Soluble ST2 concentrations associate with in-hospital mortality and need for mechanical ventilation in unselected patients with COVID-19

Abstract

Objective: Soluble ST2 (sST2) reflects inflammation, endothelial dysfunction and myocardial fibrosis, is produced in the lungs and is an established biomarker in heart failure. We sought to determine the role of sST2 in COVID-19 by assessing pathophysiological correlates and its association to in-hospital outcomes.

Methods: We enrolled 123 consecutive, hospitalised patients with COVID-19 in the prospective, observational COVID-19 MECH study. Biobank samples were collected at baseline, day 3 and day 9. The key exposure variable was sST2, and the outcome was ICU treatment with mechanical ventilation or in-hospital death.

Results: Concentrations of sST2 at baseline was median 48 (IQR 37-67) ng/mL, and 74% had elevated concentrations (>37.9 ng/mL). Higher baseline sST2 concentrations were associated with older age, male sex, white race, smoking, diabetes, hypertension and chronic kidney disease. Baseline sST2 also associated with the presence of SARS-CoV-2 viraemia, lower oxygen saturation, higher respiratory rate and increasing concentrations of biomarkers reflecting inflammation, thrombosis and cardiovascular disease. During the hospitalisation, 8 (7%) patients died and 27 (22%) survivors received intensive care unit (ICU) treatment. Baseline sST2 concentrations demonstrated a graded association with disease severity (median, IQR): medical ward 43 (36-59) ng/mL; ICU 67 (39-104) ng/mL and non-survivors 107 (72-116) ng/mL (p<0.001 for all comparisons). These associations persisted at day 3 and day 9 .

Conclusions: sST2 concentrations associate with SARS-CoV-2 viraemia, hypoxaemia and concentrations of inflammatory and cardiovascular biomarkers. There was a robust association between baseline sST2 and disease severity that was independent of, and superior to, established risk factors. sST2 reflects key pathophysiology and may be a promising biomarker in COVID-19.

Trial registration number: NCT04314232.

Keywords: COVID-19; biomarkers; risk factors.

Conflict of interest statement

Competing interests: TO has served on advisory boards for Abbott Diagnostics, Roche Diagnostics and Bayer and has received research support from Abbott Diagnostics, Novartis, Roche Diagnostics, Singulex and SomaLogic via Akershus University Hospital, and speaker’s or consulting honoraria from Roche Diagnostics, Siemens Healthineers and CardiNor. PLM has served on advisory boards for AstraZeneca, Boehringer Ingelheim, Novartis and Novo Nordisk and has received consulting honoraria from AstraZeneca, AmGen, Boehringer Ingelheim, Novartis and Novo Nordisk.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Concentrations of soluble ST2 at baseline, day 3 and day 9 in hospitalised COVID-19 patients treated at the medical ward, ICU and in non-survivors. Bars represent median concentration and whiskers quartile 1 and quartile 3. P value is for comparison of concentrations in patients treated in the ICU or non-survivors to patients treated in the medical ward, after adjustment for age, sex, race, cardiovascular disease, body mass index and estimated glomerular filtration rate. ICU, intensive care unit.