Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice

The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2

Gaia Data Release 1. Astrometry: one billion positions, two million proper motions and parallaxes

Context. Gaia Data Release 1 (DR1) contains astrometric results for more than 1 billion stars brighter than magnitude 20.7 based on observations collected by the Gaia satellite during the first 14 months of its operational phase. Aims. We give a brief overview of the astrometric content of the data release and of the model assumptions, data processing, and validation of the results. Methods. For stars in common with the Hipparcos and Tycho-2 catalogues, complete astrometric single-star solutions are obtained by incorporating positional information from the earlier catalogues. For other stars only their positions are obtained, essentially by neglecting their proper motions and parallaxes. The results are validated by an analysis of the residuals, through special validation runs, and by comparison with external data. Results. For about two million of the brighter stars (down to magnitude ∼11.5) we obtain positions, parallaxes, and proper motions to Hipparcos-type precision or better. For these stars, systematic errors depending for example on position and colour are at a level of ±0.3 milliarcsecond (mas). For the remaining stars we obtain positions at epoch J2015.0 accurate to ∼10 mas. Positions and proper motions are given in a reference frame that is aligned with the International Celestial Reference Frame (ICRF) to better than 0.1 mas at epoch J2015.0, and non-rotating with respect to ICRF to within 0.03 mas yr−1 . The Hipparcos reference frame is found to rotate with respect to the Gaia DR1 frame at a rate of 0.24 mas yr−1 . Conclusions. Based on less than a quarter of the nominal mission length and on very provisional and incomplete calibrations, the quality and completeness of the astrometric data in Gaia DR1 are far from what is expected for the final mission products. The present results nevertheless represent a huge improvement in the available fundamental stellar data and practical definition of the optical reference frame

Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution

Gaia data release 1. Pre-processing and source list creation

Context. The first data release from the Gaia mission contains accurate positions and magnitudes for more than a billion sources, and proper motions and parallaxes for the majority of the 2.5 million Hipparcos and Tycho-2 stars. Aims. We describe three essential elements of the initial data treatment leading to this catalogue: the image analysis, the construction of a source list, and the near real-time monitoring of the payload health. We also discuss some weak points that set limitations for the attainable precision at the present stage of the mission. Methods. Image parameters for point sources are derived from one-dimensional scans, using a maximum likelihood method, under the assumption of a line spread function constant in time, and a complete modelling of bias and background. These conditions are, however, not completely fulfilled. The Gaia source list is built starting from a large ground-based catalogue, but even so a significant number of new entries have been added, and a large number have been removed. The autonomous onboard star image detection will pick up many spurious images, especially around bright sources, and such unwanted detections must be identified. Another key step of the source list creation consists in arranging the more than 1010 individual detections in spatially isolated groups that can be analysed individually. Results. Complete software systems have been built for the Gaia initial data treatment, that manage approximately 50 million focal plane transits daily, giving transit times and fluxes for 500 million individual CCD images to the astrometric and photometric processing chains. The software also carries out a successful and detailed daily monitoring of Gaia health

Gaia data release 1. Pre-processing and source list creation

Context. The first data release from the Gaia mission contains accurate positions and magnitudes for more than a billion sources, and proper motions and parallaxes for the majority of the 2.5 million Hipparcos and Tycho-2 stars. Aims. We describe three essential elements of the initial data treatment leading to this catalogue: the image analysis, the construction of a source list, and the near real-time monitoring of the payload health. We also discuss some weak points that set limitations for the attainable precision at the present stage of the mission. Methods. Image parameters for point sources are derived from one-dimensional scans, using a maximum likelihood method, under the assumption of a line spread function constant in time, and a complete modelling of bias and background. These conditions are, however, not completely fulfilled. The Gaia source list is built starting from a large ground-based catalogue, but even so a significant number of new entries have been added, and a large number have been removed. The autonomous onboard star image detection will pick up many spurious images, especially around bright sources, and such unwanted detections must be identified. Another key step of the source list creation consists in arranging the more than 1010 individual detections in spatially isolated groups that can be analysed individually. Results. Complete software systems have been built for the Gaia initial data treatment, that manage approximately 50 million focal plane transits daily, giving transit times and fluxes for 500 million individual CCD images to the astrometric and photometric processing chains. The software also carries out a successful and detailed daily monitoring of Gaia health

Gaia Data Release 1. Open cluster astrometry: performance, limitations, and future prospects

Context. The first Gaia Data Release contains the Tycho-Gaia Astrometric Solution (TGAS). This is a subset of about 2 million stars for which, besides the position and photometry, the proper motion and parallax are calculated using Hipparcos and Tycho-2 positions in 1991.25 as prior information. Aims. We investigate the scientific potential and limitations of the TGAS component by means of the astrometric data for open clusters. Methods. Mean cluster parallax and proper motion values are derived taking into account the error correlations within the astrometric solutions for individual stars, an estimate of the internal velocity dispersion in the cluster, and, where relevant, the e ects of the depth of the cluster along the line of sight. Internal consistency of the TGAS data is assessed. Results. Values given for standard uncertainties are still inaccurate and may lead to unrealistic unit-weight standard deviations of least squares solutions for cluster parameters. Reconstructed mean cluster parallax and proper motion values are generally in very good agreement with earlier Hipparcos-based determination, although the Gaia mean parallax for the Pleiades is a significant exception. We have no current explanation for that discrepancy. Most clusters are observed to extend to nearly 15 pc from the cluster centre, and it will be up to future Gaia releases to establish whether those potential cluster-member stars are still dynamically bound to the clusters. Conclusions. The Gaia DR1 provides the means to examine open clusters far beyond their more easily visible cores, and can provide membership assessments based on proper motions and parallaxes. A combined HR diagram shows the same features as observed before using the Hipparcos data, with clearly increased luminosities for older A and F dwarfs

