sST2 is a key outcome biomarker in COVID-19: insights from discovery randomized trial

We investigated whether baseline levels of biomarkers related to endotheliopathy, thromboinflammation, and fibrosis were associated with clinical outcomes in hospitalized COVID-19 patients. We analyzed the associations between baseline levels of 21 biomarkers and time to hospital discharge and change in NEWS-2 score in patients from DisCoVeRy trial. We fitted multivariate models adjusted for baseline ISARIC 4C score, disease severity, D-dimer values, and treatment regimen. Between March 22 and June 29, 2020, 603 participants were randomized; 454 had a sample collected at baseline and analyzed. The backward selection of multivariate models showed that higher baseline levels of soluble suppressor of tumorigenicity 2 (sST2) and nucleosomes were statistically associated with a lower chance of hospital discharge before day 29 (sST2: aHR 0.24, 95% CI [0.15-0.38], p < 10<sup>-9</sup>; nucleosomes: aHR 0.62, 95% CI [0.48-0.81], p < 10<sup>-3</sup>). Likewise, higher levels of baseline sST2 were statistically associated with lower changes in the NEWS-2 score between baseline and day 15 (adjusted beta 4.47, 95% CI [2.65-6.28], p < 10<sup>-5</sup>). Moreover, we evaluated sST2 involvement in a confirmation cohort (SARCODO study, 103 patients) and found that elevated baseline sST2 levels were significantly associated with lower rates of hospital discharge before day 29 and a higher model performance (AUC at day 29 of 92%) compared to models without sST2. sST2 emerged as an independent predictor of clinical outcomes in two large cohort of hospitalized COVID-19 patients, warranting further investigation to elucidate its role in disease progression and potential as a therapeutic target.

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Journal
Scientific Reports
Published
2025-04-24
DOI
https://doi.org/10.1038/s41598-025-95122-7
Citations
4
Primary Topic
IL-33, ST2, and ILC Pathways
Type
article
Field-Weighted Citation Impact
3.19

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article

sST2 is a key outcome biomarker in COVID-19: insights from discovery randomized trial

Clément Massonnaud, Charles Burdet, Guillaume Martin‐Blondel, Sébastien Gallien et al.
4 citations
Scientific Reports
IL-33, ST2, and ILC Pathways
3.19
article

sST2 is a key outcome biomarker in COVID-19: insights from discovery randomized trial

Clément Massonnaud, Charles Burdet, Guillaume Martin‐Blondel, Sébastien Gallien, Mickaël Rosa, David M. Smadja, Jean‐Philippe Lanoix, Alexandre Gaymard, Hélène Espérou, France Mentré, Johan Courjon, Richard Greil, Lionel Piroth, Jean‐Luc Diehl, Antoine Rauch, Nathan Peiffer‐Smadja, Aline Dechanet, Sylvie Leroy, André Cabié, Drifa Belhadi, Maya Hites, Axelle Dupont, Florence Ader, Sophie Susen, Amandine Gagneux‐Brunon, Alpha Diallo, Maxime Gruest, Jean‐Christophe Richard, Bruno Mourvillier, Florent Wallet, Aurélien Philippe, Alexandre Ung, François Goehringer, François Danion, Annabelle Dupont, Christelle Delmas, Stéphane Jauréguiberry, Joy Mootien, Sophie Luneau, Jean Reuter, Claire Andréjak, Yazdan Yazdanpanah, Juliette Saillard, Violaine Tolsma, Kévin Bouiller, F. Raffi, François‐Xavier Lescure, Valérie Pourcher, Noémie Mercier, Elisabeth Botelho-Nevers, Julien Poissy
article en
4 citations

Abstract

We investigated whether baseline levels of biomarkers related to endotheliopathy, thromboinflammation, and fibrosis were associated with clinical outcomes in hospitalized COVID-19 patients. We analyzed the associations between baseline levels of 21 biomarkers and time to hospital discharge and change in NEWS-2 score in patients from DisCoVeRy trial. We fitted multivariate models adjusted for baseline ISARIC 4C score, disease severity, D-dimer values, and treatment regimen. Between March 22 and June 29, 2020, 603 participants were randomized; 454 had a sample collected at baseline and analyzed. The backward selection of multivariate models showed that higher baseline levels of soluble suppressor of tumorigenicity 2 (sST2) and nucleosomes were statistically associated with a lower chance of hospital discharge before day 29 (sST2: aHR 0.24, 95% CI [0.15-0.38], p < 10<sup>-9</sup>; nucleosomes: aHR 0.62, 95% CI [0.48-0.81], p < 10<sup>-3</sup>). Likewise, higher levels of baseline sST2 were statistically associated with lower changes in the NEWS-2 score between baseline and day 15 (adjusted beta 4.47, 95% CI [2.65-6.28], p < 10<sup>-5</sup>). Moreover, we evaluated sST2 involvement in a confirmation cohort (SARCODO study, 103 patients) and found that elevated baseline sST2 levels were significantly associated with lower rates of hospital discharge before day 29 and a higher model performance (AUC at day 29 of 92%) compared to models without sST2. sST2 emerged as an independent predictor of clinical outcomes in two large cohort of hospitalized COVID-19 patients, warranting further investigation to elucidate its role in disease progression and potential as a therapeutic target.

