RECOVER - the Real World Clinical Outcomes with Novel Modulator therapy combinations in people with cystic fibrosis

Background: Real-world, post-approval studies contribute significantly to the evidence surrounding the impact of new treatments, including CFTR modulators, but can be complex undertakings. Elexacaftor-tezacaftor-ivacaftor (ETI) was approved by EMA sooner than expected in August 2020 during a global pandemic. Method: RECOVER, a multi-centre, post-approval study examining the impact of ETI, and conducted in 8 clinical sites in Ireland and the UK over 2 years, examines important outcomes in children and adults prescribed ETI. The study will be conducted in 2 phases in line with ETI approval: 12+ and 6–11. In addition to routine data collected as part of normal care, key RECOVER endpoints include lung clearance index (LCI), spirometry-controlled CT, treatment adherence, GI symptoms, inflammation, liver disease markers, nasal inflammation and nitric oxide metabolism. Results: To date, 96 participants (56% female) out of a target of 137 in people with CFaged 12 and above, have been recruited (predominantly 12–18yrs to date). Recruitment and sample collection has been impacted by the effect of COVID-19 on CF care and CF centre attendance. Key challenges have included: Sputum collection (risks of induction and non-sputum producing participants) and coordination of study activities with limited clinic attendance. Despite this, key baseline data, prior to commencing treatment, has been successfully collected on the majority of participants to date. For subjects recruited to date, 56% have F508del/F508del and 44% F508del/minimum function mutations, mean age is 16.1 years, mean FEV1 83.6% (23–111%), mean LCI 12.2 (6.9–24.3). Recruitment and data collection is ongoing. Conclusion: Despite the impact of accelerated approval and COVID-19, we have been able to proceed with study initiation, recruitment and sample collection. Data from RECOVER and other international post-approval studies is likely to add significantly to our understanding of the impact of ETI on people with CF.

Low prevalence of SARS-CoV-2 detected in symptomatic children admitted to hospital

Aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China in 2019 and is responsible for the condition known as COVID-19. COVID-19 was first reported in Ireland in February 2020 with University Hospital Limerick’s (UHL) first paediatric case reported on 4th March 2020. Studies have shown clinical manifestations of children’s cases are generally less severe than those of adults. UHL serves a catchment population of approximately 100,000 children. We aimed to describe the clinical presentation, and prevalence of SARS-CoV-2, in children requiring inpatient hospitalization during the initial phase of the pandemic in Ireland. Methods Data were examined relating to all inpatients aged 0 – 16 years admitted with a queried or confirmed diagnosis of COVID-19 from 8th February 2020 to 8th June 2020. Emergency Department notes and inpatient records along with laboratory and radiology records were reviewed. Results 220 paediatric inpatients were tested by PCR for SARS-CoV-2 during this period;101 (45.9%) were female. Ninety-five (43.2%) were diagnosed with ‘viral illnesses’. Seven (3.2%) had laboratory-confirmed SARS-CoV-2, with an average age of 8.1 years (range: 0.59 years to 13.77 years). There were two Kawasaki-like illnesses admitted;both tested negative for SARS-CoV-2 on PCR. In our SARS-CoV-2 positive cohort, there was no associated significant morbidity and no associated mortality. Conclusion During the initial phase of the COVID-19 pandemic, prevalence of confirmed SARS-CoV-2 in symptomatic hospitalised children was low at 3.2%.