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

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

doi:10.1038/s41598-025-95122-7

David M. Smadja

Université René Descartes (Paris V)

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^-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.

How to cite this publication

David M. Smadja, David M. Smadja, Clément Massonnaud, Clément Massonnaud, Aurélien Philippe, Aurélien Philippe, Mickaël Rosa, Mickaël Rosa, Sophie Luneau, Sophie Luneau, Antoine Rauch, Antoine Rauch, Nathan Peiffer‐Smadja, Nathan Peiffer‐Smadja, Amandine Gagneux‐Brunon, Amandine Gagneux‐Brunon, Julien Poissy, Julien Poissy, Maxime Gruest, Maxime Gruest, Alexandre Ung, Alexandre Ung, Valérie Pourcher, Valérie Pourcher, F. Raffi, F. Raffi, Lionel Piroth, Lionel Piroth, Kévin Bouiller, Kévin Bouiller, Hélène Espérou, Hélène Espérou, Christelle Delmas, Christelle Delmas, Drifa Belhadi, Drifa Belhadi, Alpha Diallo, Alpha Diallo, Juliette Saillard, Juliette Saillard, Aline Dechanet, Aline Dechanet, Noémie Mercier, Noémie Mercier, Axelle Dupont, Axelle Dupont, François‐Xavier Lescure, François‐Xavier Lescure, François Goehringer, François Goehringer, Stéphane Jauréguiberry, Stéphane Jauréguiberry, François Danion, François Danion, Violaine Tolsma, Violaine Tolsma, André Cabié, André Cabié, Johan Courjon, Johan Courjon, Sylvie Leroy, Sylvie Leroy, Joy Mootien, Joy Mootien, Bruno Mourvillier, Bruno Mourvillier, Sébastien Gallien, Sébastien Gallien, Jean‐Philippe Lanoix, Jean‐Philippe Lanoix, Elisabeth Botelho-Nevers, Elisabeth Botelho-Nevers, Florent Wallet, Florent Wallet, Jean‐Christophe Richard, Jean‐Christophe Richard, Jean Reuter, Jean Reuter, Alexandre Gaymard, Alexandre Gaymard, Richard Greil, Richard Greil, Guillaume Martin‐Blondel, Guillaume Martin‐Blondel, Claire Andréjak, Claire Andréjak, Yazdan Yazdanpanah, Yazdan Yazdanpanah, Charles Burdet, Charles Burdet, Jean‐Luc Diehl, Jean‐Luc Diehl, Maya Hites, Maya Hites, Florence Ader, Florence Ader, Sophie Susen, Sophie Susen, France Mentré, France Mentré, Annabelle Dupont, Annabelle Dupont (2025). sST2 is a key outcome biomarker in COVID-19: insights from discovery randomized trial. , 15(1), DOI: https://doi.org/10.1038/s41598-025-95122-7.

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

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David M. Smadja

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