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

The relationship between inflammatory dietary pattern in childhood and depression in early adulthood

Background: Inflammation may be a hidden process in the relationship between dietary intake and depression, but no study has evaluated the role of diet and inflammation jointly in explaining depression risk in early life. The current study aims to investigate the relationship between inflammatory dietary pattern (IDP) in childhood and depression in early adulthood. Methods: This study used data prospectively collected over 10 years from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (n ​= ​6939) free from depression at baseline (age 8.5 years). An IDP score was empirically derived via reduced rank regression and stepwise linear regression based on dietary intake data from the food frequency questionnaire at 8.5 years and levels of inflammatory biomarkers, C-reactive protein and interleukin-6, at 9.5 years. At age 18 years, depression cases were identified via the International Statistical Classification of Diseases, 10th Revision (ICD-10) diagnosis and the Clinical Interview Schedule-Revised (CIS-R) depression score. Logistic regression models were constructed to examine the relationship between the IDP score and risk of depression adjusted for potential confounders. Analyses stratified by weight status were also conducted. Multiple imputations were utilized to minimize bias due to loss-to-follow-up. Results: Participants in the highest tertile of IDP score had 1.34 times odds to develop depression compared to those in the lowest tertile (95% CI, 1.08–1.66; P-trend<0.01), after dietary misreporting status and energy intake were adjusted. After all covariates were adjusted, the relationship between IDP tertiles and depression was attenuated (highest tertile vs. lowest tertile: OR ​= ​1.21; 95% CI, 0.96–1.51); in addition, the relationship was marginally significant among participants who were not overweight or obese (p ​< ​0.10) but not significant among participants who were overweight or obese. Conclusions: Higher IDP in childhood seems to be associated with higher depression risk in early adulthood. The study provides preliminary evidence that chronic inflammation may underlie the relationship between diet and depression even for children, especially those who are not overweight or obese