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

Geomicrobiological Changes in Two Ephemeral Desert Playa Lakes in the Western United States

The geochemistry and microbiology of two ephemeral playa lakes in the Western United States, Surprise Valley Alkali Lake (SVAL) and Eldorado Playa (EP), were examined over one wetting cycle, revealing dramatic temporal changes in suspended mineralogy, aqueous chemistry, and bacterial populations. In SVAL the predominant suspended mineral changed from smectite to vermiculite and clinoptilolite, which led to a depletion of soluble Mg2+. Nitrate became depleted in both playas as a result of biological nitrogen demand imparted by unusually dense microbial communities reaching 1 × 108 cultivable heterotrophs per ml of water. One hundred eighty eight bacterial isolates were obtained, representing sixty phylotypes and four phyla: Actinobacteria, Bacteroidetes, Proteobacteria, and Firmicutes. Phylogenetic analyses suggested that the microbial communities reflected different phases of succession, with SVAL changing from a diverse community with abundant Yonghaparkia to a less diverse late summer community with abundant Bacteroidetes and Proteobacteria such as Loktanella, Rhodobaca, Saccharospirillum, Flexibacter, and phylogenetically novel members of the Flexibacteriaceae. In EP, a diverse assemblage of bacteria often associated with soils was replaced very quickly by a much less even community dominated by Yonghaparkia, Sandarakinorhabdus, and relatives of Belliella baltica. Strikingly, the early summer microbial community from SVAL was not significantly different from the EP community that developed within one week of flooding, even though these playas are almost 1000 km apart, whereas sympatric communities in different phases of succession were different. To our knowledge, this is one of the first geomicrobiological studies of a recharge playa, the dominant playa type worldwide

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc