Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial.

Autor: Kyriazopoulou E; 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Hasin-Brumshtein Y; Inflammatix, Inc., Sunnyvale, CA, USA., Midic U; Inflammatix, Inc., Sunnyvale, CA, USA., Poulakou G; 3rd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Milionis H; 1st Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece., Metallidis S; 1st Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece., Astriti M; 1st Department of Internal Medicine, G. Gennimatas General Hospital of Athens, Athens, Greece., Fragkou A; Department of Internal Medicine, Elpis General Hospital, Athens, Greece., Rapti A; 2nd Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece., Taddei E; Dipartimento Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Gemelli IRCCS, Rome, Italy., Kalomenidis I; 1st Department of Critical Care and Pulmonary Medicine, Medical School, National and Kapodistrian University of Athens, Evangelismos General Hospital, Athens, Greece., Chrysos G; 2nd Department of Internal Medicine, Tzaneio General Hospital of Piraeus, Athens, Greece., Angheben A; Department of Infectious - Tropical Diseases and Microbiology, IRCSS Sacro Cuore Hospital, Negrar, Verona, Italy., Kainis I; 10th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases of Athens, Athens, Greece., Alexiou Z; 2nd Department of Internal Medicine, Thriasio General Hospital of Eleusis, Athens, Greece., Castelli F; Spedali Civili, Brescia ASST Spedali Civili Hospital, University of Brescia, Brescia, Italy., Serino FS; Department of Internal Medicine, Hospital of Jesolo, Jesolo, Italy., Bakakos P; 1st Department of Chest Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Nicastri E; Department of Internal Medicine, Spallanzani Institute of Rome, Rome, Italy., Tzavara V; 1st Department of Internal Medicine, Korgialeneion-Benakeion General Hospital, Athens, Greece., Ioannou S; Department of Therapeutics, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Dagna L; Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy., Dimakou K; 5th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases, Athens, Athens, Greece., Tzatzagou G; 1st Department of Internal Medicine, Papageorgiou General Hospital of Thessaloniki, Thessaloniki, Greece., Chini M; 3rd Department of Internal Medicine and Infectious Diseases Unit, Korgialeneion-Benakeion General Hospital, Athens, Greece., Bassetti M; Infectious Diseases Clinic, Ospedale Policlinico San Martino IRCCS and Department of Health Sciences, University of Genova, Genova, Italy., Kotsis V; 3rd Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece., Tsoukalas DG; 4th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece., Selmi C; Department of Biomedical Sciences, Humanitas University and IRCCS Humanitas Research Hospital, Milan, Italy., Konstantinou A; 1st Department of Internal Medicine, Asklepieio General Hospital of Voula, Voula, Greece., Samarkos M; 1st Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Doumas M; 2nd Department of Propedeutic Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece., Masgala A; 2nd Department of Internal Medicine, Konstantopouleio General Hospital, Athens, Greece., Pagkratis K; Department of Pulmonary Medicine, General Hospital of Kerkyra, Corfu, Greece., Argyraki A; Department of Internal Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece., Akinosoglou K; Department of Internal Medicine, University of Patras, Patras, Greece., Symbardi S; 1st Department of Internal Medicine, Thriasio General Hospital of Eleusis, Athens, Greece., Netea MG; Department of Internal Medicine and Center for Infectious Diseases, Radboud University, Nijmegen, The Netherlands.; Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany., Panagopoulos P; 2nd Department of Internal Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece., Dalekos GN; Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece., Liesenfeld O; Inflammatix, Inc., Sunnyvale, CA, USA., Sweeney TE; Inflammatix, Inc., Sunnyvale, CA, USA., Khatri P; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA., Giamarellos-Bourboulis EJ; 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece. egiamarel@med.uoa.gr.; 4th Department of Internal Medicine, ATTIKON University Hospital, 1 Rimini Street, 124 62, Athens, Greece. egiamarel@med.uoa.gr.
Jazyk: angličtina
Zdroj: Critical care (London, England) [Crit Care] 2024 Mar 12; Vol. 28 (1), pp. 73. Date of Electronic Publication: 2024 Mar 12.
DOI: 10.1186/s13054-024-04852-z
Abstrakt: 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).)
Databáze: MEDLINE
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