Circulating sTREM-1 as a predictive biomarker of pediatric multisystemic inflammatory syndrome (MIS-C)

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Goncalves, Guilherme S. ; Correa-Silva, Simone ; Zheng, Yingying ; Avelar, Isabela ; Montenegro, Marilia M. ; Ferreira, Arthur E. F. ; Bain, Vera ; Fink, Thais T. ; Suguita, Priscila ; Astley, Camilla ; Lindoso, Livia ; Martins, Fernanda ; Matsuo, Olivia M. ; Ferreira, Juliana C. O. A. ; Firigato, Isabela ; Goncalves, Fernanda de Toledo ; Pereira, Maria Fernanda B. ; da Silva, Clovis Artur A. ; Carneiro-Sampaio, Magda ; Marques, Heloisa H. S. ; Palmeira, Patricia

• Document type: Journal article
• Source: CYTOKINE; v. 161, p. 12-pg., 2023-01-01.

Abstract

The exacerbation of the inflammatory response caused by SARS-CoV-2 in adults promotes the production of soluble mediators that could act as diagnostic and prognostic biomarkers for COVID-19. Among the potential biomarkers, the soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) has been described as a predictor of inflammation severity. The aim was to evaluate sTREM-1 and cytokine serum concentrations in pediatric patients during the acute and convalescent phases of COVID-19. This was a prospective study that included 53 children/adolescents with acute COVID-19 (Acute-CoV group); 54 who recovered from COVID-19 (Post-CoV group) and 54 controls (Control group). Preexisting chronic conditions were present in the three groups, which were defined as follows: immunological diseases, neurological disorders, and renal and hepatic failures. The three groups were matched by age, sex, and similar preexisting chronic conditions. No differences in sTREM-1 levels were detected among the groups or when the groups were separately analyzed by preexisting chronic conditions. However, sTREM-1 analysis in the seven multisystemic inflammatory syndrome children (MIS-C) within the Acute-Cov group showed that sTREM-1 concentrations were higher in MIS-C vs non-MIS-C acute patients. Then, the receiver operating curve analysis (ROC) performed with MIS-C acute patients revealed a significant AUC of 0.870, and the sTREM-1 cutoff value of > 5781 pg/mL yielded a sensitivity of 71.4 % and a specificity of 91.3 % for disease severity, and patients with sTREM-1 levels above this cutoff presented an elevated risk for MIS-C development in 22.85-fold (OR = 22.85 [95 % CI 1.64-317.5], p = 0.02). The cytokine analyses in the acute phase revealed that IL-6, IL-8, and IL-10 concentrations were elevated regardless of whether the patient developed MIS-C, and those levels decreased in the convalescent phase, even when compared with controls. Spearman correlation analysis generated positive indexes between sTREM-1 and IL-12 and TNF-alpha concentrations, only within the Acute-CoV group. Our findings revealed that sTREM-1 in pediatric patients has good predictive accuracy as an early screening tool for surveillance of MIS-C cases, even in patients with chronic underlying conditions. (AU)

• FAPESP's process: 16/06887-5 - STUDY OF PROTEIN BIOMARKERS AND GENE EXPRESSION PROFILE OF NF-˜B PATHWAY IN LATE-ONSET NEONATAL SEPSIS: POTENTIAL VALUE IN DIAGNOSIS AND PROGNOSIS
• Grantee: Patricia Palmeira Daenekas Jorge
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/03037-9 - Assessment of soluble TREM-1 levels in pediatric patients with COVID-19 and post-infection with the SARS-COV-2 virus treated at HC-FMUSP
• Grantee: Guilherme de Souza Gonçalves
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 14/50489-9 - Human thymus: development and diseases
• Grantee: Magda Maria Sales Carneiro-Sampaio
• Support Opportunities: Research Projects - Thematic Grants