Immunomodulation for acute respiratory distress syndrome: insights from proteomics in COVID-19
CHEST Critical Care, 2025
Rademaker E., Haitsma Mulier J., Drylewicz J., Delemarre E., Slim M., Juffermans N., Pickkers P., Bonten M., Cremer O., Derde L.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Respiratory Diseases Infectious Diseases Immunotherapy | Pathophysiology | Plasma | O Olink Target 96 |
Abstract
Background
The success of targeted immunomodulation in COVID-19 underscores its potential for acute respiratory distress syndrome (ARDS) from other causes. However, it is important to understand both its targeted and broader impacts on the inflammatory host response. To guide future ARDS studies, we explored this in COVID-19 patients, using targeted proteomics.
Research Question
How do different immune modulators affect the immune profiles of critically-ill patients with COVID-19-related ARDS?
Study Design and Methods
In this multicenter cohort study, we utilized two Dutch biorepositories to compare COVID-19 patients with acute respiratory failure treated with: no immunotherapy (n=18), corticosteroids (n=21), anakinra plus corticosteroids (n=9), and tocilizumab plus corticosteroids (n=22). Plasma proteins related to inflammation and cardiovascular injury were measured using proximity extension assays on days 0 (T0), 2-4 (T3) and 6-8 (T7) after treatment initiation.
Results
We observed lower expression of inflammatory biomarkers immediately following tocilizumab administration, and from T3 onwards after anakinra administration. Following corticosteroids alone, fewer inflammatory biomarkers were suppressed, and only at T3. Multivariate analyses at T3 identified TRAIL, IL-1RL2 and TNF-β as markedly increased, and SRC and STK4 as decreased, solely after tocilizumab. At T7, DECR1, SLAMF7, SRC, and STK4, had lower concentrations in patients treated with tocilizumab or anakinra, whereas IFN-gamma, CXCL-9, and CCL-19 were decreased only after anakinra.