RT Journal Article
T1 Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics
A1 Gómez Carballa, Alberto
A1 Pardo Seco, Juan Pablo
A1 Pischedda, Sara
A1 Rivero Calle, Irene
A1 Butler-Laporte, Guillaume
A1 Richards, J.B.
A1 Viz Lasheras, Sandra
A1 Martinón Torres, Federico
A1 Salas Ellacuriaga, Antonio
A1 GENDRES network, 
K1 COVID-19
K1 Long-COVID-19
K1 Host
K1 TLRJ
K1 RNAseq
K1 Transcriptomics
K1 Epigenomics
K1 n-Counter
K1 DNA methylation
AB There is abundant epidemiological data indicating that the incidence of severe cases of coronavirus disease (COVID-19) is significantly higher in males than females worldwide. Moreover, genetic variation at the X-chromosome linked TLR7 gene has been associated with COVID-19 severity. It has been suggested that the sex-biased incidence of COVID-19 might be related to the fact that TLR7 escapes X-chromosome inactivation during early embryogenesis in females, thus encoding a doble dose of its gene product compared to males. We analyzed TLR7 expression in two acute phase cohorts of COVID-19 patients that used two different technological platforms, one of them in a multi-tissue context including saliva, nasal, and blood samples, and a third cohort that included different post-infection timepoints of long-COVID-19 patients. We additionally explored methylation patterns of TLR7 using epigenomic data from an independent cohort of COVID-19 patients stratified by severity and sex. In line with genome-wide association studies, we provide supportive evidence indicating that TLR7 has altered CpG methylation patterns and it is consistently downregulated in males compared to females in the most severe cases of COVID-19
PB Elsevier
YR 2022
FD 2022
LK http://hdl.handle.net/10347/29475
UL http://hdl.handle.net/10347/29475
LA eng
NO Environmental Research 215 (2022) 114288
NO This study received support from Instituto de Salud Carlos III (ISCIII): GePEM (PI16/01478/Cofinanciado FEDER; A.S.), DIAVIR (DTS19/00049/Cofinanciado FEDER, A.S.), Resvi-Omics (PI19/01039/Cofinanciado FEDER, A.S.), Agencia Gallega de Innovación (GAIN): Grupos con Potential de Crecimiento (IN607B 2020/08, A.S.); Agencia Gallega para la Gestión del Conocimiento en Salud (ACIS): BI-BACVIR (PRIS-3, A.S.), and CovidPhy (SA 304C, A.S.); ReSVinext (PI16/01569/Cofinanciado FEDER, F.M.T.), Enterogen (PI19/01090/Cofinanciado FEDER, F.M.T.) and consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CB21/06/00103; F.M.T.); GEN-COVID (IN845D 2020/23, F.M-T.) and Grupos de Referencia Competitiva (IIN607A2021/05, F.M-T). The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication
DS Minerva
RD 3 may 2026