Session Type: ePosters
Session Title: ePosters
Authors(s): A.H. De Nooijer (1, 2), I. Grondman (1, 2), S. Lambden (3), E.J. Kooistra (4, 2), N.A.F. Janssen (1, 2), M. Kox (4, 2), P. Pickkers (4, 2), L.A.B. Joosten (1, 2, 5), F.L. Van De Veerdonk (1, 2), M. Derive (6), S. Gibot (7), M.G. Netea (1, 2, 8)
Authors Affiliations(s): (1) Department of Internal Medicine, Radboud University Medical Centre, Netherlands, (2) Radboud Centre for Infectious Diseases, Netherlands, (3) Department of Medicine, University of Cambridge, United Kingdom, (4) Department of Intensive Care Medicine, Radboud University Medical Centre, Netherlands, (5) Núcleo de Pesquisa da Faculdade da Polícia Militar do Estado de Goiás, Brazil, (6) Inotrem, France, (7) Intensive Care Unit, Centre Hospitalier Regional Universitaire, France, (8) Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, Germany
Third Party Affiliation: RCI-COVID-19 study group
Background:
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 the sTREM-1 concentrations are associated with the outcome of patients with coronavirus disease 2019 (COVID-19), suggesting that TREM-1 is a potential therapeutic target.
Methods:This observational study was performed in two independent cohorts: a pilot cohort of 21 healthy volunteers and 24 patients with COVID-19 admitted to the ICU of Centre Hospitalier Régional Universitaire de Nancy, France, and a validation cohort of 192 patients with COVID-19 (both ICU and non-ICU) admitted to the Radboud University Medical Centre (Radboudumc), Nijmegen, the Netherlands. Plasma concentrations of sTREM-1 were measured using enzyme-linked immunosorbent assays (ELISA, Quantikine, R&D systems) after ICU admission (pilot cohort) or after COVID-19 diagnosis (validation cohort). Routine clinical and laboratory parameters were collected from electronic patient files.
Results: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; Figure 1a). 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; Figure 1b). 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; Figure 1c). Receiver operating characteristic (ROC) analyses showed that the discriminatory power of sTREM-1 (AUC=0.73, 95%CI 0.62-0.83) was similar to that of IL-6 (AUC=0.77, 95%CI 0.65-0.88; p=0.887), but performed better than CRP (AUC=0.59, 95%CI 0.47-0.71; p=0.132) and ferritin (AUC=0.58, 95%CI 0.46-0.70; p=0.078), although not significantly different (Figure 2). 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; Figure 3).
Conclusions:
In patients with COVID-19, plasma sTREM-1 concentrations are elevated, 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 COVID-19 disease course, and therefore may act as a potential therapeutic target in severely ill patients with COVID-19.
Keyword(s): COVID-19, sTREM-1, InflammationCOI Other: MD and SG are founders of Inotrem, and MD and SL are employees of Inotrem SA, a company developing TREM-1 targeting therapies. The other authors declare no conflict of interest or competing interest.
Session Type: ePosters
Session Title: ePosters
Authors(s): A.H. De Nooijer (1, 2), I. Grondman (1, 2), S. Lambden (3), E.J. Kooistra (4, 2), N.A.F. Janssen (1, 2), M. Kox (4, 2), P. Pickkers (4, 2), L.A.B. Joosten (1, 2, 5), F.L. Van De Veerdonk (1, 2), M. Derive (6), S. Gibot (7), M.G. Netea (1, 2, 8)
Authors Affiliations(s): (1) Department of Internal Medicine, Radboud University Medical Centre, Netherlands, (2) Radboud Centre for Infectious Diseases, Netherlands, (3) Department of Medicine, University of Cambridge, United Kingdom, (4) Department of Intensive Care Medicine, Radboud University Medical Centre, Netherlands, (5) Núcleo de Pesquisa da Faculdade da Polícia Militar do Estado de Goiás, Brazil, (6) Inotrem, France, (7) Intensive Care Unit, Centre Hospitalier Regional Universitaire, France, (8) Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, Germany
Third Party Affiliation: RCI-COVID-19 study group
Background:
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 the sTREM-1 concentrations are associated with the outcome of patients with coronavirus disease 2019 (COVID-19), suggesting that TREM-1 is a potential therapeutic target.
Methods:This observational study was performed in two independent cohorts: a pilot cohort of 21 healthy volunteers and 24 patients with COVID-19 admitted to the ICU of Centre Hospitalier Régional Universitaire de Nancy, France, and a validation cohort of 192 patients with COVID-19 (both ICU and non-ICU) admitted to the Radboud University Medical Centre (Radboudumc), Nijmegen, the Netherlands. Plasma concentrations of sTREM-1 were measured using enzyme-linked immunosorbent assays (ELISA, Quantikine, R&D systems) after ICU admission (pilot cohort) or after COVID-19 diagnosis (validation cohort). Routine clinical and laboratory parameters were collected from electronic patient files.
Results: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; Figure 1a). 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; Figure 1b). 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; Figure 1c). Receiver operating characteristic (ROC) analyses showed that the discriminatory power of sTREM-1 (AUC=0.73, 95%CI 0.62-0.83) was similar to that of IL-6 (AUC=0.77, 95%CI 0.65-0.88; p=0.887), but performed better than CRP (AUC=0.59, 95%CI 0.47-0.71; p=0.132) and ferritin (AUC=0.58, 95%CI 0.46-0.70; p=0.078), although not significantly different (Figure 2). 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; Figure 3).
Conclusions:
In patients with COVID-19, plasma sTREM-1 concentrations are elevated, 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 COVID-19 disease course, and therefore may act as a potential therapeutic target in severely ill patients with COVID-19.
Keyword(s): COVID-19, sTREM-1, InflammationCOI Other: MD and SG are founders of Inotrem, and MD and SL are employees of Inotrem SA, a company developing TREM-1 targeting therapies. The other authors declare no conflict of interest or competing interest.