Clinical Phenotyping for Prognosis and Immunotherapy Guidance in Bacterial Sepsis and COVID-19

Eleni Karakike, MD, PhD; Simeon Metallidis, MD, PhD; Garyfallia Poulakou, MD, PhD; Maria Kosmidou, MD, PhD; Nikolaos K. Gatselis, MD, PhD; Vasileios Petrakis, MD, PhD; Nikoletta Rovina, MD, PhD; Eleni Gkeka, MD, PhD; Styliani Sympardi, MD, PhD; Ilias Papanikolaou, MD, PhD; Ioannis Koutsodimitropoulos, MD, PhD; Vasiliki Tzavara, MD, PhD; Georgios Adamis, MD, PhD; Konstantinos Tsiakos, MD; Vasilios Koulouras, MD, PhD; Eleni Mouloudi, MD, PhD; Eleni Antoniadou, MD, PhD; Gykeria Vlachogianni, MD, PhD; Souzana Anisoglou, MD, PhD; Nikolaos Markou, MD, PhD; Antonia Koutsoukou, MD, PhD; Periklis Panagopoulos, MD, PhD; Haralampos Milionis, MD, PhD; George N. Dalekos, MD, PhD; Miltiades Kyprianou; Evangelos J. Giamarellos-Bourboulis, MD, PhD

doi:10.1097/CCE.0000000000001153

Critical Care Explorations (Sep 2024)

Clinical Phenotyping for Prognosis and Immunotherapy Guidance in Bacterial Sepsis and COVID-19

Eleni Karakike, MD, PhD,
Simeon Metallidis, MD, PhD,
Garyfallia Poulakou, MD, PhD,
Maria Kosmidou, MD, PhD,
Nikolaos K. Gatselis, MD, PhD,
Vasileios Petrakis, MD, PhD,
Nikoletta Rovina, MD, PhD,
Eleni Gkeka, MD, PhD,
Styliani Sympardi, MD, PhD,
Ilias Papanikolaou, MD, PhD,
Ioannis Koutsodimitropoulos, MD, PhD,
Vasiliki Tzavara, MD, PhD,
Georgios Adamis, MD, PhD,
Konstantinos Tsiakos, MD,
Vasilios Koulouras, MD, PhD,
Eleni Mouloudi, MD, PhD,
Eleni Antoniadou, MD, PhD,
Gykeria Vlachogianni, MD, PhD,
Souzana Anisoglou, MD, PhD,
Nikolaos Markou, MD, PhD,
Antonia Koutsoukou, MD, PhD,
Periklis Panagopoulos, MD, PhD,
Haralampos Milionis, MD, PhD,
George N. Dalekos, MD, PhD,
Miltiades Kyprianou,
Evangelos J. Giamarellos-Bourboulis, MD, PhD

