Prof. Dr. Mihai Netea
Life & Medical Sciences Institute (LIMES)
mnetea@uni-bonn.de View member: Prof. Dr. Mihai Netea
Critical care (London, England)
Authors: Evdoxia Kyriazopoulou, Yehudit Hasin-Brumshtein, Uros Midic, Garyfallia Poulakou, Haralampos Milionis, Simeon Metallidis, Myrto Astriti, Archontoula Fragkou, Aggeliki Rapti, Eleonora Taddei, Ioannis Kalomenidis, Georgios Chrysos, Andrea Angheben, Ilias Kainis, Zoi Alexiou, Francesco Castelli, Francesco Saverio Serino, Petros Bakakos, Emanuele Nicastri, Vasiliki Tzavara, Sofia Ioannou, Lorenzo Dagna, Katerina Dimakou, Glykeria Tzatzagou, Maria Chini, Matteo Bassetti, Vasileios Kotsis, Dionysios G Tsoukalas, Carlo Selmi, Alexandra Konstantinou, Michael Samarkos, Michael Doumas, Aikaterini Masgala, Konstantinos Pagkratis, Aikaterini Argyraki, Karolina Akinosoglou, Styliani Symbardi, Mihai G Netea, Periklis Panagopoulos, George N Dalekos, Oliver Liesenfeld, Timothy E Sweeney, Purvesh Khatri, Evangelos J Giamarellos-Bourboulis
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).
PMID: 38475786