Understanding yellow fever-associated myocardial injury: an autopsy studyResearch in context

Background: Yellow fever (YF) is a viral hemorrhagic fever, endemic in parts of South America and Africa. There is scarce evidence about the pathogenesis of the myocardial injury. The objective of this study is to evaluate the cardiac pathology in fatal cases of YF. Methods: This retrospective autop...

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Published in:EBioMedicine 2023-10, Vol.96, p.104810
Main Authors: Fernando Rabioglio Giugni, Vera Demarchi Aiello, Caroline Silverio Faria, Shahab Zaki Pour, Marielton dos Passos Cunha, Melina Valdo Giugni, Henrique Trombini Pinesi, Felipe Lourenço Ledesma, Carolina Esteves Morais, Yeh-Li Ho, Jaques Sztajnbok, Sandra de Morais Fernezlian, Luiz Fernando Ferraz da Silva, Thais Mauad, Venâncio Avancini Ferreira Alves, Paulo Hilário do Nascimento Saldiva, Leila Antonangelo, Marisa Dolhnikoff, Amaro Nunes Duarte-Neto
Format: Article
Language:English
Subjects:
17DD
Heart conduction system
Myocarditis
Vascular endothelium
YEL-AVD
Yellow fever
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Summary:Background: Yellow fever (YF) is a viral hemorrhagic fever, endemic in parts of South America and Africa. There is scarce evidence about the pathogenesis of the myocardial injury. The objective of this study is to evaluate the cardiac pathology in fatal cases of YF. Methods: This retrospective autopsy study included cases from the São Paulo (Brazil) epidemic of 2017–2019. We reviewed medical records and performed cardiac tissue histopathological evaluation, electron microscopy, immunohistochemical assays, RT-qPCR for YF virus (YFV)-RNA, and proteomics analysis on inflammatory and endothelial biomarkers. Findings: Seventy-three confirmed YF cases with a median age of 48 (34–60) years were included. We observed myocardial fibrosis in 68 (93.2%) patients; cardiomyocyte hypertrophy in 68 (93.2%); endothelial alterations in 67 (91.8%); fiber necrosis in 50 (68.5%); viral myocarditis in 9 (12.3%); and secondary myocarditis in 5 (6.8%). Four out of five patients with 17DD vaccine-associated viscerotropic disease presented with myocarditis. The cardiac conduction system showed edema, hemorrhages and endothelial fibrinoid necrosis. Immunohistochemistry detected CD68-positive inflammatory interstitial cells and YFV antigens in endothelial and inflammatory cells. YFV-RNA was detected positive in 95.7% of the cardiac samples. The proteomics analysis demonstrated that YF patients had higher levels of multiple inflammatory and endothelial biomarkers in comparison to cardiovascular controls, and higher levels of interferon gamma-induced protein 10 (IP-10) in comparison to sepsis (p = 0.01) and cardiovascular controls (p 
ISSN:2352-3964
2352-3964