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

Functional characterization of olfactory binding proteins for appeasing compounds and molecular cloning in the vomeronasal organ of pre-pubertal pigs.

International audienceThe appeasing behaviour of pre-pubertal pigs appears to result from the perception of maternal odours (fatty acids) and of steroids coming from the male. We have used a ligand-oriented approach to functionally characterize olfactory binding proteins involved in the detection of appeasing compounds in the nasal mucosa (NM) and the vomeronasal organ (VNO) of pre-pubertal pigs. Several proteins were identified, combining binding assay, immunodetection and protein sequencing. Their sites of expression in nasal and vomeronasal tissues were studied by reverse transcription polymerase chain reaction (RT-PCR). The proteins belong to the lipocalin superfamily: Alpha-1-acid glycoprotein (AGP), odorant-binding protein (OBP), salivary lipocalin (SAL) and Von Ebner's gland protein (VEG), and displayed different binding capacities for the appeasing compounds. RT-PCR experiments showed that OBP and VEG are expressed not only in the NM, but also in the VNO and that SAL is only expressed in the VNO. This is the first report of the expression of these lipocalins in the VNO. Different binding affinities between lipocalins and appeasing compounds, together with their different localizations in the olfactory systems, suggest multiple possibilities for the peripheral coding of appeasing signals

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

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