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Clinical Trial
. 2025 Apr 24;15(1):14348.
doi: 10.1038/s41598-025-95122-7.

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

David M Smadja #  1   2 , Clément R Massonnaud #  3   4 , Aurélien Philippe #  5   6 , Mickael Rosa #  7 , Sophie Luneau  6 , Antoine Rauch  7 , Nathan Peiffer-Smadja  4   8 , Amandine Gagneux-Brunon  9   10 , Julien Poissy  7 , Maxime Gruest  6 , Alexandre Ung  7 , Valérie Pourcher  11 , François Raffi  12 , Lionel Piroth  13 , Kévin Bouiller  14 , Hélène Esperou  15 , Christelle Delmas  4 , Drifa Belhadi  3   4 , Alpha Diallo  16 , Juliette Saillard  16 , Aline Dechanet  3   4 , Noémie Mercier  16 , Axelle Dupont  4   8 , François-Xavier Lescure  4   8 , François Goehringer  17 , Stéphane Jaureguiberry  18   19 , François Danion  20 , Violaine Tolsma  21 , André Cabie  22   23 , Johan Courjon  24   25 , Sylvie Leroy  26   27   28 , Joy Mootien  29 , Bruno Mourvillier  30 , Sébastien Gallien  31   32 , Jean-Philippe Lanoix  33   34 , Elisabeth Botelho-Nevers  9   10 , Florent Wallet  35 , Jean-Christophe Richard  36   37 , Jean Reuter  38 , Alexandre Gaymard  39   40 , Richard Greil  41 , Guillaume Martin-Blondel  42   43 , Claire Andrejak  44 , Yazdan Yazdanpanah  4   8 , Charles Burdet  3   4 , Jean-Luc Diehl  5   45 , Maya Hites  46 , Florence Ader  47   48 , Sophie Susen  7 , France Mentré #  3   4 , Annabelle Dupont #  7 ; Discovery Study Group
Collaborators, Affiliations
Clinical Trial

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

David M Smadja et al. Sci Rep. .

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.

Keywords: Angiogenesis; COVID-19; Fibrosis; SARS-CoV-2; ST2.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of discovery trial.
Fig. 2
Fig. 2
Final multivariate models with association between the log10 baseline concentration of the selected biomarkers and outcomes.
Fig. 3
Fig. 3
Association between ST2/IL-33R values and (A) the time to hospital discharge before day 29, (B) the change in NEWS2 between baseline and day 15, in DisCoVeRy.
Fig. 4
Fig. 4
Time-dependent areas under ROC curve for the proportional-hazards models of time to hospital discharge before day 29 for different models with (A) DisCoVeRy study. (B) Confirmation cohort: SARCODO study. All models for DisCoVeRy are also adjusted for the treatment strategy.
Fig. 5
Fig. 5
Scatterplots of significant correlations (P < 0.05) between log10 ST2/IL-33R (x-axis) and log10 of biomarkers concentrations (y-axis), in DisCoVeRy.
See this image and copyright information in PMC

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