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Biosci Rep
. 2021 Jun 25;BSR20210940.
doi: 10.1042/BSR20210940. Online ahead of print.
Increased sTREM-1 plasma concentrations are associated with poor clinical outcomes in patients with COVID-19
Aline H de Nooijer 1 , Inge Grondman 1 , Simon Lambden 2 , Emma J Kooistra 1 , Nico Af Janssen 1 , Matthijs Kox 3 , Peter Pickkers 1 , Leo Ab Joosten 1 , Frank van de Veerdonk 4 , Marc Derive 5 , Sebastien Gibot 6 , Mihai G Netea 1
Affiliations
- PMID: 34195785
- 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 focussing 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.
Keywords: acute respiratory distress syndrome (ARDS); coronavirus disease 2019 (COVID-19); inflammation; mortality; sTREM-1; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).