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The X-Linked TLR7 rs179008 T Allele Is Associated with an Increased Risk of Severe Multisystem Inflammatory Syndrome in Children/Kawasaki-like Syndrome in SARS-CoV-2-Infected Boys.

Adriana de Souza Andrade·Aline Almeida Bentes·Lilian Martins Diniz·Silvia Hees Carvalho·Erna Geessien Kroon·Marco Antonio Campos
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Abstract

The X-linked TLR7 rs179008 T allele has been associated with altered antiviral immunity. Given their shared inflammatory pathways and higher pediatric mortality rates in Brazil during the pandemic, we investigated their association with multisystem inflammatory syndrome in children (MIS-C) together with Kawasaki disease (KS) following SARS-CoV-2 infection. A cross-sectional study (2021-2022) analyzed 73 hospitalized children (<13 years) with confirmed COVID-19. Genotyping for TLR7 rs179008, TLR8 (rs3764879, rs2407992), and TLR3 rs3775291 was performed via PCR and Sanger sequencing. MIS-C/KS cases were identified using CDC criteria, with severity classified by the need for ICU care. Statistical analysis included Fisher's exact test and relative risk (RR) calculations. Hemizygous boys carrying the TLR7 T allele had a 1.87-fold higher risk of MIS-C/KS (p = 0.007) and a 1.75-fold increased risk of severe or critical outcomes. The T allele frequency was 2.6&#xd7; higher in MIS-C/KS cases versus other COVID-19 presentations. All fatalities occurred in boys (3/8 MIS-C cases) with one T-allele carrier. No associations were found for TLR8 or TLR3 variants. The TLR7 rs179008 T allele is a potential genetic risk factor for severe post-COVID-19 inflammatory syndromes in boys, likely due to impaired immune signaling. These findings highlight its utility as a biomarker for risk stratification in pediatric populations.

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HumansCOVID-19MaleSystemic Inflammatory Response SyndromeChildChild, PreschoolMucocutaneous Lymph Node SyndromeToll-Like Receptor 7AllelesSARS-CoV-2InfantGenetic Predisposition to DiseasePolymorphism, Single NucleotideCross-Sectional StudiesAdolescentFemaleGenotypeBrazilKawasaki-like syndromeTLR7rs179008 Tsevere multisystem inflammatory syndrome in childrentoll like receptorJournal Article

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Adriana de Souza Andrade, Aline Almeida Bentes, Lilian Martins Diniz, Silvia Hees Carvalho, Erna Geessien Kroon, Marco Antonio Campos. 2025-09-01. The X-Linked TLR7 rs179008 T Allele Is Associated with an Increased Risk of Severe Multisystem Inflammatory Syndrome in Children/Kawasaki-like Syndrome in SARS-CoV-2-Infected Boys.. https://doi.org/10.3390/ijms26178491

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