sST2 is a key outcome biomarker in COVID-19: insights from discovery randomized trial
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Smadja, David | Massonnaud, Clément | Philippe, Aurélien | Rosa, Mickael | Luneau, Sophie | Rauch, Antoine | Peiffer-Smadja, Nathan | Gagneux-Brunon, Amandine | Poissy, Julien | Gruest, Maxime | Ung, Alexandre | Pourcher, Valérie | Raffi, François | Piroth, Lionel | Bouiller, Kévin | Esperou, Hélène | Delmas, Christelle | Belhadi, Drifa | Diallo, Alpha | Saillard, Juliette | Dechanet, Aline | Mercier, Noémie | Dupont, Axelle | Lescure, François-Xavier | Goehringer, François | Jaureguiberry, Stéphane | Danion, François | Tolsma, Violaine | Cabie, André | Courjon, Johan | Leroy, Sylvie | Mootien, Joy | Mourvillier, Bruno | Gallien, Sébastien | Lanoix, Jean-Philippe | Botelho-Nevers, Elisabeth | Wallet, Florent | Richard, Jean-Christophe | Reuter, Jean | Gaymard, Alexandre | Greil, Richard | Martin-Blondel, Guillaume | Andrejak, Claire | Yazdanpanah, Yazdan | Burdet, Charles | Diehl, Jean-Luc | Hites, Maya | Ader, Florence | Susen, Sophie | Mentré, France | Dupont, Annabelle | Couffin-Cadièrgues, Sandrine | Lamprecht, Bernd | Joannidis, Michael | Egle, Alexander | Altdorfer, Antoine | Fraipont, Vincent | Belkhir, Leila | Verschelden, Gil | Bougon, David | Delbove, Agathe | Gousseff, Marie | Saidani, Nadia | Wattecamps, Guilhem | Djossou, Félix | Epelboin, Loïc | Roger, Pierre-Alexandre | Zerbib, Yoann | Bouiller, Kevin | Chirouze, Catherine | Navellou, Jean-Christophe | Boyer, Alexandre | Cazanave, Charles | Duvignaud, Alexandre | Gruson, Didier | Malvy, Denis | Lessire, Henry | Martinot, Martin | Andreu, Pascal | Blot, Mathieu | Quenot, Jean Pierre | Epaulard, Olivier | Terzi, Nicolas | Faure, Karine | Faure, Emmanuel | Nseir, Saad | Argaud, Laurent | Ferry, Tristan | Perpoint, Thomas | Piriou, Vincent | Textoris, Julien | Valour, Florent | Cabié, André | Turmel, Jean-Marie | Chabartier, Cyrille | Gaci, Rostane | Robert, Céline | Makinson, Alain | Le Moing, Vincent | Klouche, Kada | Hinschberger, Olivier | Gibot, Sébastien | Kimmoun, Antoine | Lefevre, Benjamin | Boutoille, David | Canet, Emmanuel | Gaborit, Benjamin | Le Turnier, Paul | Reignier, Jean | Dellamonica, Jean | Marquette, Charles-Hugo | Loubet, Paul | Roger, Claire | Sotto, Albert | Bruel, Cédric | Pilmis, Benoît | Geri, Guillaume | Rouveix-Nordon, Elisabeth | Bouchaud, Olivier | Figueiredo, Samy | Monnet, Xavier | Bouadma, Lila | Timsit, Jean-François | Kerneis, Solen | Lachâtre, Marie | Launay, Odile | Mira, Jean-Paul | Mayaux, Julien | Aboab, Jérôme | Crockett, Flora | Sayre, Naomi | Dubost, Clément | Ficko, Cécile | Lebeaux, David | Mekontso-Dessap, Armand | Le Pavec, Jérôme | Stefan, Francois | Ait-Oufella, Hafid | Lacombe, Karine | Molina, Jean-Michel | Fartoukh, Murielle | Pialoux, Gilles | Bani-Sadr, Firouzé | Benezit, François | Laine, Fabrice | Laviolle, Bruno | Le Tulzo, Yves | Revest, Matthieu | Thiery, Guillaume | Hansmann, Yves | Meziani, Ferhat | Oulehri, Walid | Tacquard, Charles | Bounes-Vardon, Fanny | Murris-Espin, Marlène | Riu-Poulenc, Béatrice | Jeanmichel, Vanessa | Senneville, Eric | Bernard, Louis | Garot, Denis | Staub, Thérèse | Berna, Marc | Braz, Sandra | Ribeiro, Joao Miguel Ferreira | Paiva, José-Artur | Roncon-Albuquerque, Roberto | Leveau, Benjamin
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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.
