Genetic and non-genetic factors affecting the expression of COVID-19 relevant genes in the large airway epithelium

Introductory paragraphParticular host and environmental factors influence susceptibility to severe COVID-19. We analyzed RNA-sequencing data from bronchial epithelial brushings - a relevant tissue for SARS-CoV-2 infection - obtained from three cohorts of uninfected individuals, and investigated how non-genetic and genetic factors affect the regulation of host genes implicated in COVID-19. We found that ACE2 expression was higher in relation to active smoking, obesity, and hypertension that are known risk factors of COVID-19 severity, while an association with interferon-related inflammation was driven by the truncated, non-binding ACE2 isoform. We discovered that expression patterns of a suppressed airway immune response to early SARS-CoV-2 infection, compared to other viruses, are similar to patterns associated with obesity, hypertension, and cardiovascular disease, which may thus contribute to a COVID-19-susceptible airway environment. eQTL mapping identified regulatory variants for genes implicated in COVID-19, some of which had pheWAS evidence for their potential role in respiratory infections. These data provide evidence that clinically relevant variation in the expression of COVID-19-related genes is associated with host factors, environmental exposures, and likely host genetic variation.

Impaired Global Right Ventricular Longitudinal Strain Predicts Long-Term Adverse Outcomes in Patients with Pulmonary Arterial Hypertension

BACKGROUND: New 2-dimensional strain echocardiography enables quantification of right ventricular (RV) mechanics by assessing global longitudinal strain of RV (GLSRV) in patients with pulmonary arterial hypertension (PAH). However, the prognostic significance of impaired GLSRV is unclear in these patients. METHODS: Comprehensive echocardiography was performed in 51 consecutive PAH patients without atrial fibrillation (40 females, 48 +/- 14 years old) with long-term follow-up. GLSRV was measured with off-line with velocity vector imaging (VVI, Siemens Medical System, Mountain View, CA, USA). RESULTS: GLSRV showed significant correlation with RV fractional area change (r = -0.606, p or = -15.5%) was associated with lower event-free survival (HR = 4.906, p = 0.001) and increased mortality (HR = 8.842, p = 0.005). CONCLUSION: GLSRV by VVI showed significant correlations with conventional echocardiographic parameters indicating RV systolic function. Lower GLSRV (> or = -15.5%) was significantly associated with presence of adverse clinical events and deaths in PAH patients.

Relationship between Right Ventricular Longitudinal Strain, Invasive Hemodynamics, and Functional Assessment in Pulmonary Arterial Hypertension

BACKGROUND AND OBJECTIVES: Right ventricular longitudinal strain (RVLS) is a new parameter of RV function. We evaluated the relationship of RVLS by speckle-tracking echocardiography with functional and invasive parameters in pulmonary arterial hypertension (PAH) patients. SUBJECTS AND METHODS: Thirty four patients with World Health Organization group 1 PAH (29 females, mean age 45+/-13 years old). RVLS were analyzed with velocity vector imaging. RESULTS: Patients with advanced symptoms {New York Heart Association (NYHA) functional class III/IV} had impaired RVLS in global RV (RVLS(global), -17+/-5 vs. -12+/-3%, p<0.01) and RV free wall (RVLS(FW), -19+/-5 vs. -14+/-4%, p<0.01 to NYHA class I/II). Baseline RVLS(global) and RVLS(FW) showed significant correlation with 6-minute walking distance (r=-0.54 and r=-0.57, p<0.01 respectively) and logarithmic transformation of brain natriuretic peptide concentration (r=0.65 and r=0.65, p<0.01, respectively). These revealed significant correlations with cardiac index (r=-0.50 and r=-0.47, p<0.01, respectively) and pulmonary vascular resistance (PVR, r=0.45 and r=0.45, p=0.01, respectively). During a median follow-up of 33 months, 25 patients (74%) had follow-up examinations. Mean pulmonary arterial pressure (mPAP, 54+/-13 to 46+/-16 mmHg, p=0.03) and PVR (11+/-5 to 6+/-2 wood units, p<0.01) were significantly decreased with pulmonary vasodilator treatment. RVLS(global) (-12+/-5 to -16+/-5%, p<0.01) and RVLS(FW) (-14+/-5 to -18+/-5%, p<0.01) were significantly improved. The decrease of mPAP was significantly correlated with improvement of RVLS(global) (r=0.45, p<0.01) and RVLS(FW) (r=0.43, p<0.01). The PVR change demonstrated significant correlation with improvement of RVLS(global) (r=0.40, p<0.01). CONCLUSION: RVLS correlates with functional and invasive hemodynamic parameters in PAH patients. Decrease of mPAP and PVR as a result of treatment was associated with improvement of RVLS.