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

• Published in: Critical care (London, England) England), 2024-03, Vol.28 (1), p.73-73, Article 73
• Main Authors: Kyriazopoulou, Evdoxia, Hasin-Brumshtein, Yehudit, Midic, Uros, Poulakou, Garyfallia, Milionis, Haralampos, Metallidis, Simeon, Astriti, Myrto, Fragkou, Archontoula, Rapti, Aggeliki, Taddei, Eleonora, Kalomenidis, Ioannis, Chrysos, Georgios, Angheben, Andrea, Kainis, Ilias, Alexiou, Zoi, Castelli, Francesco, Serino, Francesco Saverio, Bakakos, Petros, Nicastri, Emanuele, Tzavara, Vasiliki, Ioannou, Sofia, Dagna, Lorenzo, Dimakou, Katerina, Tzatzagou, Glykeria, Chini, Maria, Bassetti, Matteo, Kotsis, Vasileios, Tsoukalas, Dionysios G, Selmi, Carlo, Konstantinou, Alexandra, Samarkos, Michael, Doumas, Michael, Masgala, Aikaterini, Pagkratis, Konstantinos, Argyraki, Aikaterini, Akinosoglou, Karolina, Symbardi, Styliani, Netea, Mihai G, Panagopoulos, Periklis, Dalekos, George N, Liesenfeld, Oliver, Sweeney, Timothy E, Khatri, Purvesh, Giamarellos-Bourboulis, Evangelos J
• Format: Article
• Language: English
• Subjects: Adult; Bacterial pneumonia; Blood; Body mass index; Care and treatment; Clinical trials; Confounding (Statistics); Coronaviruses; COVID-19; Cytokines; Disease transmission; FDA approval; Gene expression; Hospital patients; Humans; Interleukin 1 Receptor Antagonist Protein - therapeutic use; Interleukins; Medical research; Medicine, Experimental; Pandemics; Patient outcomes; Patients; Pneumonia; Pneumonia - drug therapy; Regression analysis; RNA; SARS-CoV-2; Sepsis; Statistical analysis; Task forces; Transcriptome; Variables; Ventilators
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1366-609X
• DOI: 10.1186/s13054-024-04852-z

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. 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. 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