Intensive Care Medicine Experimental (Jun 2025)
29-mRNA host response signatures for classification of bacterial infection, viral infection and disease progression in COVID-19 pneumonia: a post hoc analysis of the SAVE-MORE randomized clinical trial
- Evdoxia Kyriazopoulou,
- Antigone Kotsaki,
- Asimina Safarika,
- Garyfallia Poulakou,
- Haralampos Milionis,
- Simeon Metallidis,
- Georgios Adamis,
- Archontoula Fragkou,
- Aggeliki Rapti,
- Pierluigi Del Vecchio,
- Ioannis Kalomenidis,
- Danae Kitzoglou,
- Andrea Angheben,
- Ilias Kainis,
- Konstantina Iliopoulou,
- Francesco Saverio Serino,
- Petros Bakakos,
- Vassiliki Tzavara,
- Sofia Ioannou,
- Lorenzo Dagna,
- Katerina Dimakou,
- Glykeria Tzatzagou,
- Maria Chini,
- Matteo Bassetti,
- Vasileios Kotsis,
- George Tsoukalas,
- Carlo Selmi,
- Sofia Nikolakopoulou,
- Michael Samarkos,
- Michael Doumas,
- Aikaterini Masgala,
- Ilias Papanikolaou,
- Aikaterini Argyraki,
- Karolina Akinosoglou,
- Styliani Symbardi,
- Periklis Panagopoulos,
- George N. Dalekos,
- Oliver Liesenfeld,
- Timothy E. Sweeney,
- Purvesh Khatri,
- Evangelos J. Giamarellos-Bourboulis
Affiliations
- Evdoxia Kyriazopoulou
- 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens
- Antigone Kotsaki
- 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens
- Asimina Safarika
- 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens
- Garyfallia Poulakou
- 3rd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens
- Haralampos Milionis
- 1st Department of Internal Medicine, Medical School, University of Ioannina
- Simeon Metallidis
- 1st Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki
- Georgios Adamis
- 1st Department of Internal Medicine, G. Gennimatas General Hospital of Athens
- Archontoula Fragkou
- Department of Internal Medicine, Elpis General Hospital
- Aggeliki Rapti
- 2nd Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases
- Pierluigi Del Vecchio
- Unità Operativa Complessa (UOC) Malattie Infettive-Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Gemelli IRCCS
- Ioannis Kalomenidis
- 1st Department of Critical Care and Pulmonary Medicine, Medical School, Evangelismos General Hospital, National and Kapodistrian University of Athens
- Danae Kitzoglou
- 10th Department of Internal Medicine, Tzaneio General Hospital of Piraeus
- Andrea Angheben
- Department of Infectious–Tropical Diseases and Microbiology, IRCSS Sacro Cuore Hospital
- Ilias Kainis
- 10th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases of Athens
- Konstantina Iliopoulou
- 2nd Department of Internal Medicine, Thriasio General Hospital of Eleusis
- Francesco Saverio Serino
- Department of Internal Medicine, Hospital of Jesolo
- Petros Bakakos
- 1st Department of Chest Medicine, Medical School, National and Kapodistrian University of Athens
- Vassiliki Tzavara
- 1st Department of Internal Medicine, Korgialeneion-Benakeion General Hospital
- Sofia Ioannou
- Department of Therapeutics, Medical School, National and Kapodistrian University of Athens
- Lorenzo Dagna
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele & Vita-Salute San Raffaele University
- Katerina Dimakou
- 5th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases
- Glykeria Tzatzagou
- 1st Department of Internal Medicine, Papageorgiou General Hospital of Thessaloniki
- Maria Chini
- 3rd Department of Internal Medicine and Infectious Diseases Unit, Korgialeneion-Benakeion General Hospital
- Matteo Bassetti
- Infectious Diseases Clinic, Ospedale Policlinico San Martino IRCCS and Department of Health Sciences, University of Genova
- Vasileios Kotsis
- 3rd Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki
- George Tsoukalas
- 4th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases
- Carlo Selmi
- Humanitas Research Hospital
- Sofia Nikolakopoulou
- Covid-19 Department, Asklipieio General Hospital of Voula
- Michael Samarkos
- 1st Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens
- Michael Doumas
- 2nd Department of Propedeutic Medicine, Medical School, Aristotle University of Thessaloniki
- Aikaterini Masgala
- 2nd Department of Internal Medicine, Konstantopouleio General Hospital
- Ilias Papanikolaou
- Department of Pulmonary Medicine, General Hospital of Kerkyra
- Aikaterini Argyraki
- Department of Internal Medicine, Sotiria General Hospital of Chest Diseases
- Karolina Akinosoglou
- Department of Internal Medicine, University of Patras
- Styliani Symbardi
- 1st Department of Internal Medicine, Thriasio General Hospital of Eleusis
- Periklis Panagopoulos
- 2nd Department of Internal Medicine, Medical School, Democritus University of Thrace
- George N. Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa
- Oliver Liesenfeld
- Inflammatix, Inc.
- Timothy E. Sweeney
- Inflammatix, Inc.
- Purvesh Khatri
- Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University
- Evangelos J. Giamarellos-Bourboulis
- 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens
- DOI
- https://doi.org/10.1186/s40635-025-00777-1
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 10
Abstract
Abstract Background Biomarkers based on host response signatures are currently under development for the critically ill. We applied a 29-mRNA classifier for the diagnosis and prognosis of suspected acute infection and sepsis (TriVerity™, Inflammatix Inc.) in patients hospitalized with COVID-19. Methods We applied three scores from locked classifiers (IMX-BVN-4 and IMX-SEV-4) from the 29-mRNA TriVerity™ blood test in participants of the SAVE-MORE randomized clinical trial (ClinicalTrials.gov NCT04680949) at baseline and days 4 and 7 of treatment, to classify bacterial infection, viral infection and decompensation. Participants were adults hospitalized with confirmed COVID-19 pneumonia and plasma soluble urokinase plasminogen activator receptor (suPAR) levels of ≥ 6 ng/ml, randomized to placebo or anakinra treatment. Results A total of 471 patients were studied. At baseline nearly 90% had a Very Low or Low IMX-BVN-4 Bacterial Score and Moderate, High or Very High IMX-BVN-4 Viral Score. Anakinra treatment had an effect on the expression of genes indicating IMX-SEV-4 High or Very High scores after a 7 day treatment compared to baseline (12.9% of anakinra-treated patients continued being classified as high severity vs 20.4% of placebo-treated patients, p 0.046). Conclusions The classifiers were well tested in COVID-19 pneumonia and may become a useful tool for hospitalized patients.
Keywords
