Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020

Background Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). Methods We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. Results Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/1000 pwCF. Incidence was higher in lung-transplanted patients (n=23) versus non-transplanted patients (n=107) (8.43 versus 2.36 cases/1000). Incidence was higher in pwCF versus the age-matched general population in the age groups <15, 15-24, and 25-49 years (p<0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p=0.133). Conclusions SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination

Protease-antiprotease imbalance in cystic fibrosis

Affects over 8000 patients In the UK. Persistent neutrophilic inflammation is associated with high levels of airway NE. DX-890 is a smallprotein inhibitor ofNE developed by Dyax, USA for use in CF. This project investigated the ex-vivo effects ofDX-890 on human sputum, neutrophils and epithelial cells, to help determine the potential ofDX-890 as a drug for CF. The Ki ofDX-890 was measured to be 11.12 pM. ICso values measured in pure NE and CF sol were similar, demonstrating that DX-890 retained activity in CF sol. Thickened dehydrated CF mucus may prevent access ofDX-890 to NE and reduce efficacy ill vivo. It was hypothesised that, by reducing stickiness of sputum with DNase or surfactant, DX-890 activity would be enhanced. DX-890 inhibited significantly more NE when sputum was pre-treated with surfactant ill vitro. DX-890 reduced release of active NE from fMLP-activated neutrophils and it was found that DX-890 also inhibits NE inside the neutrophil. DX-890 significantly reduced transmigration of neutrophils across a monolayer ofepithelial cells in response to fMLP, implicating NE activity in the process of transmigration. Nasal epithelial cells from CF and non-CF participants were grown in a monolayer and release of the proinflammatory mediator IL-8 was measured. DX-890 prevented NE induced IL-8 release and also IL-8 release induced by CF sol. In conclusion, inhibition ofNE with DX-890 may reduce airway inflammation by minimising production of IL-8 from epithelial cells, and release of active NE from neutrophils. DX-890 efficacy in whole sputum may be enhanced by co-treatment with surfactant. Used in conjunction with current CF therapies such as antibiotics and physiotherapy, DX-890 may help prevent lung damage and prolong life by reducing airwayEThOS - Electronic Theses Online ServiceGBUnited Kingdo

Factors for severe outcomes following SARS-CoV-2 infection in people with cystic fibrosis in Europe

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes. Methods: In this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis. Results: Up to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0-18.4). Median age was 24 years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7-35.5) versus non-lung-transplanted pwCF (16.6; 95% CI: 15.4-17.8) (p≤0.001).SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40 years, at least one F508del mutation and pancreatic insufficiency.Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted versus non-lung-transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function). Conclusion: SARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1 s <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes

Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020

BACKGROUND Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). METHODS We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. RESULTS Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/1000 pwCF. Incidence was higher in lung-transplanted patients (n=23) versus non-transplanted patients (n=107) (8.43 versus 2.36 cases/1000). Incidence was higher in pwCF versus the age-matched general population in the age groups <15, 15-24, and 25-49 years (p<0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p=0.133). CONCLUSIONS SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination

SARS-CoV-2 disrupts clinical research: the role of a rare disease-specific trial network

status: publishe

ECFS CTN 2022 Annual Report

Annual report to CTN sites and CF Patient Organisations of CTN activity and outputs for previous calendar year 202

ECFS CTN 2021 Annual Report

ECFS CTN Annual Report to Sites and Patient Organisation

Isolation, cultivation, and application of primary respiratory epithelial cells obtained by nasal brushing, polyp samples, or lung explants

Here, we present a standardized protocol for isolation, maintenance, and polarization of the respiratory epithelial primary cells from patient samples acquired from nasal brushing, polyp specimens, or lung explants. This protocol generates a clearly defined polarized layer of epithelial cells on filters, with a good number of ciliated cells and a thin layer of mucus. We detail the steps for samples prepared from patients with cystic fibrosis as well as from subjects without cystic fibrosis