RSV infection is characterized by airway edema. Stabilization of hypoxia inducible factor-1alpha (HIF-1alpha) is important in both inflammation and edema formation. In this study we evaluated whether RSV induced release of nitric oxide (NO) by bronchial airway epithelial cells leading to the stabilization of HIF-1alpha and subsequent transcription of VEGF(165). Primary human bronchial epithelial cells (HBEpC) were used; cell supernatants were analyzed. Western blot analysis was used for the detection of HIF-1alpha. Bronchial airway epithelial monolayer permeability was assessed using electric cell-substrate impedance sensing (ECIS) in real time. There was increased stabilization of HIF-1alpha in RSV infected cells. Addition of an NO inhibitor blocked RSV mediated HIF-1alpha expression. Antagonism of NO also inhibited VEGF production and HBEpC monolayer permeability. Our results demonstrate that in HBEpC, RSV induced NO causes stabilization of HIF-1alpha in vitro.
Background The number of COVID-19 infected patients has been soaring in the Middle East countries. The disease poses a significant threat, decisions about prioritizing care should be made in accordance with the proven risk factors for complications. Objective The present study provides the first bespoke prediction model in the Middle East to identify COVID-19 patients, who are at higher risk for complications. Method A case-control study design was adopted to compare the characteristics of successfully recovered patients with those who had complications. Complications were defined as admission to the intensive care unit, mechanical ventilation, sepsis or septic shock, pneumonia or respiratory failure, and death. The prediction model was created through multivariable logistic regression. C statistic was used to assess overall discriminatory ability. Results All COVID-19 infected hospitalized patients (n = 133) in Amman – Jordan were included in the study. Successfully recovered were 125 patients. The median age (IRQ) was 26 (10-40). Almost 30% were >40 years. Patients with complications were eight patients, age 63 (51.5-71.5). The prediction model identified the following variables as risk factors: diabetes (OR = 59.7; 95% CI: 3.5–1011.5, P = 0.005), fever (OR = 24.8; 95% CI: 1.4–447.3, P = 0.029), SHORTNESS OF BREATH (OR = 15.9; 95% CI: 1.3–189.7, P = 0.029), body mass index (OR = 0.74; 95% CI: 0.61–0.88, P = 0.001), abnormal Neutrophils (OR = 16.8; 95% CI: 1.0–292.0, P = 0.053). Prediction model was statistically significant, χ2(5) = 86.1, p < 0.0005. Conclusions Unlike reports from China, the most influential variables that led to disease progression in Jordanian patients were diabetes, fever, shortness of breath, body mass index, and abnormal neutrophils. Similar to reports from the USA, smoking was not a leading factor for complications. Comorbidities and patient health status, rather than age, were the primary risk factors for complications. Treatment with Hydroxychloroquine showed no protective effect.
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