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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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
Аннотация
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.