Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron variant of concern

Background: Recent in-vitro data have shown that the activity of monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies according to the variant of concern (VOC). No studies have compared the clinical efficacy of different mAbs against Omicron VOC. Methods: The MANTICO trial is a non-inferiority randomised controlled trial comparing the clinical efficacy of early treatments with bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab in outpatients aged 50 or older with mild-to-moderate SARS-CoV-2 infection. As the patient enrolment was interrupted for possible futility after the onset of the Omicron wave, the analysis was performed according to the SARS-CoV-2 VOC. The primary outcome was coronavirus disease 2019 (COVID-19) progression (hospitalisation, need of supplemental oxygen therapy, or death through day 14). Secondary outcomes included the time to symptom resolution, assessed using the product-limit method. Kaplan-Meier estimator and Cox proportional hazard model were used to assess the association with predictors. Log rank test was used to compare survival functions. Results: Overall, 319 patients were included. Among 141 patients infected with Delta, no COVID-19 progression was recorded, and the time to symptom resolution did not differ significantly between treatment groups (Log-rank Chi-square 0.22, p 0.90). Among 170 patients infected with Omicron (80.6% BA.1 and 19.4% BA.1.1), two COVID-19 progressions were recorded, both in the bamlanivimab/etesevimab group, and the median time to symptom resolution was 5 days shorter in the sotrovimab group compared with the bamlanivimab/etesevimab and casirivimab/imdevimab groups (HR 0.53 and HR 0.45, 95% CI 0.36-0.77 and 95% CI 0.30-0.67, p<0.01). Conclusions: Our data suggest that, among adult outpatients with mild-to-moderate SARS-CoV-2 infection due to Omicron BA.1 and BA.1.1, early treatment with sotrovimab reduces the time to recovery compared with casirivimab/imdevimab and bamlanivimab/etesevimab. In the same population, early treatment with casirivimab/imdevimab may maintain a role in preventing COVID-19 progression. The generalisability of trial results is substantially limited by the early discontinuation of the trial and firm conclusions cannot be drawn. Funding: This trial was funded by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The VOC identification was funded by the ORCHESTRA (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic) project, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement number 101016167. Clinical trial number: NCT05205759

Search for CP violation in D0 and D+ decays

A high statistics sample of photoproduced charm particles from the FOCUS (E831) experiment at Fermilab has been used to search for CP violation in the Cabibbo suppressed decay modes D+ to K-K+pi+, D0 to K-K+ and D0 to pi-pi+. We have measured the following CP asymmetry parameters: A_CP(K-K+pi+) = +0.006 +/- 0.011 +/- 0.005, A_CP(K-K+) = -0.001 +/- 0.022 +/- 0.015 and A_CP(pi-pi+) = +0.048 +/- 0.039 +/- 0.025 where the first error is statistical and the second error is systematic. These asymmetries are consistent with zero with smaller errors than previous measurements.Comment: 12 pages, 4 figure

Search for CP violation in D0 and D+ decays

A high statistics sample of photoproduced charm particles from the FOCUS (E831) experiment at Fermilab has been used to search for CP violation in the Cabibbo suppressed decay modes D+ to K-K+pi+, D0 to K-K+ and D0 to pi-pi+. We have measured the following CP asymmetry parameters: A_CP(K-K+pi+) = +0.006 +/- 0.011 +/- 0.005, A_CP(K-K+) = -0.001 +/- 0.022 +/- 0.015 and A_CP(pi-pi+) = +0.048 +/- 0.039 +/- 0.025 where the first error is statistical and the second error is systematic. These asymmetries are consistent with zero with smaller errors than previous measurements.Comment: 12 pages, 4 figure

A measurement of lifetime differences in the neutral D-meson system

Using a high statistics sample of photoproduced charm particles from the FOCUS experiment at Fermilab, we compare the lifetimes of neutral D mesons decaying via D0 to K- pi+ and K- K+ to measure the lifetime differences between CP even and CP odd final states. These measurements bear on the phenomenology of D0 - D0bar mixing. If the D0 to K-pi+ is an equal mixture of CP even and CP odd eigenstates, we measure yCP = 0.0342 \pm 0.0139 \pm 0.0074.Comment: 15 pages, 5 figure

