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Late Breaking Abstract - Enhanced immune activation pathways enriched in patients =70 years with severe COVID-19

Luke O'Neill, Charlotte Summers, Gift Nyamundanda, Johannes Freudenberg, Anubha Gupta, Julia Smith, Sumanta Mukherjee, Jessica Neisen
European Respiratory Journal 2021 58: PA3782; DOI: 10.1183/13993003.congress-2021.PA3782
Luke O'Neill
1Trinity Biomedical Sciences Institute, Dublin, Ireland
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  • For correspondence: LAONEILL@tcd.ie
Charlotte Summers
2University of Cambridge, Cambridge, United Kingdom
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Gift Nyamundanda
3GlaxoSmithKline, Stevenage, Hertfordshire, United Kingdom
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Johannes Freudenberg
4GlaxoSmithKline, Collegeville, PA, United States of America
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Anubha Gupta
3GlaxoSmithKline, Stevenage, Hertfordshire, United Kingdom
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Julia Smith
3GlaxoSmithKline, Stevenage, Hertfordshire, United Kingdom
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Sumanta Mukherjee
5GlaxoSmithKline, Collegeville, United States of America
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Jessica Neisen
3GlaxoSmithKline, Stevenage, Hertfordshire, United Kingdom
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Abstract

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.

  • Covid-19
  • Biomarkers
  • Inflammation

Footnotes

Cite 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).

  • Copyright ©the authors 2021
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Late Breaking Abstract - Enhanced immune activation pathways enriched in patients =70 years with severe COVID-19
Luke O'Neill, Charlotte Summers, Gift Nyamundanda, Johannes Freudenberg, Anubha Gupta, Julia Smith, Sumanta Mukherjee, Jessica Neisen
European Respiratory Journal Sep 2021, 58 (suppl 65) PA3782; DOI: 10.1183/13993003.congress-2021.PA3782

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Late Breaking Abstract - Enhanced immune activation pathways enriched in patients =70 years with severe COVID-19
Luke O'Neill, Charlotte Summers, Gift Nyamundanda, Johannes Freudenberg, Anubha Gupta, Julia Smith, Sumanta Mukherjee, Jessica Neisen
European Respiratory Journal Sep 2021, 58 (suppl 65) PA3782; DOI: 10.1183/13993003.congress-2021.PA3782
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