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

Interactions entre les LDL (Low Density Lipoproteins) et les oestrogènes (évaluation de l'effet anti-oxydant de nouveaux dérivés)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Traitement par hormone de croissance des enfants présentant un déficit somatotrope

LYON1-BU Santé (693882101) / SudocSudocFranceF

Traitement martial dans l'anémie du post-partum (comparaison entre le fer intraveineux et le fer per os)

LYON1-BU Santé (693882101) / SudocSudocFranceF

DHA/DHAS ET GH/IGF-1 AU COURS DU VIELLISSEMENT.INTERET ET EFFICACITE D'UN TRAITEMENT SUBSTITUTIF

LYON1-BU Santé (693882101) / SudocSudocFranceF

Variations des taux d'androgènes et de cortisol au cours de six saisons chez des footballeurs professionnels

Evaluation des fonctions surrénaliennes et testiculaires chez des footballeurs professionnels en comparaison avec des sujets sédentaires, par des dosages plasmatiques des concentrations de stéroides (cortisol, sulfate de de déhydroépiandrostérone, delta-4-androstènedione, testostérone) réalisés tout au long d'une saison sportive

Variations des taux d'androgènes et de cortisol au cours de six saisons chez des footballeurs professionnels

Evaluation des fonctions surrénaliennes et testiculaires chez des footballeurs professionnels en comparaison avec des sujets sédentaires, par des dosages plasmatiques des concentrations de stéroides (cortisol, sulfate de de déhydroépiandrostérone, delta-4-androstènedione, testostérone) réalisés tout au long d'une saison sportive

Erratum to: Adult-onset Still's Disease or Systemic-Onset Juvenile Idiopathic Arthritis and Spondyloarthritis: Overlapping Syndrome or Phenotype Shift?

International audienceNo abstract availabl

One-Year Mental and Physical Health Assessment in Survivors after Extracorporeal Membrane Oxygenation for COVID-19–related Acute Respiratory Distress Syndrome

International audienceRationale: Long-term outcomes of patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome treated with extracorporeal membrane oxygenation (ECMO) are unknown. Objectives: To assess physical examination, pulmonary function tests, anxiety, depression, post-traumatic stress disorder and quality of life at 6 and 12 months after ECMO onset. Methods: Multicenter, prospective study in patients who received ECMO for COVID-19 acute respiratory distress syndrome from March to June 2020 and survived hospital discharge. Measurements and Main Results: Of 80 eligible patients, 62 were enrolled in seven French ICUs. ECMO and invasive mechanical ventilation duration were 18 (11-25) and 36 (27-62) days, respectively. All were alive, but only 19/50 (38%) returned to work and 13/42 (31%) had recovered a normal sex drive at 1 year. Pulmonary function tests were almost normal at 6 months, except for DlCO, which was still impaired at 12 months. Mental health, role-emotional, and role-physical were the most impaired domain compared with patients receiving ECMO who did not have COVID-19. One year after ICU admission, 19/43 (44%) patients had significant anxiety, 18/43 (42%) had depression symptoms, and 21/50 (42%) were at risk for post-traumatic stress disorders. Conclusions: Despite the partial recovery of the lung function tests at 1 year, the physical and psychological function of this population remains impaired. Based on the comparison with long-term follow-up of patients receiving ECMO who did not have COVID-19, poor mental and physical health may be more related to COVID-19 than to ECMO in itself, although this needs confirmation