Increased sTREM-1 plasma concentrations are associated with poor clinical outcomes in patients with COVID-19

• Published in: Bioscience reports Vol. 41; no. 7
• Main Authors: de Nooijer, Aline H., Grondman, Inge, Lambden, Simon, Kooistra, Emma J., Janssen, Nico A.F., Kox, Matthijs, Pickkers, Peter, Joosten, Leo A.B., van de Veerdonk, Frank L., Derive, Marc, Gibot, Sebastien, Netea, Mihai G.
• Format: Journal Article
• Language: English
• Published: New York Portland Press Ltd The Biochemical Society 01.07.2021; Portland Press Ltd
• Subjects: Biomarkers; Blood; Clinical outcomes; Coronaviruses; COVID-19; Diagnostics & Biomarkers; Host-Microbe Interactions; Illnesses; Immunology & Inflammation; Medical prognosis; Mortality; Myeloid cells; Observational studies; Patients; Plasma; R&D; Research & development; Sepsis; Severe acute respiratory syndrome coronavirus 2; Software; Survival; Survival analysis; Therapeutic targets; Translational Science; Viral diseases; Netherlands
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20210940

Abstract Patients with sepsis display increased concentrations of sTREM-1 (soluble Triggering Receptor Expressed on Myeloid cells 1), and a phase II clinical trial focusing on TREM-1 modulation is ongoing. We investigated whether sTREM-1 circulating concentrations are associated with the outcome of patients with coronavirus disease 2019 (COVID-19) to assess the role of this pathway in COVID-19. This observational study was performed in two independent cohorts of patients with COVID-19. Plasma concentrations of sTREM-1 were assessed after ICU admission (pilot cohort) or after COVID-19 diagnosis (validation cohort). Routine laboratory and clinical parameters were collected from electronic patient files. Results showed sTREM-1 plasma concentrations were significantly elevated in patients with COVID-19 (161 [129–196] pg/ml) compared to healthy controls (104 [75–124] pg/ml; P<0.001). Patients with severe COVID-19 needing ICU admission displayed even higher sTREM-1 concentrations compared to less severely ill COVID-19 patients receiving clinical ward-based care (235 [176–319] pg/ml and 195 [139–283] pg/ml, respectively, P = 0.017). In addition, higher sTREM-1 plasma concentrations were observed in patients who did not survive the infection (326 [207–445] pg/ml) compared to survivors (199 [142–278] pg/ml, P<0.001). Survival analyses indicated that patients with higher sTREM-1 concentrations are at higher risk for death (hazard ratio = 3.3, 95%CI: 1.4–7.8). In conclusion, plasma sTREM-1 concentrations are elevated in patients with COVID-19, relate to disease severity, and discriminate between survivors and non-survivors. This suggests that the TREM-1 pathway is involved in the inflammatory reaction and the disease course of COVID-19, and therefore may be considered as a therapeutic target in severely ill patients with COVID-19.