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

Indirect effects may buffer negative responses of seagrass invertebrate communities to ocean acidification

Ocean acidification has been shown to have highly variable effects, with many negative and some positive responses from individual species, while community level effects are largely unknown. Although an overall loss of biodiversity is expected, predicting the effects of ocean acidification on whole assemblages can be problematic as both direct and indirect effects of acidification must be taken into consideration. This study demonstrates how invertebrate assemblages associated with the highly productive seagrass, Posidonia oceanica, respond to natural acidification that occurs at CO2 vents off the coast of Italy. We examined seasonal differences in invertebrate community structure between two distinct pH zones: control (pH 8.1) and acidified (pH 7.8) and show that many groups of invertebrate taxa were robust to acidification effects. Differences in community struc- ture appeared to be driven by the indirect effects of acidification, such as changes to canopy structure and food availability, rather than physiological intolerance to low pH. The number of invertebrates collected in acidified stations was almost double that of control stations during the study and many heavily calcified species appeared to thrive. These results highlight how positive indirect effects may buffer the ecological impacts of acidification, and provide evidence that this highly productive, nearshore habitat may provide refuge to its associated commu- nities from future ocean acidification

Identifying potential high-risk zones for land-derived plastic litter to marine megafauna and key habitats within the North Atlantic

The pervasive use of plastic in modern society has led to plastic litter becoming ubiquitous within the ocean. Land-based sources of plastic litter are thought to account for the majority of plastic pollution in the marine environment, with plastic bags, bottles, wrappers, food containers and cutlery among the most common items found. In the marine environment, plastic is a transboundary pollutant, with the potential to cause damage far beyond the political borders from where it originated, making the management of this global pollutant particularly complex. In this study, the risks of land-derived plastic litter (LDPL) to major groups of marine megafauna – seabirds, cetaceans, pinnipeds, elasmobranchs, turtles, sirenians, tuna and billfish – and a selection of productive and biodiverse biogenic habitats – coral reefs, mangroves, seagrass, saltmarsh and kelp beds – were analysed using a Spatial Risk Assessment approach. The approach combines metrics for vulnerability (mechanism of harm for megafauna group or habitat), hazard (plastic abundance) and exposure (distribution of group or habitat). Several potential high-risk zones (HRZs) across the North Atlantic were highlighted, including the Azores, the UK, the French and US Atlantic coasts, and the US Gulf of Mexico. Whilst much of the modelled LDPL driving risk in the UK originated from domestic sources, in other HRZs, such as the Azores archipelago and the US Gulf of Mexico, plastic originated almost exclusively from external (non-domestic) sources. LDPL from Caribbean islands - some of the largest generators of marine plastic pollution in the dataset of river plastic emissions used in the study - was noted as a significant input to HRZs across both sides of the Atlantic. These findings highlight the potential of Spatial Risk Assessment analyses to determine the location of HRZs and understand where plastic debris monitoring and management should be prioritised, enabling more efficient deployment of interventions and mitigation measures.</p

Biological impacts of ocean acidification: a postgraduate perspective on research priorities

Research into the effects of ocean acidification (OA) on marine organisms has greatly increased during the past decade, as realization of the potential dramatic impacts has grown. Studies have revealed the multifarious responses of organisms to OA conditions, indicating a high level of intra- and interspecific variation in species’ ability to accommodate these alterations. If we are to provide policy makers with sound, scientific input regarding the expected consequences of OA, we need a broader understanding of these predicted changes. As a group of 20 multi-disciplinary postgraduate students from around the globe, with a study focus on OA, we are a strong representation of ‘next generation’ scientists in this field. In this unique cumulative paper, we review knowledge gaps in terms of assessing the biological impacts of OA, outlining directions for future research