Fetal impact of cystic fibrosis transmembrane conductance regulator modulator use during assisted and natural reproduction and partner pregnancy in men with cystic fibrosis

Background: Increasing availability of highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapy (HEMT) has improved the quality of life and long-term prognosis for many people with CF. Thus, more people with CF are considering parenthood. Almost all menwith CF (MwCF) are infertile because of congenital bilateral absence of the vas deferens (CBAVD). Based on CF animal models, CBAVD occurs early in gestation and is unlikely to be reversible using HEMT, but assisted reproductive techniques (ARTs) can enable MwCF to father children using the sperm in their testes. Animal reproductive models suggest no HEMT teratogenicity, and the amount of exposure of the fetus to HEMT via absorption of seminal fluid through the vaginal wall is predicted to be negligible, although to ensure no sperm exposure to HEMT, the life span of sperm would require MwCF to discontinue CFTR modulators for approximately 3 months before ART. Because abrupt discontinuation of CFTR modulators may result in health decline, MwCF and their providers must consider all potential risks. There are no published data in MwCF regarding use of HEMT during conception and partner pregnancy. Method(s): Beginning in August 2021, CF center staff in the United States, United Kingdom, and Australia completed a two-page anonymous questionnaire regarding MwCF who used CFTR modulators during ART (sperm retrieval and in vitro fertilization) or natural conception with subsequent partner pregnancy. Result(s): Providers have submitted 34 surveys for MwCF on CFTR modulators whose partner became pregnant after use of ART (n = 32) or natural conception (n = 2). The median age of the samplewas 32 (range 24- 43). Fifteen were homozygous for F508del, median percentage predicted forced expiratory volume in 1 second was 76% (range (22-111%), and median body mass index was 24 kg/m2 (range 18.5-32.1). Twenty-three were taking elexacaftor/tezacaftor/ivacaftor. The median time that MwCF were taking CFTR modulators before partner conception was 18 months (range 0-82). One newly diagnosed man initiated HEMT after sperm retrieval. Four MwCF stopped CFTR modulators before sperm retrieval, one of whom experienced pulmonary decline. None of the 19 MwCF whose condom use during pregnancy was known used condoms. Fetal complications in partners of MwCF included three first-trimester miscarriages, two* COVID, two breech presentation, two* vaginal bleeding, and one vasa previa. None of the complications were deemed definitively related to use of CFTR modulators. One MwCF experienced testicular infection after sperm retrieval#. Postpartum complications included three# infants with hypoxemia requiring neonatal intensive care unit stay, three maternal blood loss, one forceps delivery, and one caesarean section. No congenital anomalies were reported for any infant. (*/# overlap). Conclusion(s): Use of CFTR modulator therapy during partner conception and pregnancy in 34 MwCF has not resulted in higher-than-expected miscarriage rates or congenital anomalies. Providers should consider the risk to the health of MwCF combined with the lack of teratogenicity in animal reproductive models and limited safety data in the human fetus before discontinuing CFTR modulators before ART or natural partner conception. Survey collection is ongoing;results will be updated for presentationCopyright © 2022, European Cystic Fibrosis Society. All rights reserved

Chest CT in COVID-19 patients: a clinical need

Purpose: The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has resulted in a global health care crisis. The provision of CT imaging services by radiology departments for COVID-19 patients poses multiple challenges. Thus, the clinical indications and utility of thoracic CT, determined by whether it subsequently alters patient management, in COVID-19 patients is important to establish. Current literature is not well established specifically for the 'Delta' SARS-CoV-2 variant. Methods and Materials: This is a single tertiary hospital centre retrospective review of all consecutive confirmed COVID-19 cases admitted during the peak of the 'Delta' variant wave in Australia who underwent a chest CT. Clinical indication for chest CT and patient management plan pre and post CT were ascertained. Result(s): During this period, 1403 patients were admitted with COVID-19 and 92 patients underwent CT of the thorax, with 18 patients scanned urgently. There were 73 CTPA, 14 CT Chest and 5 HRCT studies. 20 patients were in ICU at the time of scan. Regarding the clinical indications for thoracic CT, 72.8% of studies were to evaluate for pulmonary emboli, 16.2% for assessment of COVID-19 pneumonia complications, 5.4% for tuberculosis and 6.5% for other indications. 21 (23%) of these studies resulted in a change in management with 2 patients having a major change in management (thrombolysis, CT guided aspiration) whilst 19 had minor changes. Of 73 CTPA studies, 11 (15%) patients had evidence of pulmonary embolism. 6 patients underwent a second chest CT for diverse reasons. Conclusion(s): In conclusion, 6% of patients in the cohort of COVID- 19 patients admitted to our centre during the Delta variant wave of COVID-19 in NSW, Australia underwent a CT of the thorax. In 23% of these patients, chest CT resulted in a change in management. 72.8% of chest CT scans were for the evaluation of possible pulmonary emboli. CT was not used for diagnosis or follow-up of COVID-19 in any of our patients.

