TY - JOUR
AU - Asano, Takaki
AU - Boisson, Bertrand
AU - Onodi, Fanny
AU - Matuozzo, Daniela
AU - Moncada-Velez, Marcela
AU - Maglorius Renkilaraj, Majistor Raj Luxman
AU - Zhang, Peng
AU - Meertens, Laurent
AU - Bolze, Alexandre
AU - Materna, Marie
AU - Korniotis, Sarantis
AU - Gervais, Adrian
AU - Talouarn, Estelle
AU - Bigio, Benedetta
AU - Seeleuthner, Yoann
AU - Bilguvar, Kaya
AU - Zhang, Yu
AU - Neehus, Anna-Lena
AU - Ogishi, Masato
AU - Pelham, Simon J.
AU - Le Voyer, Tom
AU - Rosain, Jérémie
AU - Philippot, Quentin
AU - Soler-Palacín, Pere
AU - Colobran, Roger
AU - Martin-Nalda, Andrea
AU - Rivière, Jacques G.
AU - Tandjaoui-Lambiotte, Yacine
AU - Chaïbi, Khalil
AU - Shahrooei, Mohammad
AU - Darazam, Ilad Alavi
AU - Olyaei, Nasrin Alipour
AU - Mansouri, Davood
AU - Hatipoğlu, Nevin
AU - Palabiyik, Figen
AU - Ozcelik, Tayfun
AU - Novelli, Giuseppe
AU - Novelli, Antonio
AU - Casari, Giorgio
AU - Aiuti, Alessandro
AU - Carrera, Paola
AU - Bondesan, Simone
AU - Barzaghi, Federica
AU - Rovere-Querini, Patrizia
AU - Tresoldi, Cristina
AU - Franco, Jose Luis
AU - Rojas, Julian
AU - Reyes, Luis Felipe
AU - Bustos, Ingrid G.
AU - Arias, Andres Augusto
AU - Morelle, Guillaume
AU - Kyheng, Christèle
AU - Troya, Jesús
AU - Planas-Serra, Laura
AU - Schlüter, Agatha
AU - Gut, Marta
AU - Pujol, Aurora
AU - Allende, Luis M.
AU - Rodriguez-Gallego, Carlos
AU - Flores, Carlos
AU - Cabrera-Marante, Oscar
AU - Pleguezuelo, Daniel E.
AU - Pérez de Diego, Rebeca
AU - Keles, Sevgi
AU - Aytekin, Gokhan
AU - Metin Akcan, Ozge
AU - Bryceson, Yenan T.
AU - Bergman, Peter
AU - Brodin, Petter
AU - Smole, Daniel
AU - Smith, C. I. Edvard
AU - Norlin, Anna-Carin
AU - Campbell, Tessa M.
AU - Covill, Laura E.
AU - Hammarström, Lennart
AU - Pan-Hammarström, Qiang
AU - Abolhassani, Hassan
AU - Mane, Shrikant
AU - Marr, Nico
AU - Ata, Manar
AU - Al Ali, Fatima
AU - Khan, Taushif
AU - Spaan, András N.
AU - Dalgard, Clifton L.
AU - Bonfanti, Paolo
AU - Biondi, Andrea
AU - Tubiana, Sarah
AU - Burdet, Charles
AU - Nussbaum, Robert
AU - Kahn-Kirby, Amanda
AU - Snow, Andrew L.
AU - Bustamante, Jacinta
AU - Puel, Anne
AU - Boisson-Dupuis, Stéphanie
AU - Zhang, Shen-Ying
AU - Béziat, Vivien
AU - Lifton, Richard P.
AU - Bastard, Paul
AU - Notarangelo, Luigi D.
AU - Abel, Laurent
AU - Su, Helen C.
AU - Jouanguy, Emmanuelle
AU - Amara, Ali
AU - Soumelis, Vassili
AU - Cobat, Aurélie
AU - Zhang, Qian
AU - Casanova, Jean-Laurent
AU - Covid Human Genetic Effort
AU - Covid Storm Clinicians
AU - Covid Clinicians
AU - Imagine Covid Group
AU - French Covid Cohort Study
AU - COV-Contact-Cohort
AU - Amsterdam UMC COVID-19 Biobank
AU - NIAID-USUHS Covid Study Group
PY - 2021
DA - August
TI - X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19
JO - Science Immunology
VL - 6
IS - 62
DO - https://doi.org/10.1126/sciimmunol.abl4348
AB - Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linkedTLR7variants in 16 unrelated male individuals aged 7 to 71 years (mean, 36.7 years) from a cohort of 1202 male patients aged 0.5 to 99 years (mean, 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean, 38.7 years) tested carry suchTLR7variants (P= 3.5 × 10−5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n= 2) or moderate (n= 1), severe (n= 1), or critical (n= 1) pneumonia. Two patients from a cohort of 262 male patients with severe COVID-19 pneumonia (mean, 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleteriousTLR7variants in the male general population is &lt;6.5 × 10−4. We show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-typeTLR7. The patients’ blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.
PB - American Association for the Advancement of Science
UR - https://www.research.ed.ac.uk/en/publications/fd537e41-36d1-4888-b4b4-df50340a36cf
KW - Coronavirus (COVID-19)
ER