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<p>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], <i>p</i> &lt; 10<sup>−9</sup>; nucleosomes: aHR 0.62, 95% CI [0.48–0.81], <i>p</i> &lt; 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], <i>p</i> &lt; 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月24日

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  • David M. Smadja,
  • Clément R. Massonnaud,
  • Aurélien Philippe,
  • Mickael Rosa,
  • Sophie Luneau,
  • Antoine Rauch,
  • Nathan Peiffer-Smadja,
  • Amandine Gagneux-Brunon,
  • Julien Poissy,
  • Maxime Gruest,
  • Alexandre Ung,
  • Valérie Pourcher,
  • François Raffi,
  • Lionel Piroth,
  • Kévin Bouiller,
  • Hélène Esperou,
  • Christelle Delmas,
  • Drifa Belhadi,
  • Alpha Diallo,
  • Juliette Saillard,
  • Aline Dechanet,
  • Noémie Mercier,
  • Axelle Dupont,
  • François-Xavier Lescure,
  • François Goehringer,
  • Stéphane Jaureguiberry,
  • François Danion,
  • Violaine Tolsma,
  • André Cabie,
  • Johan Courjon,
  • Sylvie Leroy,
  • Joy Mootien,
  • Bruno Mourvillier,
  • Sébastien Gallien,
  • Jean-Philippe Lanoix,
  • Elisabeth Botelho-nevers,
  • Florent Wallet,
  • Jean-Christophe Richard,
  • Jean Reuter,
  • Alexandre Gaymard,
  • Richard Greil,
  • Guillaume Martin-Blondel,
  • Claire Andrejak,
  • Yazdan Yazdanpanah,
  • Charles Burdet,
  • Jean-Luc Diehl,
  • Maya Hites,
  • Florence Ader,
  • Sophie Susen,
  • France Mentré,
  • Annabelle Dupont,
  • Sandrine Couffin-Cadièrgues,
  • Hélène Esperou,
  • Bernd Lamprecht,
  • Michael Joannidis,
  • Alexander Egle,
  • Richard Greil,
  • Antoine Altdorfer,
  • Vincent Fraipont,
  • Leila Belkhir,
  • Maya Hites,
  • Gil Verschelden,
  • Violaine Tolsma,
  • David Bougon,
  • Agathe Delbove,
  • Marie Gousseff,
  • Nadia Saidani,
  • Guilhem Wattecamps,
  • Félix Djossou,
  • Loïc Epelboin,
  • Jean-Philippe Lanoix,
  • Pierre-Alexandre Roger,
  • Claire Andrejak,
  • Yoann Zerbib,
  • Kevin Bouiller,
  • Catherine Chirouze,
  • Jean-Christophe Navellou,
  • Alexandre Boyer,
  • Charles Cazanave,
  • Alexandre Duvignaud,
  • Didier Gruson,
  • Denis Malvy,
  • Henry Lessire,
  • Martin Martinot,
  • Pascal Andreu,
  • Mathieu Blot,
  • Lionel Piroth,
  • Jean Pierre Quenot,
  • Olivier Epaulard,
  • Nicolas Terzi,
  • Karine Faure,
  • Emmanuel Faure,
  • Julien Poissy,
  • Saad Nseir,
  • Florence Ader,
  • Laurent Argaud,
  • Tristan Ferry,
  • Thomas Perpoint,
  • Vincent Piriou,
  • Jean-Christophe Richard,
  • Julien Textoris,
  • Florent Valour,
  • Florent Wallet,
  • André Cabié,
  • Jean-Marie Turmel,
  • Cyrille Chabartier,
  • Rostane Gaci,
  • Céline Robert,
  • Alain Makinson,
  • Vincent Le Moing,
  • Kada Klouche,
  • Olivier Hinschberger,
  • Joy Mootien,
  • Sébastien Gibot,
  • François Goehringer,
  • Antoine Kimmoun,
  • Benjamin Lefevre,
  • David Boutoille,
  • Emmanuel Canet,
  • Benjamin Gaborit,
  • Paul Le Turnier,
  • François Raffi,
  • Jean Reignier,
  • Johan Courjon,
  • Jean Dellamonica,
  • Sylvie Leroy,
  • Charles-Hugo Marquette,
  • Paul Loubet,
  • Claire Roger,
  • Albert Sotto,
  • Cédric Bruel,
  • Benoît Pilmis,
  • Guillaume Geri,
  • Elisabeth Rouveix-Nordon,
  • Olivier Bouchaud,
  • Samy Figueiredo,
  • Stéphane Jaureguiberry,
  • Xavier Monnet,
  • Lila Bouadma,
  • François-Xavier Lescure,
  • Nathan Peiffer-Smadja,
  • Jean-François Timsit,
  • Yazdan Yazdanpanah,
  • Solen Kerneis,
  • Marie Lachâtre,
  • Odile Launay,
  • Jean-Paul Mira,
  • Julien Mayaux,
  • Valérie Pourcher,
  • Jérôme Aboab,
  • Flora Crockett,
  • Naomi Sayre,
  • Clément Dubost,
  • Cécile Ficko,
  • David Lebeaux,
  • Sébastien Gallien,
  • Armand Mekontso-Dessap,
  • Jérôme Le Pavec,
  • Francois Stefan,
  • Hafid Ait-Oufella,
  • Karine Lacombe,
  • Jean-Michel Molina,
  • Murielle Fartoukh,
  • Gilles Pialoux,
  • Firouzé Bani-Sadr,
  • Bruno Mourvillier,
  • François Benezit,
  • Fabrice Laine,
  • Bruno Laviolle,
  • Yves Le Tulzo,
  • Matthieu Revest,
  • Elisabeth Botelho-Nevers,
  • Amandine Gagneux-Brunon,
  • Guillaume Thiery,
  • François Danion,
  • Yves Hansmann,
  • Ferhat Meziani,
  • Walid Oulehri,
  • Charles Tacquard,
  • Fanny Bounes-Vardon,
  • Guillaume Martin-Blondel,
  • Marlène Murris-Espin,
  • Béatrice Riu-Poulenc,
  • Vanessa Jeanmichel,
  • Eric Senneville,
  • Louis Bernard,
  • Denis Garot,
  • Jean Reuter,
  • Thérèse Staub,
  • Marc Berna,
  • Sandra Braz,
  • Joao Miguel Ferreira Ribeiro,
  • José-Artur Paiva,
  • Roberto Roncon-Albuquerque,
  • Benjamin Leveau

摘要

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 < 10−9; nucleosomes: aHR 0.62, 95% CI [0.48–0.81], p < 10−3). 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 < 10−5). 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.