Alternations in miR-155 and miR-200 serum levels can serve as biomarkers for COVID-19 in the post-mass vaccination era.

BACKGROUND: Mass vaccination and natural immunity reduced the severity of COVID-19 cases. SARS-CoV-2 ongoing genome variations imply the use of confirmatory serologic biomarkers besides PCR for reliable diagnosis. MicroRNA molecules are intrinsic components of the innate immune system. The expression of miR155-5p and miR200c-3p was previously correlated with SARS-CoV-2 pathogenesis. This case-control study was conducted during the third peak of the COVID-19 pandemic in Egypt and aimed to calculate the accuracy of miR155-5p and miR200c-3p as biomarkers for COVID-19. METHODS AND RESULTS: Thirty out of 400 COVID-19 patients at a main University hospital in Alexandria were included in the study along with 20 age-matched healthy controls. Plasma samples were collected for total and differential CBC. Relative quantitation of miR155-5p and miR200c-3p expression from WBCs was done by RT-qPCR. The expression of miR155-5p and miR200c-3p was positively correlated and was significantly downregulated in COVID-19 patients compared to the healthy control group (p ˂ 0.005). Both miR155-5p and miR200c-3p were of 76% and 74% accuracy as diagnostic biomarkers of COVID-19, respectively. Regarding the differentiation between mild and moderate cases, their accuracy was 80% and 70%, respectively. CONCLUSIONS: miR155-5p and miR200c-3p expression can be used to confirm the diagnosis of COVID-19 and discriminate between mild and moderate cases, with a moderate degree of accuracy.

SNP (A > G - rs13057211) but not GT(n) polymorphism in HMOX-1 promotor gene is associated with COVID-19 mortality.

INTRODUCTION: COVID-19 causes severe inflammatory respiratory distress syndrome. The global pandemic caused millions of cases of morbidity and mortality worldwide. Patients may present with variable symptoms including dyspnea, fever, and GIT manifestations. The HMOX-1 gene is located on the long (q) arm of chromosome 22 at position 12.3. HMOX-1 is expressed in all mammalian tissues at basal levels and is considered as a stress response enzyme. HMOX-1 has a specific polymorphic site with variable GT(n) repeats at the promotor region. Several authors evaluated the HMOX-1 GT(n) promoter polymorphism in different inflammatory conditions. We evaluated HMOX-1 promoter polymorphism in relation to serum Hemoxygenase level and inflammatory makers (CRP, Ferritin, PCT, IL-6 and D-dimer) in patients affected by SARS-COV-2 disease. SUBJECTS AND METHODS: Ninety patients confirmed to be infected with COVID-19 were followed up till the study end point (recovery and discharge or death). HMOX-1 promotor GT(n) polymorphism was evaluated using Sanger sequencing. HMOX-1 enzyme serum level was measured by ELISA and the level of different inflammatory markers was assessed by available commercial kits. RESULTS: A novel Single nucleotide polymorphism (SNP) (A > G) - rs13057211 in the GT(n) region of HMOX-1 promoter gene was found in 40 (61.5%) COVID-19 patients out of the studied 65 patients. This (A > G) SNP was associated with higher mortality rate in COVID-19 as it was detected in 27 patients (75% of the patients who succumbed to the disease) (p = 0.021, Odds ratio = 3.7; 95% CI:1.29-10.56). Serum IL-6 (Interleuken-6) was positively correlated the length of Hospital Stay (LOHS) and procalcitonin (PCT); (p = 0.014, r: 0.651 and p < 0.001, r:0.997) respectively while negatively correlated with levels of HMOX-1 enzyme serum level (p = 0.013, r: -0.61). CRP correlated positively with LOHS (p = 0.021, r = 0.4), PCT (p = 0.044, r = 0.425) and age (p < 0.001, r = 0.685). Higher levels of D-Dimer and PCT were observed in patients with the long repeat. There was no significant difference between patients who recovered and those who died from COVID-19 as regards HMOX-1 level and GT(n) polymorphism. CONCLUSION: We report a novel SNP (A > G, rs13057211) in the GT(n) region of HMOX-1 promoter gene that was associated with mortality in COVID-19 patients, however no significant difference was found in HMOX-1 serum level or HMOX-1 (GT)n repeats within the studied groups.

Efficacy and safety of inhaled heparin in asthmatic and chronic obstructive pulmonary disease patients: a systematic review and a meta-analysis.

