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

A new model for transfer line with simultaneous activation of multi-spindle heads at workstations

6 pages, CD-ROMInternational audienc

Preparation and physical properties of the layered niobate Cu0.5Nb3O8 : application to photocatalytic hydrogen evolution

Journal of Statistical Computation and Simulation713201-21

Un programme linéaire pour la conception des lignes de transfert à partir d'un ensemble fixe de têtes d'usinage

International audienc

Synergistic effect of human Bone Morphogenic Protein-2 and Mesenchymal Stromal Cells on chronic wounds through hypoxia-inducible factor-1 α induction

International audienceChronic skin ulcers and burns require advanced treatments. Mesenchymal Stromal Cells (MSCs) are effective in treating these pathologies. Bone Morphogenic Protein-2 (BMP-2) is known to enhance angiogenesis. We investigated whether recombinant human hBMP-2 potentiates the effect of MSCs on wound healing. Severe ulceration was induced in rats by irradiation and treated by co-infusion of MSCs with hBMP-2 into the ulcerated area which accelerated wound healing. Potentiation of the effect of MSCs by hBMP-2 on endothelial repair improved skin healing. HBMP-2 and MSCs synergistically, in a supra additive or enhanced manner, renewed tissue structures, resulting in normalization of the epidermis, hair follicles, sebaceous glands, collagen fibre density, and blood vessels. Co-localization of MSCs with CD31 + cells suggests recruitment of endothelial cells at the site of injection. HBMP-2 and MSCs enhanced angiogenesis and induced micro-vessel formation in the dermis where hair follicles were regenerated. HBMP-2 acts by causing hypoxia-inducible factor-1 α (HIF-1α) expression which impacts endothelial tube formation and skin repair. This effect is abolished by siRNA. These results propose that new strategies adding cytokines to MSCs should be evaluated for treating radiation-induced dermatitis, burns, and chronic ulcers in humans. © 2017 The Author(s)

Effect of polyethylene cover on the treatment of exposure keratopathy in ICU

Background Exposure keratopathy may lead to serious complications such as microbial keratitis, corneal perforation, and visual impairment if not treated. Aim To compare the effect of carbomer eye drops when used alone and in combination with polyethylene covers in the healing of exposure keratopathy. Methods A single blind randomized-controlled trial (RCT) in two intensive care units (ICUs) was carried out in a university hospital in Western Turkey between September 2011 and December 2012.The control group received only carbomer, eye drops while the intervention group received both carbomer eye drops and polyethylene covers. the primary outcome was the decrease or absence of corneal damage, which refers to healing. Corneal damage was followed up with a fluorescein dye test (decrease/absence of the corneal staining) by the same ophthalmologist for 10 days. Results A total of 43 corneas in 24 patients were studied. Corneal epithelial defects decreased in the intervention group by day 2 and progressed or remained unchanged in the control group every day (P= .001). Patient characteristics did not affect the grade ranges of corneal staining in the groups except for level of consciousness. Conclusion Carbomer eye drops, when used in combination with polyethylene covers, were effective in managing exposure keratopathy. Relevance to clinical practice Corneal damage and further ocular complications can be reduced with the utilization of polyethylene covers in nursing care and treatment.Devlet Planlama Orgutu [05-DPT-003/22]Devlet Planlama Orgutu, Grant/Award Number: 05-DPT-003/2