Background Pneumonia is a common cause of morbidity and mortality, with severe cases often progressing to complications such as sepsis and respiratory failure. Early diagnosis and intervention are crucial for improving outcomes. MicroRNAs (miRNAs) have been identified as potential biomarkers for various diseases, including pneumonia. This study aimed to evaluate the potential role of miR-6822-3p as a diagnostic and prognostic biomarker in severe pneumonia and to explore its underlying mechanisms. Methods The GSE153131 dataset from the GEO database was analyzed to identify differentially expressed miRNAs. Serum samples from 70 mild pneumonia patients, 70 severe pneumonia patients, and 70 healthy controls were used to validate miR-6822-3p expression. In vitro experiments using A549 and THP-1 cells were conducted to investigate the role of miR-6822-3p in inflammation and pyroptosis. Results miR-6822-3p was significantly upregulated in severe pneumonia patients and showed potential as a diagnostic biomarker. In vitro studies revealed that miR-6822-3p promoted inflammation and pyroptosis. High miR-6822-3p expression was associated with poorer clinical outcomes, including lower 28-day survival rates. Conclusions miR-6822-3p may be a potential diagnostic and prognostic biomarker for severe pneumonia. Further studies are needed to validate its clinical utility and explore its therapeutic potential.
Objective: To determine whether ivermectin improves outcomes for critically and noncritically ill hospitalized patients with COVID-19.Design: An ongoing international, multifactorial, adaptive platform, randomized, controlled trial.Setting: Hospitals in Pakistan, India, and Ireland between June 11, 2021, and September 9, 2022.Patients: Critically and noncritically ill patients.Interventions: Randomized to ivermectin or no ivermectin (control).Measurements and Main Results: The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors. Analyses used a Bayesian cumulative logistic model. Enrollment was closed for operational futility, following external evidence suggesting no benefit with ivermectin in nonhospitalized patients with COVID-19. Among 61 critically ill patients, the median number of organ support-free days was -1, indicating death was the most common vital outcome (interquartile range [IQR], -1 to 17), for the ivermectin group and -1 (IQR, -1 to 17.25) for the control group (adjusted proportional odds ratio [OR], 0.94; 95% credible interval [CrI], 0.40-2.07) and the posterior probability of superiority to control was 44.2%. Among 89 noncritically ill patients, the median number of organ support-free days was 22 (IQR, 18.5-22) for ivermectin and 22 (IQR, 16-22) for control (adjusted proportional OR, 1.04; 95% CrI, 0.48-2.34) and the posterior probability of superiority was 53.7%. Among critically ill patients, hospital survival was 35.1% (13/37) for ivermectin and 37.5% (9/24) for control (adjusted OR, 1.00; 95% CrI, 0.39-2.32), posterior probability of superiority was 50.0%. Among noncritically ill patients, hospital survival was 84.1% (37/44) for ivermectin and 77.8% (35/45) for control (adjusted OR, 1.16; 95% CrI, 0.5-3.07), posterior probability of superiority was 63.3%.Conclusions: For critically and noncritically ill hospitalized patients with COVID-19, ivermectin was unlikely to improve the primary composite outcome of organ support-free days and hospital survival.
