• Timothy E Sweeney, Oliver Liesenfeld, James Wacker, Yudong D He, David Rawling, Melissa Remmel, Sabrina Coyle, Uros Midic, Antigone Kotsaki, Aggeliki Kanavou, Konstantinos Leventogiannis, Ioanna Kontogeorgou, and Evangelos J Giamarellos-Bourboulis.
• Inflammatix, Burlingame, CA.
• Crit. Care Med. 2021 Feb 1; 49 (2): e170-e178.

ObjectivesComplex critical syndromes like sepsis and coronavirus disease 2019 may be composed of underling "endotypes," which may respond differently to treatment. The aim of this study was to test whether a previously defined bacterial sepsis endotypes classifier recapitulates the same clinical and immunological endotypes in coronavirus disease 2019.DesignProspective single-center observational cohort study.SettingPatients were enrolled in Athens, Greece, and blood was shipped to Inflammatix (Burlingame, CA) for analysis.PatientsAdult patients within 24 hours of hospital admission with coronavirus disease 2019 confirmed by polymerase chain reaction and chest radiography.InterventionsNone.Measurements And Main ResultsWe studied 97 patients with coronavirus disease 2019, of which 50 went on to severe respiratory failure (SRF) and 16 died. We applied a previously defined 33-messenger RNA classifier to assign endotype (Inflammopathic, Adaptive, or Coagulopathic) to each patient. We tested endotype status against other clinical parameters including laboratory values, severity scores, and outcomes. Patients were assigned as Inflammopathic (29%), Adaptive (44%), or Coagulopathic (27%), similar to our prior study in bacterial sepsis. Adaptive patients had lower rates of SRF and no deaths. Coagulopathic and Inflammopathic endotypes had 42% and 18% mortality rates, respectively. The Coagulopathic group showed highest d-dimers, and the Inflammopathic group showed highest C-reactive protein and interleukin-6 levels.ConclusionsOur predefined 33-messenger RNA endotypes classifier recapitulated immune phenotypes in viral sepsis (coronavirus disease 2019) despite its prior training and validation only in bacterial sepsis. Further work should focus on continued validation of the endotypes and their interaction with immunomodulatory therapy.Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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