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Title: Genetic Screening for TLR7 Variants in Young and Previously Healthy Men With Severe COVID-19
Author: Solanich, Xavier
Vargas Parra, Gardenía María
Van Der Made, Caspar I.
Simons, Annet
Schuurs Hoeijmakers, Janneke
Antolí, Arnau
Valle, Jesús del
Rocamora Blanch, Gemma
Setién, Fernando
Esteller, Manel
Van Reijmersdal, Simon V.
Riera Mestre, Antoni
Sabater Riera, Joan
Capellá, G. (Gabriel)
Van De Veerdonk, Frank L.
Van Der Hoven, Ben
Corbella, Xavier
Hoischen, Alexander
Lázaro García, Conxi
Keywords: COVID-19
Cribatge genètic
Genetic screening
Issue Date: 23-Jul-2021
Publisher: Frontiers Media SA
Abstract: 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.
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It is part of: Frontiers in Immunology, 2021, vol. 12, num. 719115
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Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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