Longitudinal outcomes of adults and children with cystic fibrosis during the COVID-19 pandemic

Background: The onset of the COVID-19 pandemic was associated with restricted community movement, including limited access to health care facilities, resulting in a change in clinical service delivery to people with cystic fibrosis (CF). The aim of this study was to determine clinical outcomes of Australian adults and children with CF in the 12 months after the onset of the COVID-19 pandemic. Method(s): This longitudinal cohort study used prospectively entered national registry data. Primary outcomes were 12-month change in percentage predicted forced expiratory volume in one second (FEV1pp), body mass index (BMI) in adults, and BMI z-scores in children. A piecewise linear mixed-effects model was used to determine trends in outcomes in the 24 months before and 12 months after the onset of the pandemic. Comparative analysis of hospitalization and service delivery data before and after the onset of the pandemic was conducted. Result(s): Data were available for 3,662 individuals (median age 19.6, range 0-82). Overall registry data completeness was 95%. When trends in outcomes before and after pandemic onset were compared;FEV1pp went from a mean annual change of -0.13% (95% CI, -0.39 to 0.13) to a mean improvement of 1.73% (95% CI, 1.29-2.17). Annual mean annual change in BMI improved from 0.01 kg/m2 (95% CI, -0.07-0.09 kg/m2) to 0.33 kg/m2 (95% CI, 0.23-0.43 kg/m2). Therewas no change in BMI z-scores. Number of hospitalizations decreased from 2,656 to 1,957 ( p < 0.01). Virtual outpatient consultations increased from 8% of toal outpatient consultations before pandemic onset to 47% during the pandemic. Therewas an increase in average number of consultations per patient from a median of 4 (interquartile range 2-5) to 5 (interquartile range 3-6) ( p < 0.01). Conclusion(s): In the 12 months after the onset of the COVID-19 pandemic, improvement was observed in the clinical outcomes of people with CF and the model of care delivery changed from the pre-pandemic period. Health care teams must consider how best to deliver care in light of improved outcomes observed during the COVID-19 pandemic. Acknowledgements: This study was supported by a Health Service Research Grant from the HCF Research Foundation Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Clinical progression of SARS-CoV-2 infection in people with cystic fibrosis: a global observational study

Objectives: As the novel coronavirus (SARS-CoV-2) pandemic continues, people with cystic fibrosis (CF) have been identified as being a vulnerable group. It is essential that people with CF, their families and their clinical teams have the most up-to-date information on the impact of SARS-CoV-2 on their health. This study aims to characterise the impact of SARS-CoV-2 infection in people with CF throughout 2020, identify factors that predict clinical progression of COVID-19, and to describe medium-term follow-up of people who have been infected. Methods: The ‘Cystic Fibrosis Registry Global Harmonization Group’ is a worldwide network of CF Registries that each contributed data on people with CF diagnosed with SARS-CoV-2 infection. In this analysis, we will report on cases contributed from 22 countries diagnosed between 1st February and 13th December 2020. We will present demographic, pre-infection clinical characteristics, symptoms, infection management and outcomes. We will use multivariable logistic regression to assess predictors for hospitalisation with respiratory support and intensive care admission as the outcomes of interest representing clinical progression of COVID-19. Descriptive analysis of medium-term follow-up BMI and FEV1% predicted values will also be undertaken. Results: Results pending. Expected cohort size >1,000, including the 181 previously reported in our paper “The global impact of SARS-CoV-2 in 181 people with cystic fibrosis.” Conclusion: It is expected that the findings of this study will have important implications for shielding advice, clinical care and vaccine prioritisation for people with CF.

In-hospital mortality is associated with inflammatory response in NAFLD patients admitted for COVID-19

Background: Although metabolic risk factors are associated with more severe COVID-19, there is little evidence on outcomes in patients with non-alcoholic fatty liver disease(NAFLD) We here describe the clinical characteristics and outcomes of NAFLD patients in a cohort hospitalised for COVID-19 Methods: This study included all consecutive patients admitted for COVID-19 between February and April 2020 at Imperial College Healthcare NHS Trust, with either imaging of the liver available dated within one year from the admission or a known diagnosis of NAFLD Clinical data and early weaning score(EWS) were recorded NAFLD diagnosis was based on imaging or past medical history andpatients were stratified for Fibrosis-4(FIB-4)index. Clinical endpoints were admission to intensive care unit(ICU)and in-hospital mortality Results: 561 patients were admitted Overall, 193 patients were included in the study Fifty nine patients(30%) died, 9(5%) were still in hospital, and 125(65%) were discharged. The NAFLD cohort(n=61) was significantly younger(60 vs 70 5 years, p=0 046) at presentation compared to the non-NAFLD(n=132) NAFLD diagnosis was not associated with adverse outcomes However,the NAFLD group had higher C reactive protein(CRP) (107 vs 91 2 mg/L,p=0 05) compared to non-NAFLD(n=132) Among NAFLD patients, male gender(p=0 01), ferritin(p=0 003) and EWS(p=0 047) were associated with in-hospital mortality,while the presence of intermediate/high risk FIB-4 or liver cirrhosis was not Conclusion: The presence of NAFLD per se was not associated with worse outcomes in patients hospitalised for COVID-19 Though NAFLD patients were younger on admission,disease stage was not associated with clinical outcomes Yet, mortality was associated with gender and a pronounced inflammatory response in the NAFLD group.