the importance of dietary habits in the immune system, the current study aimed at investigating the association between Dietary Approach to Stop Hypertension (DASH) diet and risk of hospitalization due to COVID-19. Methods: Dietary data of 141 patients with COVID-19 were collected using 147-item food frequency questionnaire. DASH score in this cross-sectional study was calculated based on eight components, including fruits, vegetables, legumes and nuts and seeds, whole grains, low-fat dairy, red or processed meats, sweetened beverages, and sodium. Multivariable logistic regression models were applied to estimate the OR and 95% CI for hospitalization due to COVID-19 in each tertile of DASH score. Results: Mean ± SD of DASH score in inpatients (n=74) and outpatients (n= 87) was 22.5 ± 4.57 and 25.34 ± 4.23, respectively. The risk of hospitalization in the highest tertile of DASH score was 81% lower than the lowest tertile (OR=0.19, 95%CI: 0.07-0.55, P trend = 0.001 after adjustment for age, sex, BMI, energy intake). Also, more intake of fruits, vegetables and low-fat dairy products and less intake of sodium, red and processed meat were each significantly associated with reduced risk of hospitalization due to COVID-19. Conclusions: Our data provide evidence that adherence to DASH-style diet was associated with lower risk of hospitalization due to COVID-19.

Is COVID-19 severity unrelated to antinuclear antibodies?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces an overreaction of the immune system, resulting in the production of auto-antibodies. Several studies have reported that autoantibodies are prevalent in COVID-19 patients. In our study, antinuclear antibodies were evaluated in patients with COVID-19. We examined 131 sera from patients (>17-year-old) with confirmed COVID-19. Samples were collected prior to receiving any medication and antinuclear antibodies (ANA) levels were measured by the indirect immunofluorescence (IIF) method. Furthermore, the immunoblotting test was used to determine the presence of anti-nuclear antigen antibodies. The IIF-ANA test was positive in 36.4% (48/131) of patients. Overall, non-ICU patients had higher IIF-ANA titers than ICU patients. In particular, ICU patients had fewer nuclear, cytoplasmic, and mitotic IIF-ANA antibodies than non-ICU patients. In conclusion, COVID-19 patients frequently have ANA possibly reflecting the immune dysregulation due to several damaged cells by SARS-CoV-2 virus.

Changes in hormones, Leukocyte Telomere Length (LTL), and p16INK4a expression in SM-exposed individuals in favor of the cellular senescence.

Sulfur mustard (SM) is a chemical warfare agent with well-known severe toxic effects and may cause long-term debilitating injuries. We aimed to evaluate aging and longevity in Iranian SM-exposed survivors using some endocrine and molecular biomarkers for the first time. Dehydroepiandrosterone (DHEA), prolactin (PRL), cortisol, testosterone, and luteinizing hormone (LH) were measured in 289 male SM-veterans and 66 age-matched males using the ELISA method. Leukocyte Telomere Length (LTL) measurement and p16INK4a expression were measured in the peripheral blood leukocytes of 55 males who were exposed to SM. We found a significantly lower serum DHEAS level and higher serum PRL level in SM-exposed groups (without any related to the severity of lung injuries) compared to healthy controls, but no significant difference in serum levels of cortisol, testosterone, and LH. The molar ratio of DHEAS/cortisol was significantly higher in controls compared to the SM-exposed individuals especially those with severe lung damage. Some biological parameters of allostatic load score such as DHEAS and DHEAS/cortisol ratio significantly decreased long-term after the SM exposure. Additionally, we found that LTL was shorter in SM-exposed veterans rather than unexposed controls while p16INK4a gene expression significantly increased in these groups. It seems that DHEAS, DHEAS/cortisol ratio, LTL, and p16INK4a gene expression have changed significantly in favor of cellular senescence in SM-exposed patients. Therefore, it seems that SM exposure increases biological age compared to chronological age in SM-exposed survivors.

Increased serum lipofuscin associated with leukocyte telomere shortening in veterans: a possible role for sulfur mustard exposure in delayed-onset accelerated cellular senescence.

