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Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial.
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- Additional Information
- Source:
Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 9801902 Publication Model: Electronic Cited Medium: Internet ISSN: 1466-609X (Electronic) Linking ISSN: 13648535 NLM ISO Abbreviation: Crit Care Subsets: MEDLINE
- Publication Information:
Publication: London, UK : BioMed Central Ltd
Original Publication: London : Current Science Ltd, c1997-
- Subject Terms:
- Abstract:
Background: Endotype classification may guide immunomodulatory management of patients with bacterial and viral sepsis. We aimed to identify immune endotypes and transitions associated with response to anakinra (human interleukin 1 receptor antagonist) in participants in the SAVE-MORE trial.
Methods: Adult patients hospitalized with radiological findings of PCR-confirmed severe pneumonia caused by SARS-CoV-2 and plasma-soluble urokinase plasminogen activator receptor levels of ≥ 6 ng/ml in the SAVE-MORE trial (NCT04680949) were characterized at baseline and days 4 and 7 of treatment using a previously defined 33-messenger RNA classifier to assign an immunological endotype in blood. Endpoints were changes in endotypes and progression to severe respiratory failure (SRF) associated with anakinra treatment.
Results: At baseline, 23.2% of 393 patients were designated as inflammopathic, 41.1% as adaptive, and 35.7% as coagulopathic. Only 23.9% were designated as the same endotype at days 4 and 7 compared to baseline, while all other patients transitioned between endotypes. Anakinra-treated patients were more likely to remain in the adaptive endotype during 7-day treatment (24.4% vs. 9.9%; p < 0.001). Anakinra also protected patients with coagulopathic endotype at day 7 against SRF compared to placebo (27.8% vs. 55.9%; p = 0.013).
Conclusion: We identify an association between endotypes defined using blood transcriptome and anakinra therapy for COVID-19 pneumonia, with anakinra-treated patients shifting toward endotypes associated with a better outcome, mainly the adaptive endotype. Trial registration ClinicalTrials.gov, NCT04680949, December 23, 2020.
(© 2024. The Author(s).)
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- Contributed Indexing:
Keywords: Anakinra; COVID-19; Endotypes; Viral sepsis
- Molecular Sequence:
ClinicalTrials.gov NCT04680949
- Accession Number:
0 (Interleukin 1 Receptor Antagonist Protein)
- Publication Date:
Date Created: 20240313 Date Completed: 20240314 Latest Revision: 20240405
- Publication Date:
20240405
- Accession Number:
PMC10935809
- Accession Number:
10.1186/s13054-024-04852-z
- Accession Number:
38475786
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