Kurumun Atıf Alan Makalesi
Atıf Alan Yayın
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
Scopus
Open Access Toplam 1.805 atıf DOI
Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.
Atıf Kaynağı
Atıf Yapan Yayın
Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children
Scopus
Havuzumuzda Open Access 35 atıf almış
We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7–9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2–5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6–35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1–9.6]) of IFN-ω and/or IFN-α2.
Atıf Yapan Makale Bilgileri
Kurumlar (71)
Aarhus Universitet
Aarhus, Denmark
Aarhus Universitetshospital
Aarhus, Denmark
Academy of Athens
Athens, Greece
Alma Mater Studiorum Università di Bologna
Bologna, Italy
Ankara Yildirim Beyazit University
Ankara, Turkey
Bilkent Üniversitesi
Ankara, Turkey
Bursa City Hospital
Bursa, Turkey
Centre Hospitalier Universitaire de Besançon
Besancon, France
Centre Hospitalier Universitaire Ibn Rochd
Casablanca, Morocco
Centre Universitaire de Santé McGill
Montreal, Canada