Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/222239
Title: From Rare to Common: Genetic Insights into TLR7 Variants in a Multicentric Spanish Study on COVID-19 Severity
Author: Antolí, Arnau
Vargas Parra, Gardenía María
Sierra Fortuny, Àngels
Gómez Vázquez, José Luis
Rofes, Paula
Munté, Elisabet
Viana Errasti, Julen
Marín Montes, Raúl
López Dóriga Guerra, Adriana
Feliubadaló, Lidia
Valle, Jesús del
Pérez González, Alexandre
Poveda, Eva
Solanich, Xavier
Lázaro García, Conxi
Keywords: SARS-CoV-2
Epidemiologia genètica
SARS-CoV-2
Genetic epidemiology
Issue Date: 27-May-2025
Publisher: Springer Science and Business Media LLC
Abstract: TLR7, which encodes a key receptor for single-stranded RNA (ssRNA) virus of the innate immune system, was recently associated with X-linked immunodeficiency and COVID-19 susceptibility. This study investigates the association between TLR7 variants and susceptibility to severe COVID-19 in a multicentric Spanish cohort. The TLR7 gene was sequenced in a cohort of 365 COVID-19 patients, stratified into two groups: one comprising mild and asymptomatic patients, considered as controls (n = 87), and the other consisting of moderate to severely affected patients hospitalized due to COVID-19 pneumonia, considered as cases (n = 278). A total of 152 unique TLR7 variants were identified, of note, six rare variants were identified in 11 cases (3.96%), all of whom belonged to the case group. The functional impact of rare TLR7 variants was assessed using a luciferase reporter assay and revealed that N215S is a loss-of-function (LOF) variant, while D332G exhibits an hypomorphic behavior. Conversely, H90Y, V219I, A448V, and R902K maintained normal signaling. No skewed X-inactivation was observed in female carriers of N215S or D332G. In addition, the common variants Q11L (rs179008), c.4-151A>G (rs179009) and c.*881C>G (rs3853839) were associated with severe pneumonia, while c.4-151A>G (rs179009) was specifically linked to Intensive Care Unit (ICU) admission. These findings highlight the role of TLR7 in antiviral immune response and its association with severe COVID-19 in men. The luciferase assay proves to be a reliable tool for evaluating TLR7 signaling, effectively distinguishing between neutral, LOF, and gain-of-function (GOF) variants. Further research is needed to better understand TLR7 variants and its implications in immunodeficiency and immune dysregulation.
Note: Reproducció del document publicat a: https://doi.org/10.1007/s10875-025-01892-0
It is part of: Journal of Clinical Immunology, 2025, vol. 45, num. 1, 100
URI: https://hdl.handle.net/2445/222239
Related resource: https://doi.org/10.1007/s10875-025-01892-0
ISSN: 1573-2592
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Clíniques)

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