2026-04-19T09:24:51Zhttps://recercat.cat/oai/request

oai:recercat.cat:20.500.12328/28072025-05-16T12:47:53Zcom_2072_67741col_2072_484352

00925njm 22002777a 4500 dc Solanich, Xavier author Vargas-Parra, Gardenia author Van der Made, Caspar I. author Simons, Annet author Schuurs-Hoeijmakers, Janneke author Antolí, Arnau author Del Valle, Jesús author Rocamora-Blanch, Gemma author Setién, Fernando author Esteller, Manel author Van Reijmersdal, Simon V. author Riera-Mestre, Antoni author Sabater-Riera, Joan author Capellà, Gabriel author Van de Veerdonk, Frank L. author Van der Hoven, Ben author Corbella Virós, Xavier author Hoischen, Alexander author Lázaro, Conxi author 2021 Introduction: Loss-of-function TLR7 variants have been recently reported in a small number of males to underlie strong predisposition to severe COVID-19. We aimed to determine the presence of these rare variants in young men with severe COVID-19. Methods: We prospectively studied males between 18 and 50 years-old without predisposing comorbidities that required at least high-flow nasal oxygen to treat COVID-19. The coding region of TLR7 was sequenced to assess the presence of potentially deleterious variants. Results: TLR7 missense variants were identified in two out of 14 patients (14.3%). Overall, the median age was 38 (IQR 30-45) years. Both variants were not previously reported in population control databases and were predicted to be damaging by in silico predictors. In a 30-year-old patient a maternally inherited variant [c.644A>G; p.(Asn215Ser)] was identified, co-segregating in his 27-year-old brother who also contracted severe COVID-19. A second variant [c.2797T>C; p.(Trp933Arg)] was found in a 28-year-old patient, co-segregating in his 24-year-old brother who developed mild COVID-19. Functional testing of this variant revealed decreased type I and II interferon responses in peripheral mononuclear blood cells upon stimulation with the TLR7 agonist imiquimod, confirming a loss-of-function effect. Conclusions: This study supports a rationale for the genetic screening for TLR7 variants in young men with severe COVID-19 in the absence of other relevant risk factors. A diagnosis of TLR7 deficiency could not only inform on treatment options for the patient, but also enables pre-symptomatic testing of at-risk male relatives with the possibility of instituting early preventive and therapeutic interventions. Solanich, Xavier; Vargas-Parra, Gardenia; Van der Made, Caspar I. [et al.]. Genetic screening for TLR7 variants in young and previously healthy men with severe COVID-19. Frontiers in Immunology, 2021, 12, 719115. Disponible en: <https://www.frontiersin.org/articles/10.3389/fimmu.2021.719115/full>. Fecha de acceso: 21 sep. 2021. DOI: 10.3389/fimmu.2021.719115 1664-3224 http://hdl.handle.net/20.500.12328/2807 https://dx.doi.org/10.3389/fimmu.2021.719115 COVID-19 (Malaltia) Cribratge genètic Tractament del pacient Factors de risc COVID-19 sever COVID-19 Cribado genético Tratamiento del paciente Factores de riesgo COVID-19 severo COVID-19 Genetic screening Patient treatment Risk factors COVID-19 severe Genetic screening for TLR7 variants in young and previously healthy men with severe COVID-19