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Background Despite high contagiousness and rapid spread, SARS-CoV-2 has led to heterogeneous outcomes across affected nations. Within Europe, the United Kingdom (UK) is the most severely affected country, with a death toll in excess of 100.000 as of January 2021. We aimed to compare the national impact of COVID-19 on the risk of death in UK cancer patients versus those in continental Europe (EU). Methods We performed a retrospective analysis of the OnCovid study database, a European registry of cancer patients consecutively diagnosed with COVID-19 in 27 centres from February 27 to September 10, 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline, including oncological and COVID-19 specific therapy across UK and EU cohorts and evaluated the association of these factors with the risk adverse outcome in multivariable Cox regression models. Findings Compared to EU (n=924), UK patients (n=468) were characterised by higher case fatality rates (40.38% versus 26.5%, p<0.0001), higher risk of death at 30 days (hazard ratio, HR 1.64 [95%CI 1.36-1.99]) and 6 months after COVID-19 diagnosis (47.64% versus 33.33%, p<0.0001, HR 1.59 [95%CI 1.33-1.88]). UK patients were more often males, of older age and more co-morbid than EU counterparts (p<0.01). Receipt of anticancer therapy was lower in UK versus EU patients (p<0.001). Despite equal proportions of complicated COVID-19, rates of intensive care admission and use of mechanical ventilation, UK cancer patients were less likely to receive anti-COVID-19 therapies including corticosteroids, anti-virals and interleukin-6 antagonists (p<0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of patient’s age, gender, tumour stage and status, number of co-morbidities, COVID-19 severity, receipt of anticancer and anti-COVID-19 therapy. Rates of permanent cessation of anticancer therapy post COVID-19 were similar in UK versus EU. Interpretation UK cancer patients have been more severely impacted by the unfolding of the COVID-19 pandemic despite societal risk mitigation factors and rapid deferral of anticancer therapy. The increased frailty of UK cancer patients highlights high-risk groups that should be prioritised for anti-SARS-CoV-2 vaccination. Continued evaluation of long-term outcomes is warranted.

IMPORTANCEWhether the severity and mortality of COVID-19 in patients with cancer have improved in terms of disease management and capacity is yet to be defined. OBJECTIVE To test whether severity and mortality from COVID-19 among patients with cancer have improved during the course of the pandemic. DESIGN, SETTING, AND PARTICIPANTSOnCovid is a European registry that collects data on consecutive patients with solid or hematologic cancer and COVID-19. This multicenter case series study included real-world data from 35 institutions across 6 countries (UK, Italy, Spain, France, Belgium, and Germany). This update included patients diagnosed between February 27, 2020, and February, 14, 2021. Inclusion criteria were confirmed diagnosis of SARS-CoV-2 infection and a history of solid or hematologic cancer.EXPOSURES SARS-CoV-2 infection.MAIN OUTCOMES AND MEASURES Deaths were differentiated at 14 days and 3 months as the 2 landmark end points. Patient characteristics and outcomes were compared by stratifying patients across 5 phases (

Background: Aging cystic fibrosis (CF) patients are at high risk of developing CF-related diabetes (CFRD). Decrease in insulin secretion over time is the main hypothesis to explain this increasing prevalence but mechanisms are still not well elucidated. The objective is to assess evolution of glucose tolerance and insulin secretion/sensitivity in aging CF patients. Methods: This is a retro-prospective observational analysis in the older adult CF patients from the Montreal Cystic Fibrosis Cohort (n = 46; at least 35 years old at follow-up) and followed for at least 4 years. Baseline and followup (last visit to date) 2-h oral glucose tolerance test (OGTT with glucose and insulin measurements every 30 min) were performed. Pulmonary function test (FEV 1 ) and anthropometric data were measured the same day. Insulin sensitivity was measured by the Stumvoll index. Results: After a mean follow-up of 9.9 ± 2.6 years, mean age at follow-up was 43.5 ± 8.1 years old. An increase of body weight (+2.6 ± 6.5 kg, p = 0.01) and a decrease in pulmonary function (FEV 1 ; 73.4 ± 21.2% to 64.5 ± 22.4%, p ≤ 0.001) were observed. Overall, insulin secretion is maintained at follow-up but all OGTT glucose values increased (for all values, p ≤ 0.028). At follow-up, 28.3% of patients had a normal glucose tolerance while 71.7% had abnormal glucose tolerance (AGT). AGT patients decreased their insulin sensitivity over time (p = 0.029) while it remained the same in NGT patients (p = 0.917). Conclusion:In older CF patients, the progression of impaired glucose tolerance is occurring with stable insulin secretion but reduced insulin sensitivity.

