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.

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-Cardiac arrest is a significant medical emergency that can occur in outpatient medical facilities. Early defibrillation has been demonstrated to be critical to an individual's survival of a cardiac arrest. The 2010 guidelines of the European Resuscitation Council advocate that defibrillators should be available throughout outpatient medical facilities, including dental offices. Nevertheless, the underwhelming amount of available data showed that dental offices were under equipped with defibrillators. Objective: The aim of this study was to assess the prevalence of defibrillation equipment in dental offices. Additionally, this assessment also surveyed non-equipped offices regarding their decisions to not have a defibrillator. Design and Subjects: We conducted a prospective study by contacting all dental offices in five randomly drawn French cities of different sizes (Paris, Besançon, Blois, Romorantin-Lanthenay and Gray). Main Results: Of the 1716 dental offices called, 1358 (79%) were joined and 24 preferred to not answer the questionnaire. Our study indicated only 41 offices (3.1%) were equipped with a defibrillator and 1212 (94%) of the dental offices lacking a defibrillator had no plans to obtain the equipment. The non-equipped practices stated that the device was expensive and not worthwhile as the primary reasons for not having defibrillation equipment. Conclusions: This study determined that despite the recommendation by the European Resuscitation Council, dental practices in France are under-equipped and reluctant to purchase defibrillation equipment. The possibility of sharing the expense of defibrillation equipment between residents and health professionals of a building and storing the device in an accessible location is suggested.Résumé -Urgence médicale au cabinet dentaire : équipement en défibrillateur des chirurgiens dentistes français. L'arrêt cardiaque est une urgence médicale pouvant survenir dans les cabinets dentaires. La défibrillation précoce est un élément critique de sa prise en charge. Les recommandations 2010 du Conseil Européen de Réanimation préconisent l'équipement de tous les cabinets de soins extrahospitaliers, donc des cabinets dentaires. Les rares études disponibles suggèrent que les cabinets dentaires sont sous-équipés. Objectif : L'objectif de cette étude est d'évaluer la prévalence des défibrillateurs dans les cabinets dentaires de plusieurs villes françaises. Nous avons également recherché les raisons expliquant l'absence d'équipement. Matériel et méthodes : Nous avons réalisé une étude prospective en contactant par téléphone tous les cabinets dentaires d'omnipratique de cinq villes françaises de différentes tailles tirées au sort (Paris, Besançon, Blois, Romorantin-Lanthenay et Gray). Résultat : Parmi les 1716 cabinets appelés, 1358 (79 %) ont pu être joints, 24 n'ont pas souhaités répondre au questionnaire. Notre étude montre que seulement 41 des cabinets dentaires contactés (3,1 %) étaient équipés d'un défibrillateur et que 1212 des cabinets non équipés (94 %) ne ...

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