WNT9A Affects Late-Onset Acute Respiratory Distress Syndrome and 28-Day Survival: Evidence from a Three-Step Multiomics Study.

Late-onset (more than 48 h after ICU admission) acute respiratory distress syndrome (ARDS) is associated with shorter survival time and higher mortality; however, the underlying molecular targets remain unclear. As the WNT gene family is known to drive inflammation, immunity, and tissue fibrosis, all of which are closely related to the pathogenesis and prognosis of ARDS, we aim to investigate the associations of the WNT family with late-onset ARDS and 28-day survival. Genetic (n = 380), epigenetic (n = 185), transcriptional (n = 160), and protein (n = 300) data of patients with ARDS were extracted from the MEARDS (Molecular Epidemiology of ARDS) cohort. We used sure independence screening to identify late onset-related genetic biomarkers and constructed a genetic score on the basis of eight SNPs, which was associated with risk for late-onset ARDS (odds ratio [OR], 2.72; P = 3.81 × 10-14) and survival (hazard ratio [HR], 1.28; P = 0.008). The associations were further externally validated in the iSPAAR (Identification of SNPs Predisposing to Altered Acute Lung Injury Risk) (ORlate onset, 2.49 [P = 0.006]; HRsurvival, 1.87 [P = 0.045]) and MESSI (Molecular Epidemiology of Severe Sepsis in the ICU) (ORlate onset, 4.12 [P = 0.026]; HRsurvival, 1.45 [P = 0.036]) cohorts. Furthermore, we functionally interrogated the six mapped genes of eight SNPs in the multiomics data and noted associations of WNT9A (WNT family member 9A) in epigenetic (ORlate onset, 2.95 [P = 9.91 × 10-4]; HRsurvival, 1.53 [P = 0.011]) and protein (ORlate onset, 1.42 [P = 0.035]; HRsurvival, 1.38 [P = 0.011]) data. The mediation analysis indicated that the effects of WNT9A on ARDS survival were mediated by late onset (HRindirect, 1.12 [P = 0.014] for genetic data; HRindirect, 1.05 [P = 0.030] for protein data). The essential roles of WNT9A in immunity and fibrosis may explain the different trajectories of recovery and dysfunction between early- and late-onset ARDS, providing clues for ARDS treatment.

Retrospective Modeling of the Omicron Epidemic in Shanghai, China: Exploring the Timing and Performance of Control Measures.

BACKGROUND: In late February 2022, the Omicron epidemic swept through Shanghai, and the Shanghai government responded to it by adhering to a dynamic zero-COVID strategy. In this study, we conducted a retrospective analysis of the Omicron epidemic in Shanghai to explore the timing and performance of control measures based on the eventual size and duration of the outbreak. METHODS: We constructed an age-structured and vaccination-stratified SEPASHRD model by considering populations that had been detected or controlled before symptom onset. In addition, we retrospectively modeled the epidemic in Shanghai from 26 February 2022 to 31 May 2022 across four periods defined by events and interventions, on the basis of officially reported confirmed (58,084) and asymptomatic (591,346) cases. RESULTS: According to our model fitting, there were about 785,123 positive infections, of which about 57,585 positive infections were symptomatic infections. Our counterfactual assessment found that precise control by grid management was not so effective and that citywide static management was still needed. Universal and enforced control by citywide static management contained 87.65% and 96.29% of transmission opportunities, respectively. The number of daily new and cumulative infections could be significantly reduced if we implemented static management in advance. Moreover, if static management was implemented in the first 14 days of the epidemic, the number of daily new infections would be less than 10. CONCLUSIONS: The above research suggests that dynamic zeroing can only be achieved when strict prevention and control measures are implemented as early as possible. In addition, a lot of preparation is still needed if China wants to change its strategy in the future.