Are MUC5B and TERT mutations genetic risk factors for pulmonary fibrosis in individuals with severe COVID-19?

Introduction: The genetic risk factors for Coronavirus disease-2019 (COVID19)-associated pulmonary fibrosis (CAPF) are not clearly defined. Mutations in the genes encoding telomerase reverse transcriptase (TERT) and mucin 5B (MUC5B) are well-known genetic risk factors for pulmonary fibrosis. In this study, we aimed to show whether the most common proven mutations of pulmonary fibrosis affect the development of CAPF. Materials and Methods: Forty-eight patients who were matched for age, gender, COVID-19 disease severity, and respiratory support type and needed high flow nasal cannula, non-invasive mechanical ventilator, or invasive mechanical ventilator due to COVID-19 were followed up prospectively. Eighteen patients were excluded from the follow-up due to known structural lung disease, collagen tissue disease, and occupational exposure to fibrosis. The patients were called for follow-up three months after discharge, and CT was performed. Those with fibrosis (n= 15) in the third-month follow-up CT were included in the CAPF group, and those with complete resolution (n= 15) were included in the control group. Blood samples were taken for genetic analysis. Result: TERT gene study revealed that six (40%) of the fibrosis group was normal, while five were heterozygous (33.3%). MUC5B polymorphism was not detected in 10 (66.7%) of the fibrosis group. Conclusions: Individuals with TERT mutations may be at a higher risk for CAPF. Further studies are needed to clarify the genetic risk factors for CAPF.

Assessment of aortic elastic properties in patients with sarcoidosis.

BACKGROUND: Sarcoidosis is an inflammatory granulomatous disease of unknown etiology that involves multiple organ systems. Many studies have shown a strong relationship between inflammation and atherosclerosis. The aim of this study is to investigate the relationship between elastic properties of the aorta and the duration of the disease in patients with sarcoidosis. METHOD: The study population included 52 patients with sarcoidosis (22 men, mean age = 42.7 ± 10.7 years, and mean disease duration = 38.8 ± 10.8 months) and 50 healthy control subjects (18 men, and mean age = 42.0 ± 8.0 years). Aortic stiffness (ß) index, aortic strain (AoS) and aortic distensibility (AoD) were calculated from the aortic diameters measured by transthoracic echocardiography and blood pressure obtained by sphygmomanometer. Cardiac functions were determined by using routine echocardiographic evaluation consist of standard two-dimensional and conventional Doppler and tissue Doppler imaging. RESULTS: The conventional echocardiographic parameters were similar between patients and controls. There were significant differences between the control and the patient groups in ß index (1.63 ± 0.55 vs 2.44 ± 1.54, p = 0.001), AoS (15.61 ± 5.69 vs 10.93 ± 4.11%, p < 0.001) and AoD (6.35 ± 2.64 vs 4.66 ± 1.98, 10 (-6) cm(2)/dyn, p = 0.001). There were statistically significant negative correlations between the disease duration and AoD (r = -0.46, p = 0.01) and AoS (r= -0.44, p = 0.002), whereas there was a positive correlation between the disease duration and ß index (r = 0.37, p = 0.01). In multivariate analysis, disease duration was significantly related with AoD, AoS and ß index (respectively, RR = 3.28, p = 0.002; RR = 3.03, p = 0.004; RR = 2.39, p = 0.02). CONCLUSION: We observed that elastic properties of the aorta alter in patients with sarcoidosis. We also have demonstrated a statistically significant correlation between aortic elastic properties and the disease duration.

Assessment of atrial conduction time in patients with sarcoidosis.

OBJECTIVES: Sarcoidosis is an inflammatory granulomatous disease of unknown cause that involves multiple organ systems. Myocardial involvement is usually associated with poor prognosis, but diagnosis of cardiac sarcoidosis is frequently difficult. The aim of this study was to investigate the atrial conduction time in patients with sarcoidosis by using high-usefulness tissue Doppler echocardiography. METHODS: The study population included 49 patients with sarcoidosis (19 men; mean age, 40.5 ± 9.8 years; mean disease duration, 35.7 ± 15.3 months) and 45 healthy control subjects (17 men; mean age, 40.7 ± 7.2 years). From the 12-lead electrocardiogram, P wave dispersion (PWD) was calculated. The timing of atrial contractions (PA) was measured as the intervals between the onset of P wave on electrocardiogram and the beginning of A-wave on TDI, and atrial electromechanical delay (EMD) was calculated from the lateral (PA lateral) and septal (PA septal) mitral annulus and lateral tricuspid annulus (PA tricuspid). RESULTS: Both PA lateral and PA septal were significantly longer in patients with sarcoidosis than control subjects (67.9 ± 16.1 vs 56.3 ± 13.1, P < 0.001; and 54.8 ± 15.2 vs 45.1 ± 14.2 ms, P = 0.002, respectively). Intra-atrial (PA septal-PA tricuspid) and interatrial (PA lateral-PA tricuspid) EMD were significantly higher in sarcoidosis groups (12.6 ± 7.5 vs 8.0 ± 7.1, P = 0.003; and 25.7 ± 9.8 vs 19.3 ± 7.7 ms, P = 0.001, respectively). Similarly, maximum P-wave duration and PWD were significantly longer in patients with sarcoidosis than control subjects (105.2 ± 11.8 vs 96.7 ± 15.4, P = 0.004 and 24.7 ± 5.6 vs 19.7 ± 7.1 ms, P = 0.001, respectively). There were significant positive correlations between the disease duration and interatrial EMD (r = 0.56, P < 0.001) and intra-atrial EMD (r = 0.66, P < 0.001). Positive correlation also was present between the disease duration and PWD (r = .62, P < 0.001). CONCLUSIONS: Atrial EMD was found prolonged in patients with sarcoidosis. We also have demonstrated that PWD, interatrial and intra-atrial EMD were significantly correlated with disease duration. This study calls attention to measurement of atrial conduction time that may be clinically helpful in the recognition of cardiac involvement.