BACKGROUND: Sulfur mustard (SM) is a toxic gas that causes chronic inflammation and oxidative stress leading to cell senescence. This study aimed to evaluate two indicators of biological aging (i.e., serum lipofuscin level and leukocyte telomere length) and assess their relationship based on the severity of SM exposure in the long term. METHODS: The study was performed on two groups of male participants. 1) SM-exposed group (exposed to SM once in 1987), 73 volunteers. 2) Non-exposed group, 16 healthy volunteers. The SM-exposed group was categorized into three subgroups based on the severity of SM exposure and body damage (asymptom, mild, and severe). The blood sample was prepared from members of each group. The serum lipofuscin, TGF-ß, malondialdehyde (MDA), c-reactive protein (CRP), and leukocyte telomere length (TL) were measured in all participants. RESULTS: The MDA level was increased in the SM-exposed group (mean = 39.6 µM, SD = 16.5) compared to the non-exposed group (mean = 21.1 µM, SD = 10.3) (P < 0.05). The CRP level was also increased in the SM-exposed group (mean = 5.12 mg/l, SD = 3.36) compared to the non-exposed group (mean = 3.51 mg/l, SD = 1.21), while the TGF-ß level was decreased (P < 0.05) in the SM-exposed group (mean = 52.6 pg/ml, SD = 18.7) compared to the non-exposed group (mean = 68.9 pg/ml, SD = 13.8). The relative TL was shorter in the SM-exposed group (mean = 0.40, SD = 0.28) than in the non-exposed group (mean = 2.25, SD = 1.41) (P < 0.05). The lipofuscin level was higher in the total SM-exposed group (mean = 1.44 ng/ml, SD = 0.685) than in the non-exposed group (mean = 0.88 ng/ml, SD = 0.449) (P < 0.05). The MDA and CRP levels were increased in the SM-exposed subgroups of asymptom, mild, and severe than the non-exposed group, while TGF-ß level and TL were decreased in those subgroups. The lipofuscin level was higher in the SM-exposed subgroups of mild and severe than in the non-exposed group. The regression analysis determined a negative correlation between lipofuscin level and TL. The lipofuscin/TL ratio was higher in the total SM-exposed group (mean = 6.36, SD = 5.342) than in the non-exposed group (mean = 0.51, SD=0.389). This ratio was also higher in the SM-exposed subgroups of asymptom, mild, and severe than in the non-exposed group. The lipofuscin/TL ratio did not differ between mild and severe subgroups. CONCLUSION: The delayed toxicity of SM is associated with chronic oxidative stress, continuous inflammatory stimulation, increased lipofuscin, and telomere shortening. Future studies are needed to verify the suitability of serum lipofuscin to telomere length ratio in determining the severity of SM toxicity.

Immunophenotyping characteristics of COVID-19 patients: Peripheral blood CD8+ HLA-DR+ T cells as a biomarker for mortality outcome.

INTRODUCTION: The goal of this study was to identify biomarker(s) to assign risk of mortality in COVID-19 patients to improve intensive care unit (ICU) and coronary care unit  management. A total of 100 confirmed COVID-19 patients admitted at Imam Khomeini Hospital in Tehran, were compared to 70 control subjects. Peripheral blood leukocyte was studied using staining reagents included CD3, CD4, CD8, HLA-DR, CD19, CD16, and CD56. The immunophenotyping analysis was evaluated using the FACSCalibur instrument. To investigate the cell density of lung infiltrating T cells, postmortem slides of needle necropsies taken from the lung tissue of 3 critical patients were evaluated by immunohistochemistry staining. The number of lymphocyte subpopulations was significantly lower in COVID-19 patients than in the control group. Regarding the disease severity, the absolute count of T, NK, and HLA-DR+ T cells were significantly reduced in severe patients compared to the moderate ones. The critical patients had a significantly lower count of CD8-HLA-DR+ T cells than the moderate cases. Regarding the disease mortality, based on univariate analysis, the count of HLA-DR+ T, CD8- HLA-DR+ T, and CD8+ HLA-DR+ T cells was associated with mortality in COVID-19 patients. Receiver operating characteristic curve analysis showed the count of CD8+ HLA-DR+ T cells is the best candidate as a biomarker for mortality outcome. Furthermore, pulmonary infiltration of T cells in the lung tissue showed only slight infiltrations of CD3+ T cells, with an equal percentage of CD4+ and CD8+ T cell subpopulation in the lung tissue. These findings suggest that close monitoring of the value of CD8+ HLA-DR+ T cells in COVID-19 patients may be helpful to identify high-risk patients. However, further studies with larger sample size are needed.

Plant-based diet and COVID-19 severity: results from a cross-sectional study.

