Plasma sST2 Provides Prognostic Information in COVID-19 Respiratory Failure

Elevated inflammatory markers are known to correlate with disease progression and mortality in COVID-19–related acute hypoxemic respiratory failure (COV19-AHRF). However, there's a critical need for specific measures of lung injury and predictors of ventilator dependence to guide treatment and prognostication.

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As reported in Critical Care Medicine, Massachusetts General Hospital researchers previously found that plasma concentration of soluble suppression of tumorigenicity-2 (sST2), a member of the interleukin-1 receptor family, associates with ventilator dependence and mortality in AHRF.

Now, in Critical Care Explorations, Jehan W. Alladina, MD, physician in the Division of Pulmonary and Critical Care Medicine at Mass General, and Benjamin D. Medoff, MD, chief of the division, and colleagues report that sST2 similarly reflects ongoing lung injury in COV19-AHRF.

Study Methods

The researchers studied 149 adults with COVID-19 who were consecutively admitted to Mass General between April 25 and June 25, 2020. 72 were admitted to the ICU with AHRF, and 77 had mild hypoxemia managed with supplemental oxygen.

Plasma samples were collected from excess blood draws daily for the first six days after admission and on the day of extubation in intubated patients. Plasma sST2 values were logarithmically transformed to analyze their association with 30-day outcomes.

ICU vs. Non-ICU Patients

Baseline sST2 concentrations were significantly higher in ICU patients than non-ICU patients (median 85 ng/mL vs. 46 ng/mL; P<0.0001).

ICU Mortality

42 ICU patients (58%) were successfully extubated; the others were reintubated, had a tracheostomy placed or died by day 30.

• Among ICU patients who died by day 30, baseline log-sST2 concentrations were significantly higher than in survivors (median 2.08 ng/mL vs. 1.94 ng/mL; P<0.05)
• Baseline ferritin, d-dimer and C-reactive protein did not differ significantly between the survivor and non-survivor groups
• Initial PaO₂/FiO₂ and modified Sequential Organ Failure Assessment (mSOFA) score were also similar between the groups

Ventilator Dependence

• In an analysis adjusted for age and mSOFA score, elevated log-sST2 was associated with decreased odds of successful extubation (OR, 0.10 for every 1-log unit increase; P=0.03)
• The last measured log-sST2 was higher in patients who required reintubation or tracheostomy than in successfully extubated patients (median 2.10 ng/mL vs. 1.87 ng/mL; P=0.03) with an area under the receiver operating curve of 0.70 (P=0.03)
• The last measured ferritin, d-dimer, C-reactive protein, mSOFA score and PaO₂/FiO₂ were similar in successfully extubated patients and in others

Applying the Findings

These data suggest that in patients with CoV19-AHRF, elevated sST2 concentrations over the course of an ICU admission signify persistent lung injury. Measuring sST2 in addition to assessing illness severity and oxygenation may provide important prognostic information about a patient's clinical trajectory and readiness for ventilator liberation.

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