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. 2025 Oct;91(4):106613.
doi: 10.1016/j.jinf.2025.106613. Epub 2025 Sep 12.

Small-RNA sequencing identifies serum microRNAs associated with abnormal electrocardiography findings in patients with Chagas disease

Michael Mueller  1 , Alice Blandino  2 , Dominique Scherer  2 , Inés Zulantay  3 , Werner Apt  3 , Nelson M Varela  4 , Marcelo Llancaqueo  5 , Lineth Garcia  6 , Lourdes Ortiz  7 , Emanuele Nicastri  8 , Maria Letizia Giancola  8 , Andrea Angheben  9 , Simona Gabrielli  10 , Trine B Rounge  11 , Hilde Langseth  12 , Melanie Waldenberger  13 , Pamela Salinas-Alvarez  14 , Justo Lorenzo Bermejo  15
Affiliations
Free article

Small-RNA sequencing identifies serum microRNAs associated with abnormal electrocardiography findings in patients with Chagas disease

Michael Mueller et al. J Infect. 2025 Oct.
Free article

Abstract

Background: Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), affects around 6-7 million people in Latin America and hundreds of thousands in the United States and Europe. A main complication of chronic Chagas disease is cardiomyopathy, possibly manifesting as arrhythmias, heart failure, or sudden cardiac death. Understanding the link between T. cruzi infection and cardiomyopathy is essential for early diagnosis and adequate treatment.

Methods: We sequenced small RNAs in serum samples from 228 Chagas patients recruited in Chile, Bolivia and Italy. After bioinformatic processing of sequencing data to quantify serum miRNA expression, robust logistic regression was applied to identify miRNAs differentially expressed in Chagas patients with abnormalities in electrocardiography (ECG), bundle-branch block on ECG, and high Kuschnir scores. We also investigated the association between genotype-based miRNA expression and the risk of abnormal ECG findings.

Findings: As reported, the risk of abnormal ECG findings was higher in male patients and increased with age. Three miRNAs showed lower serum expression levels in patients with abnormal ECG: miRNA-101-3p, miRNA-576-3p and miRNA-629-5p (p < 0.0002), especially in patients with high Kuschnir scores. The expression of miRNA-629-5p was negatively correlated with the CCL5 expression (p = 3.7×10-8), a chemokine frequently reported in Chagas disease. Gene enrichment analyses indicated involvement of cytokine signalling in Chagas cardiomyopathy.

Interpretation: The findings demonstrate the potential of circulating miRNAs as diagnostic biomarkers for Chagas cardiomyopathy. The associations found with disease severity and immune response may help to improve our knowledge of complications' development in Chagas disease.

Keywords: Biomarkers; C-C motif chemokine ligand 5 (CCL5); Cardiomyopathy; Chagas; MicroRNA; Small-RNA sequencing.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.