Measurements of the Sigma_c^0 and Sigma_c^{++} Mass Splittings

Using a high statistics sample of photoproduced charmed particles from the FOCUS experiment at Fermilab (FNAL-E831), we measure the mass splittings of the charmed baryons Sigma_c^0 and Sigma_c^{++}. We find M(Sigma_c^0 - Lambda_c^+) = 167.38 +/- 0.21 +/- 0.13 MeV/c^2 and M(Sigma_c^++ - Lambda_c^+) = 167.35 +/- 0.19 +/- 0.12 MeV/c^2 with samples of 362 +/- 36 and 461 +/- 39 events, respectively. We measure the isospin mass splitting M(Sigma_c^++ - Sigma_c^0) to be -0.03 +/- 0.28 +/- 0.11 Mev/c^2. The first errors are statistical and the second are systematic.Comment: 10 pages, 2 figure

New FOCUS results on charm mixing and CP violation

We present a summary of recent results on CP violation and mixing in the charm quark sector based on a high statistics sample collected by photoproduction experiment FOCUS (E831 at Fermilab). We have measured the difference in lifetimes for the $D^0$ decays: $D^0 \to K^-\pi^+$ and $D^0 \to K^-K^+$. This translates into a measurement of the $y_{CP}$ mixing parameter in the \d0d0 system, under the assumptions that $K^-K^+$ is an equal mixture of CP odd and CP even eigenstates, and CP violation is negligible in the neutral charm meson system. We verified the latter assumption by searching for a CP violating asymmetry in the Cabibbo suppressed decay modes $D^+ \to K^-K^+\pi^+$, $D^0 \to K^-K^+$ and $D^0 \to \pi^-\pi^+$. We show preliminary results on a measurement of the branching ratio $\Gamma(D^{*+}\to \pi^+ (K^+\pi^-))/\Gamma(D^{*+}\to \pi^+ (K^-\pi^+))$.Comment: 9 pages, 6 figures, requires espcrc2.sty. Presented by S.Bianco at CPConf2000, September 2000, Ferrara (Italy). In this revision, fixed several stylistic flaws, add two significant references, fixed a typo in Tab.

Brixsino High-Flux Dual X-Ray and THz Radiation Source Based on Energy Recovery Linacs

We present the conceptual design of a compact light source named BriXSinO. BriXSinO was born as demonstrator of the Marix project, but it is also a dual high flux radiation source Inverse Compton Source (ICS) of X-ray and Free-Electron Laser of THz spectral range radiation conceived for medical applications and general applied research. The accelerator is a push-pull CW-SC Energy Recovery Linac (ERL) based on superconducting cavities technology and allows to sustain MW-class beam power with almost just one hundred kW active power dissipation/consumption. ICS line produces 33 keV monochromatic X-Rays via Compton scattering of the electron beam with a laser system in Fabry-Pérot cavity at a repetition rate of 100 MHz. The THz FEL oscillator is based on an undulator imbedded in optical cavity and generates THz wavelengths from 15 to 50 micron

MariX, an advanced MHz-class repetition rate X-ray source for linear regime time-resolved spectroscopy and photon scattering

The need of a fs-scale pulsed, high repetition rate, X-ray source for time-resolved fine analysis of matter (spectroscopy and photon scattering) in the linear response regime is addressed by the conceptual design of a facility called MariX (Multi-disciplinary Advanced Research Infrastructure for the generation and application of X-rays) outperforming current X-ray sources for the declared scope. MariX is based on the original design of a two-pass two-way superconducting linear electron accelerator, equipped with an arc compressor, to be operated in CW mode (1 MHz). MariX provides FEL emission in the range 0.2–8 keV with 108 photons per pulse ideally suited for photoelectric effect and inelastic X-ray scattering experiments. The accelerator complex includes an early stage that supports an advanced inverse Compton source of very high-flux hard X-rays of energies up to 180 keV that is well adapted for large area radiological imaging, realizing a broad science programme and serving a multidisciplinary user community, covering fundamental science of matter and application to life sciences, including health at preclinical and clinical level