Individual genetic variability mainly of Proinflammatory cytokines, cytokine receptors, and toll-like receptors dictates pathophysiology of COVID-19 disease.

Innate and acquired immunity responses are crucial for viral infection elimination. However, genetic variations in coding genes may exacerbate the inflammation or initiate devastating cytokine storms which poses severe respiratory conditions in coronavirus disease-19 (COVID-19). Host genetic variations in particular those related to the immune responses determine the patients' susceptibility and COVID-19 severity and pathophysiology. Gene polymorphisms such as single nucleotide polymorphisms (SNPs) of interferons, TNF, IL1, IL4, IL6, IL7, IL10, and IL17 predispose patients to the severe form of COVID-19 or severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). These variations mainly alter the gene expression and cause a severe response by B cells, T cells, monocytes, neutrophils, and natural killer cells participating in a cytokine storm. Moreover, cytokines and chemokines SNPs are associated with the severity of COVID-19 and clinical outcomes depending on the corresponding effect. Additionally, genetic variations in genes encoding toll-like receptors (TLRs) mainly TLR3, TLR7, and TLR9 have been related to the COVID-19 severe respiratory symptoms. The specific relation of these mutations with the novel variants of concern (VOCs) infection remains to be elucidated. Genetic variations mainly within genes encoding proinflammatory cytokines, cytokine receptors, and TLRs predispose patients to COVID-19 disease severity. Understanding host immune gene variations associated with the SARS-COV-2 infection opens insights to control the pathophysiology of emerging viral infections.

Evaluation the Possible Role of Interleukin-6 and Tumor Necrosis Factor- Alpha in Pathogenesis of Obstructive Sleep Apnea in Obese Patients: A Case-Control Study:.

BACKGROUND: According to a mounting body of evidence, recent observations have highlighted considerable association between obstructive sleep apnea (OSA) syndrome and patients' obesity and inflammation, however the exact underlying mechanisms remain to be fully understood. In this study, the relationship between OSA and Interleukin-6 and Tumor necrosis factor- alpha was assessed in obese patients and their serum concentrations were compared to non-OSA obese subjects. MATERIALS AND METHODS: This case-control study was conducted on forty-six obese OSA patients (body mass indices, BMI30) and 42 obese but otherwise healthy individuals who were admitted to the pulmonary or obesity clinics of the Hazrat-e Rasool General Hospital (Tehran, Iran) between November 2019 and May 2020 were included. The participants completed the NOSAS, EPWORTH and STOPBANG questionnaires. Tumor Necrosis Factor-Alpha (TNF-α) and Interleukin-6 (IL-6) serum concentrations were determined using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Compared to the non-OSA group, OSA patients had higher systolic and diastolic blood pressure, pCO2, bicarbonate (HCO3) and hemoglobin and lower high-density lipoprotein (HDL) values. IL-6 and TNF-α serum levels were not significantly different between both groups. Univariate and multivariate linear regression models showed that BMI, systolic blood pressure, pCO2 and HCO3 can positively affect the serum TNF-α and systolic blood pressure and HCO3 can also positively affect the serum IL-6 values in patients with the OSA. CONCLUSION: This investigation suggests that among the OSA patients, the heightened inflammatory profile may be influenced by the high BMI. Furthermore, the exclusive relationship between different disease biomarkers and inflammatory agents in OSA patients is intriguing and needs further research.

Adherence to the algorithmic approach for diagnosis of pulmonary embolism: A teaching hospital experience, Shiraz, Iran.

BACKGROUND: We evaluated to see if the algorithmic approach of pulmonary embolism (PE) [Wells' score, followed by D-dimer test and computed tomography pulmonary angiography (CTPA)] is appropriately followed in teaching hospitals of Shiraz, Iran. METHODS: From October 2012 to October 2013, we prospectively calculated Wells' score for all patients who underwent CTPA with clinical suspicion to PE; patients with low probability who had not checked the D-dimer or had low level of D-dimer were considered as non-adherent to the guideline and those with high level of D-dimer or high probability of Wells' score were labeled as adherent to the PE guideline. CTPA scans were independently reported by two radiologists. RESULTS: During study period, 364 patients underwent CTPA to rule out PE, of which 125 (34.3%) had Wells' score > 4 (high probable risk) and 239 had Wells' score ≤ 4. Amongst low probable risk patients (Wells' score ≤ 4), only 32 patients had undergone the D-dimer test (23 patients had high level of D-dimer). Based on the algorithmic approach, patients with suspected PE, patients with high probability (125 patients), and patients with low probability with elevated D-dimer level (23 patients) were considered as adherent to the PE guideline; consequently, the total adherence to PE guideline was 148 out of 364 (40.6%). CONCLUSION: We followed the algorithmic approach guideline in about 40.0% of cases; however, we should pay more attention to the algorithmic approach in patients with suspected PE.