Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients

SixTrack Version 5: Status and new developments

SixTrack Version 5 is a major SixTrack release that introduces new features, with improved integration of the existing ones, and extensive code restructuring. New features include dynamic-memory management, scattering-routine integration, a new initial-condition module, and reviewed post-processing methods. Existing features like on-line aperture checking and Fluka-coupling are now enabled by default. Extensive performance regression tests have been developed and deployed as part of the new-release generation. The new features of the tracking environment developed for the massive numerical simulations will be discussed as well

SixTrack Version 5: Status and New Developments

SixTrack Version 5 is a major SixTrack release that introduces new features, with improved integration of the existing ones, and extensive code restructuring. New features include dynamic-memory management, scattering-routine integration, a new initial-condition module, and reviewed post-processing methods. Existing features like on-line aperture checking and Fluka-coupling are now enabled by default. Extensive performance regression tests have been developed and deployed as part of the new-release generation. The new features of the tracking environment developed for the massive numerical simulations will be discussed as well

Beam dynamics issues in the FCC

International audienceThe international Future Circular Collider (FCC) study is designing hadron, lepton and lepton-hadron colliders based on a new 100 km tunnel in the Geneva region. The main focus and ultimate goal of the study are high-luminosity proton-proton collisions at a centre-of-mass energy of 100 TeV, using 16 T Nb3Sn dipole magnets. Specific FCC beam dynamics issues are related to the large circumference, the high brightness - made available by radiation damping -, the small geometric emittance, unprecedented collision energy and luminosity, the huge amount of energy stored in the beam, large synchrotron radiation power, plus the injection scenarios. In addition to the FCC-hh proper, also a High-Energy LHC (HE-LHC) is being explored, using the FCC-hh magnet technology in the existing LHC tunnel, which can yield a centre-of-mass energy around 25 TeV

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients