key: cord-0960803-hruge79z authors: da Silva Neto, P. V.; de Carvalho, J. C. S.; Pimentel, V. E.; Perez, M. M.; Carmona-Garcia, I.; Neto, N. T.; Toro, D. M.; Oliveira, C. N. S.; Fraga-Silva, T. F. C.; Milanezi, C. M.; Rodrigues, L. C.; Dias, C. F. S. L.; Xavier, A. C.; Porcel, G. S.; Guarneri, I. C.; Zaparoli, K.; Garbato, C. T.; Argolo, J. G. M.; Junior, A. A. F.; de Amorim, A. P.; Degiovani, A. M.; da Silva, D. P.; Nepomuceno, D. C.; da Silva, R. C.; Constant, L. F.; Ostini, F. M.; Feitosa, M. R.; Parra, R. S.; Vilar, F. C.; Gaspar, G. G.; da Rocha, J. J. R.; Feres, O.; Barbieri, R. C. C.; Frantz, F. G.; Maruyama, S. R.; Russo, title: Prognostic value of sTREM-1 in COVID-19 patients: a biomarker for disease severity and mortality date: 2020-09-23 journal: nan DOI: 10.1101/2020.09.22.20199703 sha: cd4edc8704fca3094c9357e86f30ec5a6a248ce9 doc_id: 960803 cord_uid: hruge79z Background: The uncontrolled inflammatory response plays a critical role in the novel coronavirus disease (COVID-19) and triggering receptor expressed on myeloid cells-1 (TREM-1) is thought to be intricate to inflammatory signal amplification. This study aims to investigate the association between soluble TREM-1 (sTREM-1) and COVID-19 as a prognostic biomarker to predict the disease severity, lethality and clinical management.Methods: We enrolled 91 patients with COVID-19 in domiciliary care (44 patients) or in hospital care (47 patients), who were classified after admission into mild, moderate, severe and critical groups according to their clinical scores. As non-COVID-19 control, 30 healthy volunteers were included. Data on demographic, comorbidities and baseline clinical characteristics were obtained from their medical and nurse records. Peripheral blood samples were collected at admission and after hospitalization outcome to assess cytokine profile and sTREM-1 level by specific immunoassays Results: Within COVID-19 patients, the highest severity was associated with the most significant elevated plasma levels sTREM-1. Using receiver operating curve analysis (ROC), sTREM-1 was found to be predictive of disease severity (AUC= 0.988) and the best cut-off value for predicting in-hospital severity was [≥] 116.5 pg/mL with the sensitivity for 93.3% and specificity for 95.8%. We also described the clinical characteristics of these patients and explored the correlation with markers of the disease aggravation. The levels of sTREM-1 were positively correlated with IL-6, IL-10, blood neutrophils counts, and critical disease scoring (r= 0.68, p<0.0001). On the other hand, sTREM-1 level was significantly negative correlated with lymphocytes counting, and mild disease (r= -0.42, p<0.0001). Higher levels of sTREM-1 were related to poor outcome and death, patients who received dexamethasone tended to have lower sTREM-1 levels. Conclusion: Our results indicated that sTREM-1 in COVID-19 is associated with severe disease development and a prognostic marker for mortality. The use of severity biomarkers such as sTREM-1 together with patients clinical scores could improve the early recognition and monitoring of COVID-19 cases with higher risk of disease worsening. Key words: COVID-19; sTREM-1; Inflammation; Biomarker; Severity; Mortality. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. . https://doi.org/10.1101/2020.09.22.20199703 doi: medRxiv preprint care units, severe respiratory distress, oxygen saturation < 93% on room air and PaO2/ FiO2 < 250mmHg, need non-invasive ventilation, such as oxygen masks 172 ventilation (10-15 L/min); and iv) critical group -admission to intensive-care units, 173 acute respiratory distress syndrome, need invasive ventilation, PaO2/ FiO2 174 <200mmHg, with or without one or more additional parameters: need 175 hemodialysis, sepsis, septic shock, and multiorgan dysfunction (41) . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. R&D System, Minneapolis, USA), with a detection range of 93.8 -6,000 pg/mL. The methodology was in according to the protocol described by the manufacturer 208 (R&D Systems, Minneapolis, MN). The dependence of multiple variables: sTREM-1 release (pg/mL); oxygen 211 saturation (sO2 %); age (years); neutrophil count (x 10 9 cells/L); lymphocytes 212 count (x 10 9 cells/L); hypertension (systole); glycemia (mg/dL); male gender; 213 clinical scores (mild, moderate, severe and critical); IL-6 (pg/mL) and IL-10 214 amount (pg/mL); was calculated using Pearson correlation with cor() function in is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. . https://doi.org/10.1101/2020.09.22.20199703 doi: medRxiv preprint monocytes in the COVID-19 patients group were significant different than that in 261 the control group, while the glycemic level was significant difference between the 262 residential care and hospital care groups (Figure 1) is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. Table S2 . To further examine if higher sTREM-1 contributes to 337 disease severity, we next analyzed sTREM-1 level in COVID-19 patients 338 subgroups based on disease severity ( Figure 2B ). Despite significant differences 339 between critical and severe or moderate and to mild groups, such significance 340 was not seen for comparison between moderate and mild patients. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 23, 2020. . https://doi.org/10.1101/2020.09.22.20199703 doi: medRxiv preprint The trinity of COVID-19: 589 immunity, inflammation and intervention Dysregulation of 593 immune response in patients with COVID-19 in Wuhan Profiling serum 599 cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease 600 severity predictors C-reactive protein level 602 may predict the risk of COVID-19 aggravation Prognostic value of C-reactive 606 protein in patients with COVID-19 D-dimer as a biomarker 609 for disease severity and mortality in COVID-19 patients: A case control 610 study Innate immunity to virus infection Triggering receptor expressed on myeloid cells 1 (TREM-1) and cytokine 615 gene variants in complicated and uncomplicated malaria TREM and TREM-like receptors in inflammation 618 and disease. 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