ABSTRACT
Background People with cystic fibrosis (CF) are considered a clinically fragile population with an intrinsic higher risk of developing severe COVID-19, though a certain variability in terms of outcomes and hospitalization has been noticed. Aim To highlight the main risk factors for severe COVID-19 in patients with CF. Methods A systematic review of the current literature was conducted through PubMed and EMBASE databases. English-written articles reporting clinical data on CF subjects with SARS-CoV2 infection were included and analyzed. Selected reports were evaluated for adherence to STROBE recommendations. Results After the selection phase, 9 observational studies were included, 5 of which reported data from CF Registry Global Harmonization Group. The hospitalization rate ranged from 18.2 to 58.1%. The main risk factors for severe outcome were as follows: FEV1 < 70%p, CF-related diabetes, age > 40 years, pancreatic insufficiency, underweight, previous transplant, azithromycin use. Use of dornase alfa was associated with decreased risk for severe disease, while there was insufficient evidence to establish the role of inhaled steroids or CFTR modulators. No solid data regarding specific SARS-CoV-2 therapies in patients with CF emerged. Conclusion Most people with CF experience a mild course of SARS-CoV-2 infection, nevertheless subgroups with higher risk of severe outcome emerged. Maintenance therapies for CF overall did not show a clear preventive effect against severe outcomes, although dornase alfa seems to give some protection. Due to the current lack of data on specific COVID-19 therapies and immunization in patients with CF, further studies are needed to establish their impact in this population.
ABSTRACT
BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) is the newest cystic fibrosis transmembrane conductance regulator (CFTR) modulator drug approved for the treatment of patients with cystic fibrosis (pwCF) aged ≥6 years with at least one copy of the F508del mutation (F) in the CFTR gene or another mutation that is responsive to treatment with ETI. This study determined the effectiveness and safety of ETI in a cohort of severely affected pwCF with an F/F genotype. METHODS: Retrospective observational study in F/F pwCF treated for 48 weeks, enrolled in an ETI managed access program available to subjects with advanced lung disease (ppFEV1 < 40). Twenty-six patients from three centres were included. The main outcomes included lung function, sweat chloride concentration (SCC), nutrition, frequency of pulmonary exacerbations (PEx), CFQ-R, and safety. RESULTS: ppFEV1 improved by 12.06 (95%CI 8.54, 15.57) from baseline after 4 weeks of treatment with ETI, 15.32 (11.3, 19.34) after 24 weeks, and 14.48 (10.64, 18.32) after 48 weeks. The increase in FEV1 was accompanied by a decrease in SCC, improvement of BMI, and noticeable reduction in PEx. An overall good safety profile was observed. CONCLUSIONS: In F/F pwCF with advanced lung disease with an F/F genotype, ETI was safe and associated with clinical improvement.