Although previous findings have shown the beneficial role of healthy eating pattern on the human immune system, the association between plant-based diet and COVID-19 severity has not yet been elucidated. This study aimed to determine the possible role of plant-based diet index (PDI) in COVID-19 severity. This cross-sectional, multicentral study was conducted on 141 patients with confirmed COVID-19. Dietary intakes of the patients were evaluated using a validated food frequency questionnaire. Then, PDI was compared between patients who needed to be hospitalised (considered severe cases), and those who got treatment at home (considered non-severe cases). After adjustment for confounders including age, sex, energy intake and body mass index, lower odds of hospitalisation were found for participants having a greater score of overall PDI (OR per 10 units increase: 0.42; 95% CI 0.22 to 0.80) and healthy PDI (OR per 10 unit increase: 0.45; 95% CI 0.26 to 0.78). In conclusion, our data presented that there is a relation between PDI and lower risk of hospitalisation in COVID-19 patients, possibly through boosting the immune function.

Pseudomonas aeruginosa PAO1 outer membrane vesicles-diphtheria toxoid conjugate as a vaccine candidate in a murine burn model.

Pseudomonas aeruginosa is an opportunistic pathogen considered a common cause of nosocomial infection with high morbidity and mortality in burn patients. Immunoprophylaxis techniques may lower the mortality rate of patients with burn wounds infected by P. aeruginosa; consequently, this may be an efficient strategy to manage infections caused by this bacterium. Several pathogenic Gram-negative bacteria like P. aeruginosa release outer membrane vesicles (OMVs), and structurally OMV consists of several antigenic components capable of generating a wide range of immune responses. Here, we evaluated the immunogenicity and efficacy of P. aeruginosa PA-OMVs (PA-OMVs) conjugated with the diphtheria toxoid (DT) formulated with alum adjuvant (PA-OMVs-DT + adj) in a mice model of burn wound infection. ELISA results showed that in the group of mice immunized with PA-OMVs-DT + adj conjugated, there was a significant increase in specific antibodies titer compared to non-conjugated PA-OMVs or control groups. In addition, the vaccination of mice with PA-OMVs-DT + adj conjugated generated greater protective effectiveness, as seen by lower bacterial loads, and eightfold decreased inflammatory cell infiltration with less tissue damage in the mice burn model compared to the control group. The opsonophagocytic killing results confirmed that humoral immune response might be critical for PA-OMVs mediated protection. These findings suggest that PA-OMV-DT conjugated might be used as a new vaccine against P. aeruginosa in burn wound infection.

Molecular mimicry, hyperactive immune system, and SARS-COV-2 are three prerequisites of the autoimmune disease triangle following COVID-19 infection.

SARS-CoV-2 infection can produce a variety of clinical manifestations, which are either directly related to viral tissue damage or indirectly induced by the antiviral immune response. Molecular mimicry enables this virus to undermine self-tolerance in a host's immune system also immune system's attempts to eliminate SARS-COV-2 may trigger autoimmunity by hyper-activating the innate and adaptive immune systems. Auto immune diseases include Systemic lupus erythematosus, autoimmune thyroid diseases, Guillain-Barre syndrome, Immune thrombocytopenic purpura, and the detection of autoantibodies are the cues to the discovery of the potential of COVID-19 in inducing autoimmunity. As COVID-19 and autoimmune diseases share a common pathogenesis, autoimmune drugs may be an effective treatment option. Susceptible patients must be monitored for autoimmune symptoms after contracting CVID-19. In light of the SARS-COV-2 virus' ability to induce autoimmunity in susceptible patients, will the various COVID-19 vaccines that are the only way to end the pandemic induce autoimmunity?

The role of ACE1 I/D and ACE2 polymorphism in the outcome of Iranian COVID-19 patients: A case-control study.

