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Introduction <p>The clinical presentation of critically ill patients with coronavirus disease 2019 (COVID-19) has evolved significantly with the emergence of the Omicron variant. Current intensive care unit (ICU) admissions involve patients with diverse comorbidities and immune statuses, highlighting the need to redefine homogeneous phenotypic subgroups within this population. This study aimed to characterize distinct clinical phenotypes among critically ill patients with COVID-19 and acute respiratory failure.</p> Methods <p>This multicenter prospective substudy of the SEVARVIR cohort included adult patients from 39 French ICUs between December 2021 and October 2024 with acute respiratory failure and infected with the Omicron variant. Clustering analysis was conducted using Kohonen’s self-organizing maps (SOMs) and validated with ClinTrajan, two unsupervised clustering methods, to identify homogeneous patient phenotypes.</p> Results <p>During the study period, 777 patients with Omicron infection were included, and 7 distinct clinical clusters were identified. Clusters 1 and 2 included patients with metabolic and cardiovascular comorbidities. Cluster 3 featured younger, mildly ill patients with isolated chronic respiratory failure, while cluster 4 comprised older male patients with isolated respiratory failure. Cluster 5 included patients with isolated hematologic malignancies, cluster 6 patients with multiorgan failure, and cluster 7 organ transplant recipients, with high severity scores and impaired renal function. ICU management varied substantially across clusters. Patients in clusters 5 and 7 had the highest requirements for organ support, with frequent use of invasive mechanical ventilation, vasopressors (cluster 6), and renal replacement therapy (cluster 7). Dexamethasone and tocilizumab were most commonly prescribed in cluster 4 (91.3% and 30.2%, respectively). Mortality at day 28 varied significantly across clusters, ranging from 13.1% in cluster 3 to 41.1% in cluster 6.</p> Conclusions <p>This clustering analysis highlights, for the first time, the clinical heterogeneity of critically ill patients infected with Omicron, identifying seven distinct clusters with varying clinical presentations, management strategies and outcomes. These findings underscore the relevance of a phenotype-driven approach to support personalized treatment strategies and guide future clinical trials.</p> Trial Registration <p>Clinicaltrials.gov, NCT05162508.</p> <p>A Graphical Abstract is available for this article.</p> Graphical Abstract <p></p>

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Clinical Phenotypes of Critically Ill Patients with COVID-19 Infected with Omicron: A Nationwide Prospective Cohort Study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月6日

