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.

BackgroundSARS-Co-V-2 infection in people with CF (pwCF) can lead to severe outcomes.MethodsIn 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.ResultsUp to 31 December 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% were admitted to hospital, 2.5% to intensive care. Regretfully 11 pwCF (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2–6-fold more frequent in lung-transplanted versus non-lung transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, CF-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function).ConclusionSARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in one second (FEV1) <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes.

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Cystic fibrosis (CF) is a monogenic disease due to mutations in the CFTR gene. Yet, variability in CF disease presentation is presumed to be affected by modifier genes, such as those recently demonstrated for the pulmonary aspect. Here, we conduct a modifier gene study for meconium ileus (MI), an intestinal obstruction that occurs in 16–20% of CF newborns, providing linkage and association results from large family and case–control samples. Linkage analysis of modifier traits is different than linkage analysis of primary traits on which a sample was ascertained. Here, we articulate a source of confounding unique to modifier gene studies and provide an example of how one might overcome the confounding in the context of linkage studies. Our linkage analysis provided evidence of a MI locus on chromosome 12p13.3, which was segregating in up to 80% of MI families with at least one affected offspring (HLOD = 2.9). Fine mapping of the 12p13.3 region in a large case–control sample of pancreatic insufficient Canadian CF patients with and without MI pointed to the involvement of ADIPOR2 in MI (p = 0.002). This marker was substantially out of Hardy–Weinberg equilibrium in the cases only, and provided evidence of a cohort effect. The association with rs9300298 in the ADIPOR2 gene at the 12p13.3 locus was replicated in an independent sample of CF families. A protective locus, using the phenotype of no-MI, mapped to 4q13.3 (HLOD = 3.19), with substantial heterogeneity. A candidate gene in the region, SLC4A4, provided preliminary evidence of association (p = 0.002), warranting further follow-up studies. Our linkage approach was used to direct our fine-mapping studies, which uncovered two potential modifier genes worthy of follow-up.

Twenty-nine children with cystic fibrosis (CF) were investigated for quinolone-induced arthropathy. Magnetic resonance imaging (MRI) was performed in 14/14 children treated with ofloxacin or ciprofloxacin and in 10/15 of those never treated with quinolones. The frequency of pathologic MRI findings, concerning cartilage thickness, careful analysis of the cartilage structure, presence of edema, cartilage-bone borderline and the presence of fluid in joints did not show any difference between both groups. Thus the presence of quinolone-induced arthrotoxicity cannot be confirmed in this study.