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 sequalae 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. RESULTS: 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. In the non-transplanted cohort, 39.5% of patients with ppFEV1<40% were hospitalised with oxygen verses 3.2% with ppFEV >70%: a 17-fold increase in odds. Worse outcomes were independently associated with older age, non-white race, underweight body mass index, 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). Transplanted patients were hospitalised with supplemental oxygen therapy (21.9%) more often than non-transplanted (8.8%) and was independently associated with the primary outcome (Adjusted OR 2.45 95%CI 1.27-4.71 p=0.007). CONCLUSIONS: 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.

Baseline Cystic fibrosis disease severity has an adverse impact on pregnancy and infant outcomes, but does not impact disease progression.

BACKGROUND: With increasing longevity and quality of life in adults with Cystic fibrosis (CF), growing maternity rates are reported. Women with severe CF are becoming pregnant, with unpredictable maternal and fetal outcomes. AIM: To determine how baseline disease severity, pancreatic insufficiency (PI) and Pseudomonas aeruginosa (PA) infection affect fertility, the pregnancy course, delivery, neonatal outcome, and subsequent disease progression. METHODS: A multicenter-retrospective cohort study. Data on patients that had been pregnant between 1986-2018 was collected from ten CF centers worldwide. Disease severity [mild or moderate-severe (mod-sev)] was defined according to forced expiratory volume % predicted in 1 second (FEV1) and body mass index (BMI). Three time periods were compared, 12 months prior to conception, the pregnancy itself and the 12 months thereafter. RESULTS: Data was available on 171 pregnancies in 128 patients aged 18-45 years; 55.1% with mod-sev disease, 43.1% with PI and 40.3% with PA. Women with mod-sev disease had more CF-related complications during and after pregnancy and delivered more preterm newborns. However, FEV1 and BMI decline were no different between the mild and mod-sev groups. A more rapid decline in FEV1 was observed during pregnancy in PI and PA infected patients, though stabilizing thereafter. PI was associated with increased risk for small for gestational age infants. CONCLUSION: Baseline disease severity, PA infection and PI have an adverse impact on infant outcomes, but do not impact significantly on disease progression during and after pregnancy. Consequently, pregnancies in severe CF patients can have a good prognosis.

Clinical characteristics of SARS-CoV-2 infection in children with cystic fibrosis: An international observational study.

BACKGROUND: The presence of co-morbidities, including underlying respiratory problems, has been identified as a risk factor for severe COVID-19 disease. Information on the clinical course of SARS-CoV-2 infection in children with cystic fibrosis (CF) is limited, yet vital to provide accurate advice for children with CF, their families, caregivers and clinical teams. METHODS: Cases of SARS-CoV-2 infection in children with CF aged less than 18 years were collated by the CF Registry Global Harmonization Group across 13 countries between 1 February and 7 August 2020. RESULTS: Data on 105 children were collated and analysed. Median age of cases was ten years (interquartile range 6-15), 54% were male and median percentage predicted forced expiratory volume in one second was 94% (interquartile range 79-104). The majority (71%) of children were managed in the community during their COVID-19 illness. Out of 24 children admitted to hospital, six required supplementary oxygen and two non-invasive ventilation. Around half were prescribed antibiotics, five children received antiviral treatments, four azithromycin and one additional corticosteroids. Children that were hospitalised had lower lung function and reduced body mass index Z-scores. One child died six weeks after testing positive for SARS-CoV-2 following a deterioration that was not attributed to COVID-19 disease. CONCLUSIONS: SARS-CoV-2 infection in children with CF is usually associated with a mild illness in those who do not have pre-existing severe lung disease.

The global impact of SARS-CoV-2 in 181 people with cystic fibrosis.

With the growing SARS-CoV-2 pandemic, we need to better understand its impact in specific patient groups like those with Cystic Fibrosis (CF). We report on 181 people with CF (32 post-transplant) from 19 countries diagnosed with SARS-CoV-2 prior to 13 June 2020. Infection with SARS-CoV-2 appears to exhibit a similar spectrum of outcomes to that seen in the general population, with 11 people admitted to intensive care (7 post-transplant), and 7 deaths (3 post-transplant). A more severe clinical course may be associated with older age, CF-related diabetes, lower lung function in the year prior to infection, and having received an organ transplant. Whilst outcomes in this large cohort are better than initially feared overall, possibly due to a protective effect of the relatively younger age of the CF population compared to other chronic conditions, SARS-CoV-2 is not a benign disease for all people in this patient group.

Isolation and first draft genome sequence of a linezolid-dependent Staphylococcus aureus clinical strain.

Background: Antibiotic-dependent pathogenic bacteria are sporadically isolated from patients that received prolonged antibiotic treatments. Evolution of antibiotics dependence and its clinical implications are scarcely studied. Materials & methods: A linezolid-dependent Staphylococcus aureus strain was isolated from a cystic fibrosis patient. A draft genome sequence was obtained and searched for known antibiotics resistance determinants and virulence factors. Results: The genome was assembled into 79 contigs for a total of 2.83 Mbp. This strain is a sequence type 5 methicillin-resistant Staphylococcus aureus with a type I SCCmec cassette also conserving the Panton-Valentine leukocidin. The G2576T substitution, conferring linezolid resistance, was harbored by all five copies of the 23S rRNA. Conclusion: The linezolid-dependent strain is related to a strain circulating in Latin America that acquired a mutation conferring linezolid resistance.

[Secondary acute myeloid leukemia in a lung allograft recipient. Report of one case]. / Leucemia mieloide aguda secundaria a inmunosupresores en una paciente trasplantada de pulmón, una inusual y letal entidad.

Secondary acute myeloid leukemia is a very rare complication in patients with solid organ transplantation. We report a 62 years old female who received a right single lung allograft for idiopathic pulmonary fibrosis. Her immunosuppression scheme consisted in prednisone, azathioprine, and tacrolimus. Two years after the transplantation, she presented with progressive pancytopenia. Bone marrow aspiration was informed as a M4 acute myeloid leukemia, confirmed by flow cytometry. Cytogenetic study was complex, including alterations in chromosome 5. A secondary acute myeloid leukemia was diagnosed. The patient developed nosocomial pneumonia and died a few days after the diagnosis, without specific treatment. The pathogenesis of acute myeloid leukemia is probably related to the intensive exposure to immunosuppressant, especially azathioprine, in these patients.

Leucemia mieloide aguda secundaria a inmunosupresores en una paciente trasplantada de pulmón, una inusual y letal entidad / Secondary acute myeloid leukemia in a lung allograft recipient. Report of one case

Secondary acute myeloid leukemia is a very rare complication in patients with solid organ transplantation. We report a 62 years old female who received a right single lung allograft for idiopathic pulmonary fibrosis. Her immunosuppression scheme consisted in prednisone, azathioprine, and tacrolimus. Two years after the transplantation, she presented with progressive pancytopenia. Bone marrow aspiration was informed as a M4 acute myeloid leukemia, confirmed by flow cytometry. Cytogenetic study was complex, including alterations in chromosome 5. A secondary acute myeloid leukemia was diagnosed. The patient developed nosocomial pneumonia and died a few days after the diagnosis, without specific treatment. The pathogenesis of acute myeloid leukemia is probably related to the intensive exposure to immunosuppressant, especially azathioprine, in these patients.