Background: Since the beginning of the pandemic of coronavirus disease 2019 (COVID-19), many countries have experienced a considerable number of COVID-19 cases and deaths. The etiology of a broad spectrum of symptoms is still debated. Host genetic variants might also significantly influence the outcome of the disease. This study aimed to evaluate the association of angiotensin-converting enzyme (ACE1) gene Insertion/Deletion (I/D) polymorphism (rs1799752) and ACE2 gene rs1978124 single nucleotide polymorphism with the COVID-19 severity. Methods: This study was conducted on 470 COVID-19 patients and a control group of 56 healthy individuals across several major cities in Iran. The blood sample and clinical data were collected from the participants, and their ACE1 I/D and ACE2 rs1978124 polymorphisms were determined using polymerase chain reaction and PCR-RFLP, respectively. Serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and ACE1 were measured in the blood samples. Results: We found that the ACE1 DD genotype frequency was inversely correlated with the risk of intubation (p = 0.017) and mortality in COVID-19 patients (p = 0.049). Even after adjustment, logistic regression demonstrated that this significant inverse association remained constant for the above variables at odds ratios of (OR) = 0.35 and Odds Ratio = 0.49, respectively. Also, in the expired (p = 0.042) and intubated (p = 0.048) groups with II + ID genotypes, the mean level of CRP was significantly higher than in the DD genotype group. Furthermore, in both intubated and expired groups, the mean serum level of ACE1 was higher compared with non-intubated and survived groups with II or II + ID genotypes. The results also indicated that ACE2 rs1978124 TT + CT genotypes in females have a significant positive role in susceptibility to COVID-19; however, in females, the TT + CT genotypes had a protective effect (OR = 0.098) against the severity of COVID-19. Conclusion: These findings suggest that ACE1 I/D and ACE2 rs1978124 polymorphism could potentially influence the outcome of COVID-19 in the Iranian population.

Cytokine patterns in cystic fibrosis patients with different microbial infections in oropharyngeal samples.

BACKGROUND: Cytokines play a crucial role in the immune system's regulation by mediating protective responses to infections. anti-inflammatory and pro-inflammatory cytokines are in equilibrium. Therefore, any alteration in cytokine production or cytokine receptor expression might result in pathological illnesses and health issues. Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane regulator (CFTR) gene. Lung infection in these patients is related to chronic bacterial airway infection and inflammation, which is triggered by some inflammatory cytokines. Our goal was to compare the cytokine patterns in CF patient's serum and PBMCs caused by microbial pathogens that colonized their airways to controls. METHODS: ELISA and Real-time PCR were used to determine the levels of IL-10, IFN-γ, IL-4, TGF-ß, IL-8, and IL-17 in serum and PBMC cells. Blood parameters in both patients and healthy people were studied. RESULTS: An increase in IL-10, IFN-γ, IL-4 (p-v = 0.03, 0.024 and 0.003) levels and a decrease in IL-17 (p-v = 0.004) was found in Pseudomonas aeruginosa positive patients. There were no different in TGF-ß and IL-8 (p-value = 0.778 and 0.903) in this patients. IL-10, IFN-γ, and IL-4 (p-value = 0.023, 0.001 and 0.002) levels were high in Staphylococcus aureus positive patients and TGF-ß, IL-17, and IL-8 (p-value = 0.085, 0.167 and 0.362) were not significantly different in the patient and control groups. IFN-γ and IL-4 levels were higher in patients without infection who had normal microbiota (p-v = 0.002 and 0.024). In patients with P. aeruginosa, WBC and platelets increased, and MCH and MCV decreased. Patients with normal microbiota had less MCV. CONCLUSION: According to our research, patients with P. aeruginosa, S. aureus, and normal microbiota are exposed to cytokine alterations and changes in blood factors. The link between the CF patient's airway microbiota and the kind of generated cytokines might lead to the modulation of inflammatory cytokines alone or in combination with antibiotics, reducing disease-causing effects while avoiding drug resistance.

Neutrophil to Lymphocyte Ratio (NLR) and Derived NLR Combination: A Cost-effective Predictor of Moderate to Severe COVID-19 Progression.

Inflammation is an essential contributor to Coronavirus disease 2019 (COVID-19).   In this regard, finding a prognostic indicator is valuable because the treatment will be more effective if critical patients with high inflammation are diagnosed earlier. We aimed to evaluate some hematologic markers for COVID-19 and assess their association with the severity of the disease. A total of 154 COVID-19 patients were laboratory-confirmed and admitted to Imam Khomeini Hospital Complex, Tehran, Iran, from February 12, 2020, to April 4, 2020, and 55 healthy individuals were enrolled in the study. The severity of the patients' illnesses was classified into three subgroups according to the types of oxygen therapies (moderate (61), severe (28), and critical (43)) and examined the different ratios of total white blood cell (WBC) count, neutrophil to lymphocyte ratio (NLR), platelet to monocyte ratio (PLR), macrophage to lymphocyte ratio (MLR), derived NLR ratio (dNLR), and some biochemical tests. COVID-19 patients had higher levels of NLR, MLR, PLR, and dNLR than healthy subjects. receiver operating characteristic (ROC) analysis of the curve revealed that NLR and dNLR had a high diagnostic value to differentiate COVID-19 patients from healthy subjects (area under the curve [AUC]=0.923 and 0.910, respectively) and predict mortality (AUC=0.726 and 0.735, respectively). NLR and dNLR may be reliable markers to evaluate the severity of COVID-19. NLR and dNLR had a high diagnostic value for differentiating COVID-19 patients from healthy subjects, and they could predict the severity and outcome of the disease.