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Bamlivimab + etesevimab therapy induces SARS-COV-2 immune escape mutations and secondary clinical deterioration in Covid-19 patients with B cell malignancies F.

Aims/hypothesis Cystic fibrosis-related diabetes (CFRD) affects up to 50% of adults with cystic fibrosis (CF) and its presence is associated with adverse effects on nutritional status and pulmonary function. Early diagnosis could minimise CFRD morbidity, yet current methods of an OGTT at 0 and 2 h yield unreliable results. Our aim was to determine which indices from a 2 h OGTT with sampling every 30 min might improve prediction of CFRD. Methods Cross-sectional analysis at baseline (n = 293) and observational prospective analysis (n = 185; mean follow-up of 7.5 ± 4.2 years) of the Montreal Cystic Fibrosis Cohort were performed. Blood glucose and insulinaemia OGTT variables were studied in relation to lung function (forced expiratory volume in 1 s [FEV1]), BMI and risk of developing CFRD. Results At baseline, maximum OGTT glucose (G max ) was negatively associated with FEV1 (p = 0.003). Other OGTT values, including classical 2 h glucose, were not. A higher G max was associated with lower insulin secretory capacity, delayed insulin peak timing and greater pancreatic insufficiency (p < 0.01). G max was positively associated with the risk of developing CFRD (p = 0.0029); no individual with a G max < 8 mmol/l developed CFRD over the following decade. No OGTT variable correlated to the rate of change in BMI or FEV1. Conclusions/interpretation In adults with CF, G max is strongly associated with the risk of developing CFRD; G max < 8 mmol/l could identify those at very low risk of future CFRD. G max is higher in individuals with pancreatic insufficiency and is associated with poorer insulin secretory capacity and pulmonary function. KeywordsAdult . Blood glucose variables . Cystic fibrosis . Lung function . Oral glucose tolerance test Abbreviations AUC INS/GLU I AUC /G AUC CF Cystic fibrosis CFRD Cystic fibrosis-related diabetes CFTR CF transmembrane conductance regulator FEV1 Forced expiratory volume in 1 s G AUC Total AUC for glucose G max Peak OGTT glucose I AUC Total AUC for insulin IGT Impaired glucose tolerance I max Peak OGTT insulin ISI Insulin sensitivity index MCFC Montreal Cystic Fibrosis Cohort NGT Normal glucose tolerance * Rémi Rabasa-Lhoret

Aim Cystic fibrosis (CF) patients are at high risk of developing CF-related diabetes (CFRD). In non-CF patients, liver disease, specifically steatosis and non-alcoholic fatty liver disease (NAFLD), is strongly associated with type 2 diabetes. We compared glycemic status and metabolic profiles in CF patients according to a biomarker of hepatic injury, alanine aminotransferase (ALT). Methods We conducted a cross-sectional study among 273 adult CF patients recruited from the Montreal CF Cohort. A 2-hour oral glucose tolerance test (OGTT) was performed to collect glucose and insulin measures every 30 minutes. Fasting ALT levels and anthropometric measures were also obtained. Patients were categorized into 2 groups based on ALT cut-off of 25 U/L. Results Patients in the high ALT group were mostly men (83%), had higher mean weight and BMI (p<0.001) and showed elevated glucose levels throughout OGTT (p≤0.01). When stratified by sex, only men with high ALT showed significantly higher weight (p<0.001), higher glycemic values at 60, 90 and 120 minutes of OGTT (p≤0.01), higher frequency of de novo CFRD (20.5% vs 8.2%, p = 0.04) as well as lower insulin sensitivity than men with normal ALT (p = 0.03). ALT levels were strongly associated with HOMA-IR in CFRD patients (p = 0.001, r 2 = 0.28). Conclusions Adult CF men with higher ALT show an increased frequency of dysglycemia and de novo CFRD, lower insulin sensitivity and higher eight. Our data suggests that ALT levels could be an interesting tool to guide targeted diabetes screening, particularly among CF men. Prospective studies are needed to confirm these observations.