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. 2021 Feb 1;49(2):e170-e178.
doi: 10.1097/CCM.0000000000004786.

Validation of Inflammopathic, Adaptive, and Coagulopathic Sepsis Endotypes in Coronavirus Disease 2019

Timothy E Sweeney  1 , Oliver Liesenfeld  1 , James Wacker  1 , Yudong D He  1 , David Rawling  1 , Melissa Remmel  1 , Sabrina Coyle  1 , Uros Midic  1 , Antigone Kotsaki  2 , Aggeliki Kanavou  3 , Konstantinos Leventogiannis  2 , Ioanna Kontogeorgou  2 , Evangelos J Giamarellos-Bourboulis  2
Affiliations

Validation of Inflammopathic, Adaptive, and Coagulopathic Sepsis Endotypes in Coronavirus Disease 2019

Timothy E Sweeney et al. Crit Care Med. .

Abstract

Objectives: Complex 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.

Design: Prospective single-center observational cohort study.

Setting: Patients were enrolled in Athens, Greece, and blood was shipped to Inflammatix (Burlingame, CA) for analysis.

Patients: Adult patients within 24 hours of hospital admission with coronavirus disease 2019 confirmed by polymerase chain reaction and chest radiography.

Interventions: None.

Measurements and main results: We 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.

Conclusions: Our 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.

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Conflict of interest statement

Drs. Sweeney, Liesenfeld, Wacker, He, Rawling, and Midic received funding from Inflammatix. Drs. He and Kontogeorgou disclosed work for hire. Dr. Sweeney, Dr. Liesenfeld, Dr. Wacker, Dr. He, Dr. Rawling, Ms. Coyle, Dr. Midic are employees of, and stockholders in, Inflammatix, which has exclusive license to the patent covering the 33-messenger RNA set. Dr. Giamarellos-Bourboulis has received honoraria from AbbVie USA, Abbott CH, InflaRx GmbH, MSD Greece, XBiotech, and Angelini Italy; independent educational grants from AbbVie, Abbott, Astellas Pharma Europe, AxisShield, bioMérieux, InflaRx GmbH, and XBiotech; and funding from the FrameWork 7 program HemoSpec (granted to the National and Kapodistrian University of Athens), the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grant ImmunoSep (granted to the Hellenic Institute for the Study of Sepsis). The remaining authors have disclosed that they do not have any potential conflicts of interest.

Comment in

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