Factors Associated With Clinical Progression to Severe COVID-19 in People With Cystic Fibrosis: A Global Observational Study

Background: This international study aimed to characterise the impact of acute SARS-CoV-2 infection in people with cystic fibrosis and investigate factors associated with severe outcomes.Methods: Data from 22 countries prior to 13th December 2020 and the introduction of vaccines were included. It was de-identified and included patient demographics, clinical characteristics, treatments, outcomes and sequelae following SARS-CoV-2 infection. Multivariable logistic regression was used to investigate factors associated with clinical progression to severe COVID-19, using the primary outcome of hospitalisation with supplemental oxygen.Findings: SARS-CoV-2 was reported in 1555 people with CF, 1452 were included in the analysis. One third were aged <18 years, and 9.4% were solid-organ transplant recipients. 74.5% were symptomatic and 22% were admitted to hospital. Transplanted patients were hospitalised with supplemental oxygen therapy (21.9%) more often than non-transplanted (8.8%) and being transplanted was independently associated with the primary outcome (adjusted OR 2.45 95%CI 1.27-4.71 p=0.007). In the non-transplanted cohort, 39.5% of patients with ppFEV170%: a 17-fold increase in odds. Worse outcomes were independently associated with older age, non-white race, being underweight, and CF-related diabetes. Prescription of highly effective CFTR modulator therapies was associated with a significantly reduced odds of being hospitalised with oxygen (AOR 0.43 95%CI 0.31-0.60 p<0.001).Interpretation: This is the first study to show that there is a protective effect from the use of CFTR modulator therapy and that people with CF from an ethnic minority are at more risk of severe infection with SARS-CoV-2.Funding Information: AS, RC, have funding from Canadian Institutes of Health Research to support the Global Registry Collaboration on Covid and CF.Declaration of Interests: All authors declare no conflicts of interest in relationship to this work. Outside of this work the following authors declare payments or honoraria to them or their institution for a combination of lectures, presentations, educational events, advisory boards, steering groups, grants or consultancy fees: SC-Vertex, Chiesi, Profile, Zambon. RC- Vertex, P-RB – Astra-Zeneca, Boehringer Ingelheim, GSK, Insmed, Chiesi, Pfizer, Vertex, Zambon. I deM – Vertex,LN – Vertex, Boehringer,LVS-F – Vertex, AS – Vertex.Ethics Approval Statement: De-identified data were collected according to each individual nation’s CF registry ethics approval or national guidelines.