Scientific ReportsVol. 15(1)
Université Claude Bernard Lyon 1 (FR), Hôpital Necker-Enfants Malades (FR), Centre National de la Recherche Scientifique (FR), Cliniques Universitaires Saint-Luc (BE), Université Libre de Bruxelles (BE), Université Toulouse III - Paul Sabatier (FR), Innsbruck Medical University (AT), Université de Bordeaux (FR), Inserm (FR), Centre Hospitalier de Luxembourg (LU), Université de Bourgogne (FR), Université Fédérale de Toulouse Midi-Pyrénées (FR), Universität Innsbruck (AT), Université Paris-Est Créteil (FR), Université de Montpellier (FR), Université Côte d'Azur (FR), Université Paris Cité (FR), Paracelsus Medical University (AT), Centre Hospitalier Universitaire de Grenoble (FR), Institut Pasteur de Lille (FR), Hospital de São João (PT), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nice (FR), Centre Hospitalier Universitaire de Nantes (FR), Centre Hospitalier Universitaire Henri-Mondor (FR), Centre Hospitalier Universitaire de Toulouse (FR), Sorbonne Université (FR), Centre Hospitalier Chrétien (BE), Hôpital Louis-Mourier (FR), Centre Hospitalier Universitaire de Besançon (FR), Hôpital de la Croix-Rousse (FR), Sorbonne Paris Cité (FR), Hôpital Cochin (FR), Centre Hospitalier Universitaire de Montpellier (FR), Centre Hospitalier Universitaire de Tours (FR), Centre Hospitalier Universitaire Amiens-Picardie (FR), Assistance Publique – Hôpitaux de Paris (FR), Centre Hospitalier Régional et Universitaire de Nancy (FR), Hospices Civils de Lyon (FR), Hôpital Européen Georges-Pompidou (FR), Hôpital Saint-Antoine (FR), Centre Hospitalier Universitaire Brugmann (BE), Centre Hospitalier Universitaire de Nîmes (FR), Laboratoire Chrono-Environnement (FR), Fédération Hospitalo-Universitaire, Paris Center for Microbiome Medicine (FR), Centre Hospitalier Universitaire de Reims (FR), Institut Pasteur de la Guyane (GF), Bordeaux Population Health (FR), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (FR), Centro Hospitalar Lisboa Norte (PT), Centre Hospitalier de Tourcoing (FR), Centre Hospitalier Andrée Rosemon (GF), CHU Dijon Bourgogne (FR), Université Bourgogne Franche-Comté (FR), Centre Méditerranéen de Médecine Moléculaire (FR), Kepler Universitätsklinikum (AT), Hôpitaux Universitaires Paris-Ouest (FR), Hôpital Marie Lannelongue (FR), Pitié-Salpêtrière Hospital (FR), Centre Hospitalier du Mans (FR), Centre d'Investigation Clinique de Nantes (FR), Centre d'Immunologie et des Maladies Infectieuses (FR), Hôpital Avicenne (FR), Hôpitaux Universitaires Henri-Mondor (FR), Centre Hospitalier Annecy Genevois (FR), Institut Pierre Louis d‘Épidémiologie et de Santé Publique (FR), Centre Hospitalier Universitaire de Liège (BE), Centre Hospitalier Universitaire de Martinique (MQ), Virologie et Pathologies Humaines (FR), Centre Hospitalier de La Rochelle (FR), Centre Hospitalier Universitaire Pointe-à-Pitre (GP), Hôpital Saint-Louis (FR), Hôpital Bichat-Claude-Bernard (FR), Hôpitaux Universitaires de Strasbourg (FR), Groupe Hospitalier de la Région de Mulhouse et Sud Alsace (FR), Centre Hospitalier Universitaire de Rennes (FR), Centre Hospitalier Universitaire de Saint-Étienne (FR), GIS-Institut pour la Recherche en Santé Publique (FR), Institut de Pharmacologie Moléculaire et Cellulaire (FR), Centre International de Recherche en Infectiologie (FR), Bicêtre Hospital (FR), Hôpital Tenon (FR), Université de Picardie Jules Verne (FR), Institut National des Sciences Appliquées de Lyon (FR), Université de Montréal (CA), Université de Lorraine (FR), Université de Franche-Comté (FR), UCLouvain (BE), Université de Reims Champagne-Ardenne (FR), Nantes Université (FR)
Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation de France
Openalex Percentile: Top 8%
IL-33, ST2, and ILC Pathways
3.19
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