Validation of Inflammopathic, Adaptive, and Coagulopathic Sepsis Endotypes in Coronavirus Disease 2019.
Journal
Critical care medicine
ISSN: 1530-0293
Titre abrégé: Crit Care Med
Pays: United States
ID NLM: 0355501
Informations de publication
Date de publication:
01 02 2021
01 02 2021
Historique:
pubmed:
18
11
2020
medline:
26
1
2021
entrez:
17
11
2020
Statut:
ppublish
Résumé
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. Prospective single-center observational cohort study. Patients were enrolled in Athens, Greece, and blood was shipped to Inflammatix (Burlingame, CA) for analysis. Adult patients within 24 hours of hospital admission with coronavirus disease 2019 confirmed by polymerase chain reaction and chest radiography. None. 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. 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.
Identifiants
pubmed: 33201004
pii: 00003246-202102000-00036
doi: 10.1097/CCM.0000000000004786
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e170-e178Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Déclaration de conflit d'intérêts
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.
Références
Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016; 315:801–810
Opal SM, Dellinger RP, Vincent JL, et al. The next generation of sepsis clinical trial designs: What is next after the demise of recombinant human activated protein C?*. Crit Care Med. 2014; 42:1714–1721
Prescott HC, Calfee CS, Thompson BT, et al. Toward smarter lumping and smarter splitting: Rethinking strategies for sepsis and acute respiratory distress syndrome clinical trial design. Am J Respir Crit Care Med. 2016; 194:147–155
Berlin DA, Gulick RM, Martinez FJ. Severe Covid-19. N Engl J Med. 2020 May 15. [online ahead of print]
Xiong M, Liang X, Wei YD. Changes in blood coagulation in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis. Br J Haematol. 2020; 189:1050–1052
Han H, Yang L, Liu R, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020; 58:1116–1120
Tang N, Bai H, Chen X, et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020; 18:1094–1099
The Lancet Haematology. COVID-19 coagulopathy: An evolving story. Lancet Haematol. 2020; 7:e425
Antwi-Amoabeng D, Kanji Z, Ford B, et al. Clinical outcomes in COVID-19 patients treated with tocilizumab: An individual patient data systematic review. J Med Virol. 2020; 92:2516–2522
Dimopoulos G, de Mast Q, Markou N, et al. Favorable anakinra responses in severe Covid-19 patients with secondary hemophagocytic lymphohistiocytosis. Cell Host Microbe. 2020; 28:117–123.e1
Giamarellos-Bourboulis EJ, Netea MG, Rovina N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020; 27:992–1000.e3
Li H, Liu L, Zhang D, et al. SARS-CoV-2 and viral sepsis: Observations and hypotheses. Lancet. 2020; 395:1517–1520
Sweeney TE, Azad TD, Donato M, et al. Unsupervised analysis of transcriptomics in bacterial sepsis across multiple datasets reveals three robust clusters. Crit Care Med. 2018; 46:915–925
Mayhew MB, Buturovic L, Luethy R, et al. A generalizable 29-mRNA neural-network classifier for acute bacterial and viral infections. Nat Commun. 2020; 11:1177
Toh CH, Hoots WK; SSC on Disseminated Intravascular Coagulation of the ISTH. The scoring system of the Scientific and Standardisation Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: A 5-year overview. J Thromb Haemost. 2007; 5:604–606
Jose RJ, Manuel A. COVID-19 cytokine storm: The interplay between inflammation and coagulation. Lancet Respir Med. 2020; 8:e46–e47
Mehta P, McAuley DF, Brown M, et al.; HLH Across Speciality Collaboration, UK. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet. 2020; 395:1033–1034
Wong HR, Cvijanovich N, Lin R, et al. Identification of pediatric septic shock subclasses based on genome-wide expression profiling. BMC Med. 2009; 7:34
Wong HR, Sweeney TE, Hart KW, et al. Pediatric sepsis endotypes among adults with sepsis. Crit Care Med. 2017; 45:e1289–e1291
Burnham KL, Davenport EE, Radhakrishnan J, et al. Shared and distinct aspects of the sepsis transcriptomic response to fecal peritonitis and pneumonia. Am J Respir Crit Care Med. 2017; 196:328–339
Scicluna BP, van Vught LA, Zwinderman AH, et al.; MARS Consortium. Classification of patients with sepsis according to blood genomic endotype: A prospective cohort study. Lancet Respir Med. 2017; 5:816–826
Calfee CS, Delucchi K, Parsons PE, et al.; NHLBI ARDS Network. Subphenotypes in acute respiratory distress syndrome: Latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014; 2:611–620
Wong HR, Cvijanovich NZ, Anas N, et al. Developing a clinically feasible personalized medicine approach to pediatric septic shock. Am J Respir Crit Care Med. 2015; 191:309–315
Mathew D, Giles JR, Baxter AE, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science. 2020; 369:eabc8511
Arunachalam PS, Wimmers F, Mok CKP, et al. Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans. Science. 2020; 369:1210–1220
Laing AG, Lorenc A, Del Molino Del Barrio I, et al. A dynamic COVID-19 immune signature includes associations with poor prognosis. Nat Med. 2020; 26:1623–1635
Horby P, Lim WS, Emberson JR, et al.; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19 - preliminary report. N Engl J Med. 2020 Jul 17. [online ahead of print]