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

Diurnal variation in the water-soluble inorganic ions, organic carbon and isotopic compositions of total carbon and nitrogen in biomass burning aerosols from the LBA-SMOCC campaign in Rondônia, Brazil

Aerosol particles (PM2.5) were collected during the day (n=6) and nighttime (n=9) from a tropical pasture site in Rondônia, Brazil during an intensive biomass burning period (16-26 September, 2002). Higher normalized (by K+, levoglucosan, or apparent elemental carbon, ECa) mass concentrations of SO4^[2-] and CH3SO3- in daytime suggest their photochemical production, while the opposite trend for NO3- suggests its transfer to the aerosol phase at lower temperatures and higher humidities, as well as possibly production through hydrolysis of N2O5 on aqueous aerosol particles. About 4.2-7.5% of OC (5-13% of water-soluble organic carbon (WSOC)) could be characterized at the molecular level using GC-MS and GC-FID. Among the detected organic compound classes, the relative abundances of anhydrosugars and aromatics were higher in night samples, but sugars/sugar alcohols, diacids, oxoacids and α-dicarbonyls were more abundant in day samples. Consecutive day and night samples showed that δ13C values of total carbon (TC) were lower in daytime samples, which can be interpreted as resulting from higher contributions of refractory TC depleted in 13C due to predominantly flaming combustion. The δ15N values of total nitrogen (TN) ranged from +23.5‰ to +25.7‰, however, there was no trend in day and night samples. Higher values of δ13C and δ15N for biomass burning particles than those of unburned vegetation reflect positive isotopic enrichment either during the formation of particles or after the emission of particles in the atmosphere

Comparison of Amazonian biomass burning and East Asian marine aerosols : Bulk organics, diacids and related compounds, water-soluble inorganic ions, stable carbon and nitrogen isotope ratios

In this study, biomass burning and marine aerosols collected in the Amazon, Brazil and on an island south of South Korea are compared in terms of chemical characteristics and ageing by the determination of water-soluble organic carbon (WSOC), water-insoluble organic carbon (WIOC), elemental carbon (EC), diacids (C2-C11) and related compounds (ketoacids and α-dicarbonyls), stable carbon isotopic ratios (δ13C) of total carbon (TC), and nitrogen isotopic ratios (δ15N) of total nitrogen (TN). The concentration ratios of WSOC, WIOC, and EC to aerosol mass are 2-12 times higher in biomass burning aerosols than in marine aerosols. In contrast, concentration ratios of water-soluble cations and anions to aerosol mass are lower by a factor of 0.2-0.6 in biomass burning aerosols than in marine aerosols. Among diacids and related compounds, oxalic acid (C2) was found to be the most abundant, followed by succinic acid (C4) in biomass burning aerosols, while malonic acid (C3) dominated in marine aerosols. Lower relative abundances of C2-C4 diacids, unsaturated diacids, and α-dicarbonyls in total diacids and related compounds were observed in biomass burning aerosols than in marine aerosols, whereas those of C5-C11 diacids, branched diacids, multifunctional diacids, and ketoacids were higher in biomass burning aerosols. These results suggest that there are significant differences in the sources and photochemical production pathways of individual diacids and related compounds. While the δ13C values (－26.5 to －20.5‰) of TC and δ15N values (＋6.8 to ＋26.9 ‰) of TN showed a large variation in marine aerosols, the variations were rather small (δ13C:－26.1 to －23.6‰; δ15N: ＋21.5 to ＋25.7‰) in biomass-burning aerosols. We propose that these δ13C and δ15N values can be used to characterize biomass-burning aerosols

Interrelationships Between Aerosol Characteristics and Light Scattering During Late-winter in a Eastern Mediterranean Arid Environment

An intensive field campaign involving measurement of various aerosol physical, chemical, and radiative properties was conducted at Sde Boker in the Negev Desert of Israel, from 18 February to 15 March 1997. Nephelometer measurements gave average background scattering coefficient values of about 25 M/m at 550 nm wavelength, but strong dust events caused the value of this parameter to rise up to about 800 M/m Backscattering fractions did not depend on aerosol loading, and generally fell in the range of 0.1 to 0.25, comparable to values reported for marine and Arctic environments. Chemical analysis of the aerosol revealed that, in the coarse size range (2 - 10 micrometer equivalent aerodynamic diameter (EAD)), calcium (Ca) was by far the most abundant element followed by silicon (Si), both of which are indicators for mineral dust. In the fine size fraction (< 2 micrometers EAD), sulfur (S) generally was the dominant element, except during high dust episodes when Ca and Si were again the most abundant. Furthermore, fine black carbon (BC) correlates with S, suggesting that they may have originated from the same sources or source regions. An indication of the short-term effect of aerosol loading on radiative forcing was provided by measurements of global and diffuse solar radiation, which showed that during high turbidity periods (strong dust events) almost all of the solar radiation reaching the area is scattered or absorbed