Time to negative PCR conversion amongst high-risk patients with mild-to-moderate Omicron BA.1 and BA.2 COVID-19 treated with sotrovimab or nirmatrelvir.

OBJECTIVES: Our aim was to compare the clinical and virological outcomes in Omicron BA.1- and BA.2-infected patients who received sotrovimab with those in patients who received nirmatrelvir for the prevention of severe COVID-19. METHODS: In this multi-centric, prospective ANRS 0003S CoCoPrev cohort study, patients at a high risk of progression of mild-to-moderate BA.1 or BA.2 COVID-19 who received sotrovimab or nirmatrelvir were included. The proportion of patients with progression to severe COVID-19, time between the start of treatment to negative PCR conversion, SARS-CoV-2 viral decay, and characterization of resistance variants were determined. A multi-variable Cox proportional hazard model was used to determine the time to negative PCR conversion and a mixed-effect model for the dynamics of viral decay. RESULTS: Amongst 255 included patients, 199 (80%) received ≥3 vaccine doses, 195 (76%) received sotrovimab, and 60 (24%) received nirmatrelvir. On day 28, new COVID-19-related hospitalization occurred in 4 of 193 (2%; 95% CI, 1-5%) sotrovimab-treated patients and 0 of 55 nirmatrelvir-treated patients (p 0.24). One out of the 55 nirmatrelvir-treated patients died (2%; 95% CI, 0-10%). The median time to negative PCR conversion was 11.5 days (95% CI, 10.5-13) in the sotrovimab-treated patients vs. 4 days (95% CI, 4-9) in the nirmatrelvir-treated patients (p < 0.001). Viral decay was faster in the patients who received nirmatrelvir (p < 0.001). In the multi-variable analysis, nirmatrelvir and nasopharyngeal PCR cycle threshold values were independently associated with faster conversion to negative PCR (hazard ratio, 2.35; 95% CI, 1.56-3.56; p < 0.0001 and hazard ratio, 1.05; 95% CI, 1.01-1.08; p 0.01, respectively). CONCLUSIONS: Early administration of nirmatrelvir in high-risk patients compared with that of sotrovimab was associated with faster viral clearance. This may participate to decrease transmission and prevent viral resistance.

Construction and evaluation of an α-particle-irradiation exposure apparatus.

PURPOSE: The development of an exposure apparatus for in situ α-irradiation studies of cells. The construction of the apparatus is simple and the apparatus is maintenance free, easy to use and of low cost. This small device can be placed in an incubator, where the exposure environment is controlled. Moreover the vapor saturated incubator protects the cells from drying out, allowing long irradiation intervals. MATERIALS AND METHODS: The system includes a 234U alpha (α)-source of total activity 0.77 ± 0.03 MBq in the form of a thin disk deposited on an aluminum substrate. The α-particles emitted in the air have a mean energy of 4.9 MeV at the disk surface. Source homogeneity has been studied via Rutherford Backscattering Spectrometry. Using SRIM 2013 and Monte Carlo (MC) simulations via the MCNP6.1 code, LET and energy deposition values have been calculated for various filling gasses. Furthermore, based on these simulations, the assembly's dimensions and equivalent irradiation rate have been determined. With respect to the aforementioned dimensions, the experimental setup is constructed in a way to provide uniform irradiation of the sample. Using Sacalc3v1.4 irradiation radial homogeneity has been studied. In order to evaluate biologically our apparatus, a well-established chromosomal aberration assay has been utilized, applied in exponentially growing hamster (CHO) cells. Furthermore, immunofluorescence gamma-H2AX/53BP1 foci assay has been performed as a 'biological detector', in order to validate α-particles surface density. RESULTS: Source surface homogeneity: emission deviations do not exceed 10-15%. The optimal distance between the source and the cells for irradiation is determined to be 14.8 mm. Irradiation radial homogeneity: a deviation of 5% occurs at the first 8 mm from the center of the irradiation area, and a 10% deviation occurs after 12 mm. Chromosomal aberrations were found in good agreement with the corresponding in bibliography. CONCLUSIONS: The current technical report describes analytically the development and evaluation stages of this experimental housing; from MC simulations to the irradiation of mammalian cells and data analysis. Moreover, guidance is provided as well as a report of the variables on which critical parameters are depended, so as to make this work useful to anyone who wants to construct a similar in-house α-irradiation apparatus for radiobiological studies using mammalian cells.