ArticleFrontiers in immunology2021
Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 76 citations in OpenAlex.
- Age modifies the association between sex and the plasma inflammatory proteome in treated HIV.The Journal of clinical investigation · 2026Trial
- Sex-based considerations in the choice for a TLR9 or TLR7/8 agonist to arm the sentinel lymph node in early-stage melanoma.Oncoimmunology · 2026Article
- Severity-dependent and sex-biased dysregulation of A-to-I RNA editing in COVID-19 reveals CTSS as a key regulatory target.RNA biology · 2026Article
- IRF7 Protects Against Severe Influenza A Infection Independently of TLR7 Recognition in Mice.Viruses · 2026Article
- Sex-Specific Association of Toll-like Receptor 8 Polymorphisms with COVID-19 Case Status in a Korean Population.Life (Basel, Switzerland) · 2026Article
- Progressive Dissociation Between Reactogenicity and Immunogenicity After Four-Dose BNT162b2 Vaccination: A 36-Month Longitudinal Study.Vaccines · 2026Article
- A biosafe mouse model for SARS-CoV-2 infection that more realistically simulates COVID-19 symptoms.Signal transduction and targeted therapy · 2026Article
- Sex hormones and gender differences in immune responses and anticancer immunity: a comprehensive review.Biologia futura · 2026Review
- Sex Differences in Lung Immunity.Immunological reviews · 2026Review
- Roles of sex and SP-A genetic variants in modulating multiorgan injuries post viral infection.Frontiers in immunology · 2026Article
- Enhanced TLR7-induced interferon responses in women living with HIV.Frontiers in immunology · 2026Article
- B cells and iBALT in TB immunity & pathogenesis.Frontiers in immunology · 2026Review
- Mechanisms and impact of long COVID: pathophysiology, neuropsychiatric effects and vaccination.Frontiers in immunology · 2026Review
- Impact of testosterone-based gender-affirming hormone therapy on toll-like receptor transcript levels and peripheral blood leukocyte counts in transmasculine individuals.Frontiers in immunology · 2026Observational
- Post-pandemic shifts in pediatric respiratory pathogens and co-infection dynamics in Xi'an and surrounding areas: a large-scale retrospective study from 2021 to 2025.BMC infectious diseases · 2025Article
- Immunogenicity of a recombinant subunit COVID-19 vaccine: A prospective, multi-centre, longitudinal study in Chinese Alzheimer's disease patients.Human vaccines & immunotherapeutics · 2025Article
- Review
- Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.Microorganisms · 2025Review
- The X-LinkedInternational journal of molecular sciences · 2025Article
- Effects of Genetic Diversity on Health Status and Parasitological Traits in a Wild Fish Population Inhabiting a Coastal Lagoon.Animals : an open access journal from MDPI · 2025Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A male sex bias has emerged in the COVID-19 pandemic, fitting to the sex-biased pattern in other viral infections. Males are 2.84 times more often admitted to the ICU and mortality is 1.39 times higher as a result of COVID-19. Various factors play a role in this, and novel studies suggest that the gene-dose of Toll-Like Receptor (TLR) 7 could contribute to the sex-skewed severity. TLR7 is one of the crucial pattern recognition receptors for SARS-CoV-2 ssRNA and the gene-dose effect is caused by X chromosome inactivation (XCI) escape. Female immune cells with TLR7 XCI escape have biallelic TLR7 expression and produce more type 1 interferon (IFN) upon TLR7 stimulation. In COVID-19, TLR7 in plasmacytoid dendritic cells is one of the pattern recognition receptors responsible for IFN production and a delayed IFN response has been associated with immunopathogenesis and mortality. Here, we provide a hypothesis that females may be protected to some extend against severe COVID-19, due to the biallelic TLR7 expression, allowing them to mount a stronger and more protective IFN response early after infection. Studies exploring COVID-19 treatment via the TLR7-mediated IFN pathway should consider this sex difference. Various factors such as age, sex hormones and escape modulation remain to be investigated concerning the TLR7 gene-dose effect.
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