Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Diamagnetic cavity at comet 67P/Churyumov-Gerasimenko: plasma characteristics and dynamics

International audienceThe flux gate magnetometer under the Rosetta plasma consortium (RPC-MAG) onboard the Rosetta orbiter identified a large number of unmagnetized plasma regions around the expanding cometary ionosphere of the comet 67P/Churyumov-Gerasimenko. The coupling between the cometary plasma and neutral gas through ion-neutral and electron-neutral collisions leads to these "diamagnetic cavities" within which the solar wind magnetic field cannot penetrate. In the present work we will study the electron density measurements from the mutual impedance probe (RPC-MIP) to characterize the structure and dynamics of these unmagnetized inner cometary plasma regions. It is observed that these are particularly homogeneous, compared to the highly dynamical magnetized plasmas observed in adjacent magnetized regions. Moreover, during the crossings of multiple, successive diamagnetic regions over time scales of tens of minutes to hours, the plasma density is almost identical in the different unmagnetized regions, suggesting that these unmagnetized regions may be a single diamagnetic structure crossed several times by Rosetta. About 15% of the unmagnetized plasma regions are found to be characterized by dynamic plasma enhancements over the stable background neutral gas variation. Detailed analyses on the plasma characteristics of the diamagnetic cavities and the plasma enhancements within them will be presented in the paper

Diamagnetic cavity at comet 67P/Churyumov-Gerasimenko: plasma characteristics and dynamics

International audienceThe flux gate magnetometer under the Rosetta plasma consortium (RPC-MAG) onboard the Rosetta orbiter identified a large number of unmagnetized plasma regions around the expanding cometary ionosphere of the comet 67P/Churyumov-Gerasimenko. The coupling between the cometary plasma and neutral gas through ion-neutral and electron-neutral collisions leads to these "diamagnetic cavities" within which the solar wind magnetic field cannot penetrate. In the present work we will study the electron density measurements from the mutual impedance probe (RPC-MIP) to characterize the structure and dynamics of these unmagnetized inner cometary plasma regions. It is observed that these are particularly homogeneous, compared to the highly dynamical magnetized plasmas observed in adjacent magnetized regions. Moreover, during the crossings of multiple, successive diamagnetic regions over time scales of tens of minutes to hours, the plasma density is almost identical in the different unmagnetized regions, suggesting that these unmagnetized regions may be a single diamagnetic structure crossed several times by Rosetta. About 15% of the unmagnetized plasma regions are found to be characterized by dynamic plasma enhancements over the stable background neutral gas variation. Detailed analyses on the plasma characteristics of the diamagnetic cavities and the plasma enhancements within them will be presented in the paper

Ion composition at comet 67P near perihelion: Rosetta observations and model-based interpretation

International audienceWe present the ion composition in the coma of comet 67P with newly detected ion species over the 28 to 37 u mass range, probed by Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA)/Double Focusing Mass Spectrometer (DFMS). In summer 2015, the nucleus reached its highest outgassing rate and ion-neutral reactions started to take place at low cometocentric distances. Minor neutrals can efficiently capture protons from the ion population, making the protonated version of these neutrals a major ion species. So far, only NH>sup>+4 has been reported at comet 67P. However, there are additional neutral species with proton affinities higher than that of water (besides NH3) that have been detected in the coma of comet 67P: CH3OH, HCN, H2CO and H2S. Their protonated versions have all been detected. Statistics showing the number of detections with respect to the number of scans are presented. The effect of the negative spacecraft potential probed by the Rosetta Plasma Consortium (RPC)/LAngmuir Probe (LAP) on ion detection is assessed. An ionospheric model has been developed to assess the different ion density profiles and compare them to the ROSINA/DFMS measurements. It is also used to interpret the ROSINA/DFMS observations when different ion species have similar masses, and their respective densities are not high enough to disentangle them using the ROSINA/DFMS high resolution mode. The different ion species that have been reported in the coma of 67P are summarised and compared with the ions detected at comet 1P/Halley during the Giotto mission