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

Les plastiques et la culture du champignon de couche

Economic data on Paris mushrooms. Use of plastics at two levels: for compost conditioning and for pre-fructification with the placement of a film on the rendering soil. / Données économiques sur le champignon de Paris. Utilisation des plastiques à deux niveaux : pour le conditionnement du compost et pour la pré-fructification avec le placement d'un film sur la terre de gobetage

L'utilisation des produits phytosanitaires en champignonnieres : une attitude reflechie et responsable.

National audienc

Discussions on assessment of artificial infections with Verticillium fungicola for breeding programmes

International audienc

Le confetti est de retour

National audienc

Optimum measure of cap color in Agaricus bisporus wild and cultivated strains

International audienc

Programme d'amélioration génétique du champignon de Paris

National audienc

Varietal and technical innovations for the sustainable and integrated management of root-knot nematodes

International audienceThe current restrictions on the use of chemical nematicides have contributed to increased root-knot nematodes (Meloidogyne spp.) problems in horticultural crops. In this context, plant resistance (R) appears as the most effective method of control, but the restricted number of cultivated vegetable species with root-knot nematode R-genes available (tomato, pepper), and the possible occurrence of virulent nematodes able to reproduce on R-plants may constitute a severe threat to this control strategy. To increase the sustainability of the protection, a scientific challenge exists in building cropping strategies based on the combination of genetic resistance with cultivation practices. Our projects aimed at assessing such innovative strategies in a multi-site device in research stations and commercial farms. First, we looked at three components of crop protection, i.e., R-efficiency, R-durability, and sustainability of rotating cultivation. Overall, a constant hierarchy of management strategies was observed, with Pyramyding > Alternating > Mixture of R-genes > Sequential use of a single R-gene introgressed in a susceptible background. We are currently analysing (1) the impact of agronomic practices on the parasite pressure in the soil and on ecological diversity including other nematode species, (2) the linkage between reduction of Meloidogyne populations in the soil and increase of R-genes durability, and (3) the sustainability assessment of such varietal and technical innovations. Multidisciplinary approaches were combined to foster synergistic and long-term goals. The diversity of partners and associated forces brought all the complementary expertise needed for answering specific short-term questions as well as generic mid- to long-term expectations