Soluble TREM-1 plasma concentration predicts poor outcome in COVID-19 patients

The immuno-receptor Triggering Expressed on Myeloid cells-1 (TREM-1) is activated during bacterial infectious diseases, where it amplifies the inflammatory response. Small studies suggest that TREM-1 could be involved in viral infections, including COVID-19. We here aim to decipher whether plasma concentration of the soluble form of TREM-1 (sTREM-1) could predict the outcome of hospitalized COVID-19 patients.

We conducted a multicentre prospective observational study in 3 university hospitals in France. Consecutive hospitalized patients with confirmed infection with SARS-CoV-2 were enrolled. Plasma concentration of sTREM-1 was measured on admission and then at days 4, 6, 8, 14, 21, and 28 in patients admitted into an ICU (ICU cohort: ICUC) or 3 times a week for patients hospitalized in a medical ward (Conventional Cohort: ConvC). Clinical and biological data were prospectively recorded and patients were followed-up for 90 days. For medical ward patients, the outcome was deemed complicated in case of requirement of increased oxygen supply > 5 L/min, transfer to an ICU, or death. For Intensive Care Unit (ICU) patients, complicated outcome was defined by death in the ICU.

Plasma concentration of sTREM-1 at inclusion was higher in ICU patients (n = 269) than in medical ward patients (n = 562) (224 pg/mL (IQR 144-320) vs 147 pg/mL (76-249), p < 0.0001), and higher in patients with a complicated outcome in both cohorts: 178 (94-300) vs 135 pg/mL (70-220), p < 0.0001 in the ward patients, and 342 (288-532) vs 206 pg/mL (134-291), p < 0.0001 in the ICU patients. Elevated sTREM-1 baseline concentration was an independent predictor of complicated outcomes (Hazard Ratio (HR) = 1.5 (1.1-2.1), p = 0.02 in ward patients; HR = 3.8 (1.8-8.0), p = 0.0003 in ICU patients). An sTREM-1 plasma concentration of 224 pg/mL had a sensitivity of 42%, and a specificity of 76% in the ConvC for complicated outcome. In the ICUC, a 287 pg/mL cutoff had a sensitivity of 78%, and a specificity of 74% for death. The sTREM-1 concentrations increased over time in the ConvC patients with a complicated outcome (p = 0.017), but not in the ICUC patients.

In COVID-19 patients, plasma concentration of sTREM-1 is an independent predictor of the outcome, although its positive and negative likelihood ratio are not good enough to guide clinical decision as a standalone marker.