Concomitant use of relative telomere length, biological health score and physical/social statuses in the biological aging evaluation of mustard-chemical veterans.

Sulfur mustard (SM) is a toxic gas that has been used as a chemical weapon in wars. After many years, SM-exposed people are still suffering from its side effects such as biological and premature aging. This study was aimed to evaluate biological aging rate via involving biological health scoring (BHS), relative telomere length (TL) and different physical/social variables i.e. marital and smoking statuses, body mass index, salary and educational levels. BHS was calculated according to measurement of 18 biomarkers related to function of four physiological systems (endocrine, inflammatory, cardiovascular and metabolic systems) and two organs (liver and kidney). The volunteers were 442 individuals exposed to SM gas in 1987 and 119 healthy individuals as non-exposed group. Each group was divided based on leukocyte relative TL (short, intermediate and long). Our data showed an inverse correlation between BHS and relative TL in two groups. The BHS was significantly higher in SM-exposed group than non-exposed group, especially in the participants with short and intermediate TL. The BHS had also a positive correlation with smoking and BMI parameters, and a negative correlation with salary and educational levels in the participants with shorter telomeres; and SM strengthened these correlations in the shorter telomeres. It is concluded that the higher BHS along with shorter relative TL that are indices for lower health quality and biological aging, could be used in the health evaluation of non- and SM-exposed people; and involving of BHS, TL and physical/social covariates could be useful to make this evaluation more accurate.

Myositis autoantibodies in Iranian myositis patients: assessment the frequency and clinical relevancy.

INTRODUCTION: Dermatomyositis (DM) and polymyositis (PM) are known as two major types of idiopathic inflammatory myopathies (IMMs). During the past years, growing data strongly suggest the clinical significance of myositis-associated autoantibodies (MAAs) and myositis-specific autoantibodies (MSAs). The present study aimed to determine the profile of MSAs and MAAs, subsequently to address the clinical significance of these autoantibodies in Iranian myositis patients. METHODOLOGY: In this cross-sectional study, 28 DM and 24 PM patients were entered. Demographic and clinical characteristics were collected by direct examination and patients' medical record. The existence of MSAs and MAAs was assessed by indirect immunofluorescence then using immunoblotting (FA 1510-1005-1, DL 1530-1601-4 G; Euroimmun, Germany). Data were analyzed using the SPSS software (v22; SPSS Inc. Chicago, IL, USA). RESULTS: The mean age of the patients was 46.18 ± 12.95 years and male/female ratio was 28.8/71.2. Autoantibodies were positive in 63.46% of myositis patients. Interestingly, anti-TIF1γ and anti-PL7 were significantly associated with malignancy (P < 0.001, P = 0.008; respectively). The existence of autoantibody and anti-Jo1 had significant relation with interstitial lung disease (ILD) (P = 0.034, P = 0.006; respectively). Joint involvements including arthritis and arthralgia were significantly associated with anti-Ro52 and anti-Jo1 (P = 0.04, P = 0.02; respectively). CONCLUSION: Taken together, it can be concluded that certain myositis autoantibodies present clinical significance which is in line with the literature. The use of these autoantibodies as biomarkers by line blotting along with indirect immunofluorescence facilitates diagnosis of inflammatory myopathies and makes it more accurate as well as better management of myositis patients if used based on a science-based manner. Key Points • Identification of MSAs and MAAs facilitates the diagnosis of inflammatory myopathies and provides better myositis patient's management if used according to a science-based manner. • Anti-rod and ring antibody was detected in a patient with ovarian cancer-induced dermatomyositis. • Malignancy and ILD are integrated parts of myositis which can be associated with MSAs and MAAs.