Affiliations

Eleni Karakike, MD, PhD: 1 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Simeon Metallidis, MD, PhD: 2 1st Department of Internal Medicine, Aristotle University of Thessaloniki, Medical School, Thessaloniki, Greece.
Garyfallia Poulakou, MD, PhD: 3 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Maria Kosmidou, MD, PhD: 4 1st Department of Internal Medicine, University General Hospital of Ioannina, Ioannina, Greece.
Nikolaos K. Gatselis, MD, PhD: 5 Department of Internal Medicine, Larissa University General Hospital, University of Thessaly, Larissa, Greece.
Vasileios Petrakis, MD, PhD: 6 2nd Department of Internal Medicine, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
Nikoletta Rovina, MD, PhD: 7 1st Department of Pulmonary Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Eleni Gkeka, MD, PhD: 8 Intensive Care Unit, AHEPA University General Hospital of Thessaloniki, Thessaloniki, Greece.
Styliani Sympardi, MD, PhD: 9 1st Department of Internal Medicine, Elefsis General Hospital Thriassio, Elefsis, Greece.
Ilias Papanikolaou, MD, PhD: 10 Department of Pulmonary Medicine, Kerkyra General Hospital, Corfu, Greece.
Ioannis Koutsodimitropoulos, MD, PhD: 11 Intensive Care Unit of Latseion Burn Center, Elefsis General Hospital Thriassio, Elefsis, Greece.
Vasiliki Tzavara, MD, PhD: 12 1st Department of Internal Medicine, “Korgialeneio-Benakeio” Athens General Hospital, Athens, Greece.
Georgios Adamis, MD, PhD: 13 1st Department of Internal Medicine, “G.Gennimatas” Athens General Hospital, Athens, Greece.
Konstantinos Tsiakos, MD: 3 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Vasilios Koulouras, MD, PhD: 14 Department of Critical Care Medicine, University General Hospital of Ioannina, Ioannina, Greece.
Eleni Mouloudi, MD, PhD: 15 Intensive Care Unit, “Ippokrateion” General Hospital of Thessaloniki, Thessaloniki, Greece.
Eleni Antoniadou, MD, PhD: 16 Intensive Care Unit, “G.Gennimatas” General Hospital of Thessaloniki, Thessaloniki, Greece.
Gykeria Vlachogianni, MD, PhD: 17 Intensive Care Unit, “Aghios Dimitrios” General Hospital of Thessaloniki, Thessaloniki, Greece.
Souzana Anisoglou, MD, PhD: 18 Intensive Care Unit, “Theageneion” General Hospital of Thessaloniki, Thessaloniki, Greece.
Nikolaos Markou, MD, PhD: 11 Intensive Care Unit of Latseion Burn Center, Elefsis General Hospital Thriassio, Elefsis, Greece.
Antonia Koutsoukou, MD, PhD: 7 1st Department of Pulmonary Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Periklis Panagopoulos, MD, PhD: 6 2nd Department of Internal Medicine, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
Haralampos Milionis, MD, PhD: 4 1st Department of Internal Medicine, University General Hospital of Ioannina, Ioannina, Greece.
George N. Dalekos, MD, PhD: 5 Department of Internal Medicine, Larissa University General Hospital, University of Thessaly, Larissa, Greece.
Miltiades Kyprianou: 19 Hellenic Institute for the Study of Sepsis, Athens, Greece.
Evangelos J. Giamarellos-Bourboulis, MD, PhD: 1 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

DOI: https://doi.org/10.1097/CCE.0000000000001153
Journal volume & issue: Vol. 6, no. 9
p. e1153

Abstract

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OBJECTIVES:. It is suggested that sepsis may be classified into four clinical phenotypes, using an algorithm employing 29 admission parameters. We applied a simplified phenotyping algorithm among patients with bacterial sepsis and severe COVID-19 and assessed characteristics and outcomes of the derived phenotypes. DESIGN:. Retrospective analysis of data from prospective clinical studies. SETTING:. Greek ICUs and Internal Medicine departments. PATIENTS AND INTERVENTIONS:. We analyzed 1498 patients, 620 with bacterial sepsis and 878 with severe COVID-19. We implemented a six-parameter algorithm (creatinine, lactate, aspartate transaminase, bilirubin, C-reactive protein, and international normalized ratio) to classify patients with bacterial sepsis intro previously defined phenotypes. Patients with severe COVID-19, included in two open-label immunotherapy trials were subsequently classified. Heterogeneity of treatment effect of anakinra was assessed. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS:. The algorithm validated the presence of the four phenotypes across the cohort of bacterial sepsis and the individual studies included in this cohort. Phenotype α represented younger patients with low risk of death, β was associated with high comorbidity burden, and δ with the highest mortality. Phenotype assignment was independently associated with outcome, even after adjustment for Charlson Comorbidity Index. Phenotype distribution and outcomes in severe COVID-19 followed a similar pattern. CONCLUSIONS:. A simplified algorithm successfully identified previously derived phenotypes of bacterial sepsis, which were predictive of outcome. This classification may apply to patients with severe COVID-19 with prognostic implications.

Published in Critical Care Explorations

ISSN: 2639-8028 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Medical emergencies. Critical care. Intensive care. First aid
Website: https://journals.lww.com/ccejournal/pages/default.aspx

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