Gaia Data Release 1. Open cluster astrometry: performance, limitations, and future prospects

Context. The first Gaia Data Release contains the Tycho-Gaia Astrometric Solution (TGAS). This is a subset of about 2 million stars for which, besides the position and photometry, the proper motion and parallax are calculated using Hipparcos and Tycho-2 positions in 1991.25 as prior information. Aims. We investigate the scientific potential and limitations of the TGAS component by means of the astrometric data for open clusters. Methods. Mean cluster parallax and proper motion values are derived taking into account the error correlations within the astrometric solutions for individual stars, an estimate of the internal velocity dispersion in the cluster, and, where relevant, the e ects of the depth of the cluster along the line of sight. Internal consistency of the TGAS data is assessed. Results. Values given for standard uncertainties are still inaccurate and may lead to unrealistic unit-weight standard deviations of least squares solutions for cluster parameters. Reconstructed mean cluster parallax and proper motion values are generally in very good agreement with earlier Hipparcos-based determination, although the Gaia mean parallax for the Pleiades is a significant exception. We have no current explanation for that discrepancy. Most clusters are observed to extend to nearly 15 pc from the cluster centre, and it will be up to future Gaia releases to establish whether those potential cluster-member stars are still dynamically bound to the clusters. Conclusions. The Gaia DR1 provides the means to examine open clusters far beyond their more easily visible cores, and can provide membership assessments based on proper motions and parallaxes. A combined HR diagram shows the same features as observed before using the Hipparcos data, with clearly increased luminosities for older A and F dwarfs

Gaia Data Release 1. Astrometry: one billion positions, two million proper motions and parallaxes

Context. Gaia Data Release 1 (DR1) contains astrometric results for more than 1 billion stars brighter than magnitude 20.7 based on observations collected by the Gaia satellite during the first 14 months of its operational phase. Aims. We give a brief overview of the astrometric content of the data release and of the model assumptions, data processing, and validation of the results. Methods. For stars in common with the Hipparcos and Tycho-2 catalogues, complete astrometric single-star solutions are obtained by incorporating positional information from the earlier catalogues. For other stars only their positions are obtained, essentially by neglecting their proper motions and parallaxes. The results are validated by an analysis of the residuals, through special validation runs, and by comparison with external data. Results. For about two million of the brighter stars (down to magnitude ∼11.5) we obtain positions, parallaxes, and proper motions to Hipparcos-type precision or better. For these stars, systematic errors depending for example on position and colour are at a level of ±0.3 milliarcsecond (mas). For the remaining stars we obtain positions at epoch J2015.0 accurate to ∼10 mas. Positions and proper motions are given in a reference frame that is aligned with the International Celestial Reference Frame (ICRF) to better than 0.1 mas at epoch J2015.0, and non-rotating with respect to ICRF to within 0.03 mas yr−1 . The Hipparcos reference frame is found to rotate with respect to the Gaia DR1 frame at a rate of 0.24 mas yr−1 . Conclusions. Based on less than a quarter of the nominal mission length and on very provisional and incomplete calibrations, the quality and completeness of the astrometric data in Gaia DR1 are far from what is expected for the final mission products. The present results nevertheless represent a huge improvement in the available fundamental stellar data and practical definition of the optical reference frame

Gaia Data Release 1. Astrometry: one billion positions, two million proper motions and parallaxes

Context. Gaia Data Release 1 (DR1) contains astrometric results for more than 1 billion stars brighter than magnitude 20.7 based on observations collected by the Gaia satellite during the first 14 months of its operational phase. Aims. We give a brief overview of the astrometric content of the data release and of the model assumptions, data processing, and validation of the results. Methods. For stars in common with the Hipparcos and Tycho-2 catalogues, complete astrometric single-star solutions are obtained by incorporating positional information from the earlier catalogues. For other stars only their positions are obtained, essentially by neglecting their proper motions and parallaxes. The results are validated by an analysis of the residuals, through special validation runs, and by comparison with external data. Results. For about two million of the brighter stars (down to magnitude ∼11.5) we obtain positions, parallaxes, and proper motions to Hipparcos-type precision or better. For these stars, systematic errors depending for example on position and colour are at a level of ±0.3 milliarcsecond (mas). For the remaining stars we obtain positions at epoch J2015.0 accurate to ∼10 mas. Positions and proper motions are given in a reference frame that is aligned with the International Celestial Reference Frame (ICRF) to better than 0.1 mas at epoch J2015.0, and non-rotating with respect to ICRF to within 0.03 mas yr−1 . The Hipparcos reference frame is found to rotate with respect to the Gaia DR1 frame at a rate of 0.24 mas yr−1 . Conclusions. Based on less than a quarter of the nominal mission length and on very provisional and incomplete calibrations, the quality and completeness of the astrometric data in Gaia DR1 are far from what is expected for the final mission products. The present results nevertheless represent a huge improvement in the available fundamental stellar data and practical definition of the optical reference frame