Asthma and chronic obstructive pulmonary disease (COPD) are prevalent chronic respiratory disorders that cause significant morbidity and mortality. Some studies evaluated the use of inhaled unfractionated heparin (UFH) in the treatment of asthma and COPD. We aimed to synthesize the available evidence for the efficacy and safety of inhaled heparin in improving lung functions among asthmatic and COPD patients. A comprehensive search was performed using Pubmed, Embase, EBSCO, Scopus, Web of Science, Cochrane CENTRAL, WHO Clinical trials, clinicaltrials.gov, Iranian Clinical trials, Google Scholar, Research Gate, ProQuest Thesis, OVID, and medRxiv databases. Two independent reviewers included all pertinent articles according to PRISMA guidelines, and extract data independently. The two reviewers checked the quality of studies using the ROB2 tool. To determine the pooled effect estimate of the efficacy and safety of inhaled heparin, a meta-analysis was carried out using the R programming language. Publication bias was evaluated using Egger's regression test. The heterogeneity was explained using a meta-regression, and the quality of evidence was assessed by the GRADE approach. Twenty-six studies with a total of 581 patients were included in the qualitative analysis and 16 in the meta-analysis. The primary outcome was treatment success (improvement of lung function) that was measured by standardized mean differences (SMD) of the forced expiratory volume per second (FEV1) either per ml or percentage. Heparin has a large effect on both FEV1% and FEV1 ml when compared to the control group (SMD 2.7, 95% CI 1.00; 4.39; GRADE high, SMD 2.12, 95% CI - 1.49; 5.72: GRADE moderate, respectively). Secondary outcomes are other lung functions improving parameters such as PC20 (SMD 0.91, 95% CI - 0.15; 1.96). Meta-regression and subgroup analysis show that heparin type, dose, year of publication, study design, and quality of studies had a substantial effect. Regarding safety, inhaled heparin showed a good coagulation profile and mild tolerable side effects. Inhaled heparin showed improvement in lung functions either alone or when added to standard care. More large parallel RCTs are needed including COPD patients, children, and other types, and stages of asthmatic patients.

HOXA9 gene promotor methylation and copy number variation of SOX2 and HV2 genes in cell free DNA: A potential diagnostic panel for non-small cell lung cancer.

BACKGROUND: Most cases of lung cancer are diagnosed at advanced stage. Detection of genetic and epigenetic markers in cell-free DNA (cfDNA) is a promising tool for the diagnosis of lung cancer at an early stage. The aim of this study was to identify non-invasive diagnostic markers in cell free DNA (cfDNA) for non-small cell lung cancer (NSCLC) as it is the most common type of lung cancer. METHODS: We investigated the cfDNA HOXA9 gene promotor methylation by pyrosequencing. Copy number variation of SOX2 and HV2 genes were detected by real-time PCR in cfDNA extracted from plasma samples of 25 newly diagnosed NSCLC patients and 25 age and sex matched controls. RESULTS: Methylation level of HOXA9 was significantly higher in NSCLC patients than controls (p > 0.001). SOX2 showed significantly higher CNV and HV2 showed lower CNV in patients than controls (p > 0.001, p = 0.001 respectively). Receiver Operating Characteristic (ROC) curve analysis for HOXA9 methylation, SOX2 CNV and HV2 CNV showed a discrimination power of 79.4%, 80% and 77.5% respectively and the area under the curve for the combined analysis of the three genes was 0.958 with 88% sensitivity and 100% specificity. CONCLUSIONS: In this study, we suggest a potentially diagnostic panel that may help in detection of lung cancer with high sensitivity and specificity using cell free DNA. This Panel included HOXA9 gene methylation and the CNV of SOX2 and HV2 genes.

Echocardiographic assessment of the right ventricle and its correlation with patient outcome in acute respiratory distress syndrome.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a life-threatening chest disease associated with a poor outcome and increased mortality. It may lead to pulmonary hypertension and, eventually, right ventricular failure. These changes can be investigated by transthoracic echocardiography (TTE) which is considered a non-invasive and cost-effective modality. We studied the role of right ventricular function in the prediction of the severity and mortality in ARDS. MATERIAL AND METHODS: In this observational study, 94 patients suffering from ARDS were subjected to TTE to evaluate the parameters of right ventricular function by measuring tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (RV-FAC), myocardial performance index (Tei index), and systolic pulmonary artery pressure (SPAP) to assess their relation to the severity and mortality in ARDS. RESULTS: TAPSE, SPAP, Tei index, and RV-FAC showed significant differences between survivors and non-survivors after 30 days (all p < 0.001). An increased length of intensive care unit stay was significantly correlated with TAPSE, Tei index, and RV-FAC (p = 0.002' 0.007' and 0.013, respectively). Meanwhile, the length of mechanical ventilation days was significantly correlated with the Tei index only (p < 0.001). Multivariate regression analysis found that TAPSE and the Tei index were independent factors affecting mortality (p = 0.004' and 0.006, respectively). RV-FAC, with a cut-off point ≤ 57%, had the highest sensitivity' while TAPSE, with a cut-off point ≤ 17 mm, had the highest specificity to predict mortality. CONCLUSIONS: Transthoracic echocardiographic parameters of the right ventricle could be used to predict severity and mortality in patients with ARDS with high sensitivity and specificity.