Journal Article

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

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

2025

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/326/596 / 692/308/53 / 692/53 / 692/699/75/593 / Aged / Angiogenesis / Biomarkers - blood / COVID-19 / COVID-19 - blood / COVID-19 - diagnosis / COVID-19 - pathology / Female / Fibrin Fibrinogen Degradation Products / Fibrosis / Hospitalization / Human health and pathology / Humanities and Social Sciences / Humans / Infectious diseases / Interleukin-1 Receptor-Like 1 Protein - blood / Life Sciences / Male / Microbiology and Parasitology / Middle Aged / multidisciplinary / Nucleosomes - metabolism / Prognosis / SARS-CoV-2 / Science / Science (multidisciplinary) / Severity of Illness Index / ST2 / Virology