Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

The diagnosis, management and prevention of intertrigo in adults: A review

Intertrigo is a common inflammatory skin disorder caused by skin-on-skin friction in skin folds, due to moisture becoming trapped because of poor air circulation. This can occur in any area of the body where two skin surfaces are in close contact with each other. The aim of this scoping review was to systematically map, review and synthesise evidence on intertrigo in adults. We identified a wide range of evidence and performed a narrative integration of this related to the diagnosis, management and prevention of intertrigo. A literature search was conducted within the following databases: Cochrane Library, MEDLINE, CINAHL, PubMed and EMBASE. After reviewing articles for duplicates and relevance, 55 articles were included. The incorporation of intertrigo in the ICD-11 provides a clear definition and should improve the accuracy of estimates. With regards to the diagnosis, prevention and management of intertrigo, the literature demonstrates consensus among health professionals in approach and this forms the basis for the recommendations of this review: identify predisposing factors and educate patient in reducing these; educate patients in skin fold management and adopt structured skin care routine; treat secondary infection with appropriate topical agent; consider using moisture-wicking textiles within skin folds to reduce skin-on-skin friction, wick away moisture and reduce secondary infection. Overall, the quality of evidence on which to determine the strength of any recommendations for practice remains low. There remains the need for well-designed studies to test proposed interventions and build a robust evidence base. Declaration of interest: This work was supported through an unrestricted educational grant provided by Coloplast, Humlebaek, Denmark. DV, HC, FB, SM and MR participated in the Intertrigo Advisory Board supported by Coloplast, Humlebaek, Denmark. The authors have no other conflicts of interest to declare

Detection of titanium nanoparticles in the hair shafts of a patient with frontal fibrosing alopecia

International audienc

Alopécie frontale fibrosante post-ménopausique : une réaction lichénoïde aux nanoparticules de dioxyde de titane présentes dans les follicules pileux ?

International audienceL’alopécie fibrosante frontale (AFF) post-ménopausique est une pathologie émergente dont l’incidence augmente dans l’ensemble des pays. Son origine reste inconnue. Nous rapportons la présence de dioxyde de titane dans les cheveux d’une patiente atteinte d’AFF