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  • Etienne Audureau,
  • Pierre Bay,
  • Sébastien Préau,
  • Raphaël Favory,
  • Aurélie Guigon,
  • Nicholas Heming,
  • Elyanne Gault,
  • Tài Pham,
  • Amal Chaghouri,
  • Matthieu Turpin,
  • Laurence Morand-Joubert,
  • Sébastien Jochmans,
  • Aurélia Pitsch,
  • Sylvie Meireles,
  • Damien Contou,
  • Amandine Henry,
  • Damien Roux,
  • Quentin Le Hingrat,
  • Antoine Kimmoun,
  • Cédric Hartard,
  • Frédéric Pène,
  • Anne-Sophie L’Honneur,
  • Antoine Guillon,
  • Lynda Handala,
  • Fabienne Tamion,
  • Alice Moisan,
  • Thomas Daix,
  • Sébastien Hantz,
  • Flora Delamaire,
  • Vincent Thibault,
  • Cédric Darreau,
  • Jean Thomin,
  • Jean-Michel Pawlotsky,
  • Slim Fourati,
  • Nicolas de Prost,
  • Keyvan Razazi,
  • Armand Mekontso Dessap,
  • Raphaël Bellaïche,
  • Lucile Picard,
  • Christophe Rodriguez,
  • Frédéric Pene,
  • Adrien Joseph,
  • Elie Azoulay,
  • Marie-Laure Chaix,
  • Charles-Edouard Luyt,
  • David Levy,
  • Julien Mayaux,
  • Stéphane Marot,
  • Djeneba Bocar Fofana,
  • Maxime Gasperment,
  • Tomas Urbina,
  • Hafid Ait Oufella,
  • Eric Maury,
  • Jean-François Timsit,
  • Diane Descamps,
  • Guillaume Voiriot,
  • Nina De Montmollin,
  • Mathieu Turpin,
  • Bruno Mégarbane,
  • Stéphane Gaudry,
  • Ségolène Brichler,
  • Louis Mourier,
  • Fabrice Uhel,
  • Tài Olivier Pham,
  • Anne-Marie Roque-Alfonso,
  • Djillali Annane,
  • Antoine Vieillard-Baron,
  • Guillaume Chevrel,
  • Céline Clergue,
  • Kubab Sabah,
  • Laurence Courdavault Vagh Weinmann,
  • Malo Emery,
  • Claudio Garcia-Sanchez,
  • Ferhat Meziani,
  • Louis-Marie Jandeaux,
  • Samira Fafi-Kremer,
  • Sébastien Preau,
  • Aurélie Guignon,
  • Evelyne Schvoerer,
  • Charles Damoisel,
  • Nicolas Brechot,
  • Hélène Péré,
  • François Beloncle,
  • Francoise Lunel Fabiani,
  • Jean-Marc Tadié,
  • Delamaire Flora,
  • Vincent Thibaut,
  • Béatrice La Combe,
  • Séverine Haouisee,
  • Alexandre Boyer,
  • Sonia Burrel,
  • Jean-Christophe Plantier,
  • Emmanuel Canet,
  • Berthe Marie Imbert,
  • Clément Saccheri,
  • Valérie Giordanengo,
  • Sami Hraeich,
  • Pierre-Edouard Fournier,
  • Philippe Colson,
  • Anaïs Dartevel,
  • Sylvie Larrat,
  • Guillaume Thiery,
  • Sylvie Pillet,
  • Kada Klouche,
  • Edouard Tuaillon,
  • Cécile Aubron,
  • Adissa Tran,
  • Sophie Vallet,
  • Pierre-Emmanuel Charles,
  • Alexis De Rougemont,
  • Bertrand Souweine,
  • Cecile Henquell,
  • Bruno Mourvillier,
  • Damien Du Cheyron,
  • Nefert Candace Dossou,
  • Gaël Piton,
  • Quentin Lepiller

摘要

Introduction

The clinical presentation of critically ill patients with coronavirus disease 2019 (COVID-19) has evolved significantly with the emergence of the Omicron variant. Current intensive care unit (ICU) admissions involve patients with diverse comorbidities and immune statuses, highlighting the need to redefine homogeneous phenotypic subgroups within this population. This study aimed to characterize distinct clinical phenotypes among critically ill patients with COVID-19 and acute respiratory failure.

Methods

This multicenter prospective substudy of the SEVARVIR cohort included adult patients from 39 French ICUs between December 2021 and October 2024 with acute respiratory failure and infected with the Omicron variant. Clustering analysis was conducted using Kohonen’s self-organizing maps (SOMs) and validated with ClinTrajan, two unsupervised clustering methods, to identify homogeneous patient phenotypes.

Results

During the study period, 777 patients with Omicron infection were included, and 7 distinct clinical clusters were identified. Clusters 1 and 2 included patients with metabolic and cardiovascular comorbidities. Cluster 3 featured younger, mildly ill patients with isolated chronic respiratory failure, while cluster 4 comprised older male patients with isolated respiratory failure. Cluster 5 included patients with isolated hematologic malignancies, cluster 6 patients with multiorgan failure, and cluster 7 organ transplant recipients, with high severity scores and impaired renal function. ICU management varied substantially across clusters. Patients in clusters 5 and 7 had the highest requirements for organ support, with frequent use of invasive mechanical ventilation, vasopressors (cluster 6), and renal replacement therapy (cluster 7). Dexamethasone and tocilizumab were most commonly prescribed in cluster 4 (91.3% and 30.2%, respectively). Mortality at day 28 varied significantly across clusters, ranging from 13.1% in cluster 3 to 41.1% in cluster 6.

Conclusions

This clustering analysis highlights, for the first time, the clinical heterogeneity of critically ill patients infected with Omicron, identifying seven distinct clusters with varying clinical presentations, management strategies and outcomes. These findings underscore the relevance of a phenotype-driven approach to support personalized treatment strategies and guide future clinical trials.

Trial Registration

Clinicaltrials.gov, NCT05162508.

A Graphical Abstract is available for this article.

Graphical Abstract