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10.3389/fimmu.2021.719115

http://scihub22266oqcxt.onion/10.3389/fimmu.2021.719115
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suck abstract from ncbi


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pmid34367187      Front+Immunol 2021 ; 12 (ä): 719115
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  • Genetic Screening for TLR7 Variants in Young and Previously Healthy Men With Severe COVID-19 #MMPMID34367187
  • Solanich X; Vargas-Parra G; van der Made CI; Simons A; Schuurs-Hoeijmakers J; Antoli A; Del Valle J; Rocamora-Blanch G; Setien F; Esteller M; van Reijmersdal SV; Riera-Mestre A; Sabater-Riera J; Capella G; van de Veerdonk FL; van der Hoven B; Corbella X; Hoischen A; Lazaro C
  • Front Immunol 2021[]; 12 (ä): 719115 PMID34367187show ga
  • 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.
  • |*Mutation, Missense[MESH]
  • |*SARS-CoV-2[MESH]
  • |Adult[MESH]
  • |Amino Acid Substitution[MESH]
  • |COVID-19/*genetics/immunology/pathology[MESH]
  • |Genetic Testing[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Risk Factors[MESH]
  • |Severity of Illness Index[MESH]


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