TY - JOUR T1 - Late Breaking Abstract - Enhanced immune activation pathways enriched in patients =70 years with severe COVID-19 JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2021.PA3782 VL - 58 IS - suppl 65 SP - PA3782 AU - Luke O'Neill AU - Charlotte Summers AU - Gift Nyamundanda AU - Johannes Freudenberg AU - Anubha Gupta AU - Julia Smith AU - Sumanta Mukherjee AU - Jessica Neisen Y1 - 2021/09/05 UR - http://erj.ersjournals.com/content/58/suppl_65/PA3782.abstract N2 - Introduction: Dysregulated immune responses are a key feature of severe coronavirus disease 2019 (COVID-19) pathophysiology. Despite common symptoms there is disparity in patients’ recovery, driving research into targeted therapies.Aim: To characterize the biological mechanisms in COVID-19 recovery.Methods: Serum proteomics (Olink platform) was carried out on 350 patients within the placebo and otilimab arms of OSCAR Part 1 (Otilimab in Severe COVID-19-Related Disease; NCT04376684). Patients were stratified by clinical response or mortality at Day 28, baseline severity, age (70y) and comorbidity status. Differentially expressed proteins (DEPs) at baseline were characterized.Results: Each stratification revealed 300+ DEPs that were assessed for enrichment of biological pathways. The tumor necrosis factor receptor 2 non-canonical NF-κB pathway was enriched in all groups, as was a cluster of pathways associated with dysfunctional protein metabolism and post‑translational modification. The size of this latter cluster was highly variable between groups. A distinct cluster of pathways linked to programmed cell death was associated with the fatal and ≥70y groups, but not observed in the severity or response analyses. Unique to the ≥70y group was a cluster of fibroblast growth factor-related and phospholipase C signaling pathways, potentially indicative of enhanced immune cell activation.Conclusion: These analyses reinforce the need for personalized treatment of severe COVID-19 and build rationale for poor outcomes in specific patient groups including older age.Funded by GSK: medical writing support provided by Fishawack Indicia Ltd, funded by GSK.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA3782.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -