Early measurement of blood sST2 is a good predictor of death and poor outcomes in patients admitted for COVID-19 infection

Abstract

ImportanceAlthough several biomarkers have shown correlation to prognosis in COVID-19 patients, their clinical value is limited because of lack of specificity, suboptimal sensibility, or poor dynamic behavior.ObjectiveIn search of better prognostic markers in COVID-19, we hypothesized that circulating soluble ST2 (sST2) could be associated to a worse outcome, prompted by our previous knowledge of sST2 involvement in heart failure-associated lung deterioration, and by mounting evidence favoring a role of IL-33/ST2 axis in the disease.Design, Setting and participantsOne hundred and fifty-two patients admitted for confirmed COVID-19 infection were included in a prospective non-interventional, observational study carried out in a tertiary teaching center. Blood samples were drawn at admission, 48-72 hours later and at discharge. sST2 concentrations, and routine blood laboratory were analyzed.Main outcomesPrimary end-points were admission at intensive care unit (ICU) and, mortality. Other outcomes were a need for high oxygen flow therapy (HOF) or increasing treatment at 48/72 hours.ResultsMedian age was 57.5 years (SD: 12.8), 60.4% males. Ten per cent of patients (n=15) were derived to ICU and/or died during admission. The rest stayed hospitalized 8(IQR:6) days on average. About 34% (n=47), 38% (n=53) and 48.5% (n=66) needed HOF, up-titrate therapy or both, respectively.Median (IQR) sST2 serum concentration (ng/mL) rose to 53.1(30.9) at admission, peaked at 48-72h (79.5[64]) and returned to admission levels at discharge (44.9[36.7]), remaining significantly elevated above healthy donor values (18.6[15.1]).A concentration of sST2 above 58.9 ng/mL identified patients progressing to ICU admission or death. These results remained significant after multivariable analysis. The area under the receiver operating characteristics curve (AUC) of sST2 for the occurrence of end-points was 0.776 (p=0.001). Admission sST2 was higher in patients who needed up-tritate therapy.Conclusions and relevanceIn patients admitted for COVID-19 infection, measurement of sST2 measurement early within 24h after at admission was able to identify patients at risk of severe complications or death.

Early Measurement of Blood sST2 Is a Good Predictor of Death and Poor Outcomes in Patients Admitted for COVID-19 Infection

“…Since we reported our results in preprinted form [25] there have been several studies determining sST2 blood levels in COVID-19 patients. As the IL-33/ST2 axis is involved in immune response to viral infections, Zeng et al measured IL-33 and sST2 in 80 COVID-19 patients [26].…”

Astegolimab or Efmarodocokin Alfa in Patients With Severe COVID-19 Pneumonia: A Randomized, Phase 2 Trial*

“…Baseline serum sST2 in COVID-19 patients was increased (13.8–1,600 ng/mL; mean, 116 ng/mL; Table S6 , http://links.lww.com/CCM/H235) compared with healthy volunteers (HVs) (24). Similar to other serum proteins (25), astegolimab binding is predicted to increase the half-life of sST2, resulting in sST2 elevations.…”

“…Sparse sample collection affected interpretability of day 15 and 21 data (samples were only collected at these timepoints from patients who remained hospitalized). Baseline serum sST2 in COVID-19 patients was increased (13.8-1,600 ng/mL; mean, 116 ng/mL; Table S6, http://links.lww.com/CCM/H235) compared with healthy volunteers (HVs) (24). Similar to other serum proteins (25), astegolimab binding is predicted to increase the half-life of sST2, resulting in sST2 elevations.…”