{"entity": "publication", "iuid": "4a3d65b08c2045e5815b7c4be47b3cab", "timestamp": "2026-09-24T14:44:49.408Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4a3d65b08c2045e5815b7c4be47b3cab.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4a3d65b08c2045e5815b7c4be47b3cab"}}, "title": "X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19.", "authors": [{"family": "Asano", "given": "Takaki", "initials": "T"}, {"family": "Boisson", "given": "Bertrand", "initials": "B"}, {"family": "Onodi", "given": "Fanny", "initials": "F"}, {"family": "Matuozzo", "given": "Daniela", "initials": "D"}, {"family": "Moncada-Velez", "given": "Marcela", "initials": "M"}, {"family": "Maglorius Renkilaraj", "given": "Majistor Raj Luxman", "initials": "MRL"}, {"family": "Zhang", "given": "Peng", "initials": "P"}, {"family": "Meertens", "given": "Laurent", "initials": "L"}, {"family": "Bolze", "given": "Alexandre", "initials": "A"}, {"family": "Materna", "given": "Marie", "initials": "M"}, {"family": "Korniotis", "given": "Sarantis", "initials": "S"}, {"family": "Gervais", "given": "Adrian", "initials": "A"}, {"family": "Talouarn", "given": "Estelle", "initials": "E"}, {"family": "Bigio", "given": "Benedetta", "initials": "B"}, {"family": "Seeleuthner", "given": "Yoann", "initials": "Y"}, {"family": "Bilguvar", "given": "Kaya", "initials": "K"}, {"family": "Zhang", "given": "Yu", "initials": "Y"}, {"family": "Neehus", "given": "Anna-Lena", "initials": "AL"}, {"family": "Ogishi", "given": "Masato", "initials": "M"}, {"family": "Pelham", "given": "Simon J", "initials": "SJ"}, {"family": "Le Voyer", "given": "Tom", "initials": "T"}, {"family": "Rosain", "given": "J\u00e9r\u00e9mie", "initials": "J"}, {"family": "Philippot", "given": "Quentin", "initials": "Q"}, {"family": "Soler-Palac\u00edn", "given": "Pere", "initials": "P"}, {"family": "Colobran", "given": "Roger", "initials": "R"}, {"family": "Martin-Nalda", "given": "Andrea", "initials": "A"}, {"family": "Rivi\u00e8re", "given": "Jacques G", "initials": "JG"}, {"family": "Tandjaoui-Lambiotte", "given": "Yacine", "initials": "Y"}, {"family": "Cha\u00efbi", "given": "Khalil", "initials": "K"}, {"family": "Shahrooei", "given": "Mohammad", "initials": "M"}, {"family": "Darazam", "given": "Ilad Alavi", "initials": "IA"}, {"family": "Olyaei", "given": "Nasrin Alipour", "initials": "NA"}, {"family": "Mansouri", "given": "Davood", "initials": "D"}, {"family": "Hatipo\u011flu", "given": "Nevin", "initials": "N"}, {"family": "Palabiyik", "given": "Figen", "initials": "F"}, {"family": "Ozcelik", "given": "Tayfun", "initials": "T"}, {"family": "Novelli", "given": "Giuseppe", "initials": "G"}, {"family": "Novelli", "given": "Antonio", "initials": "A"}, {"family": "Casari", "given": "Giorgio", "initials": "G"}, {"family": "Aiuti", "given": "Alessandro", "initials": "A"}, {"family": "Carrera", "given": "Paola", "initials": "P"}, {"family": "Bondesan", "given": "Simone", "initials": "S"}, {"family": "Barzaghi", "given": "Federica", "initials": "F"}, {"family": "Rovere-Querini", "given": "Patrizia", "initials": "P"}, {"family": "Tresoldi", "given": "Cristina", "initials": "C"}, {"family": "Franco", "given": "Jose Luis", "initials": "JL"}, {"family": "Rojas", "given": "Julian", "initials": "J"}, {"family": "Reyes", "given": "Luis Felipe", "initials": "LF"}, {"family": "Bustos", "given": "Ingrid G", "initials": "IG"}, {"family": "Arias", "given": "Andres Augusto", "initials": "AA"}, {"family": "Morelle", "given": "Guillaume", "initials": "G"}, {"family": "Christ\u00e8le", "given": "Kyheng", "initials": "K"}, {"family": "Troya", "given": "Jes\u00fas", "initials": "J"}, {"family": "Planas-Serra", "given": "Laura", "initials": "L"}, {"family": "Schl\u00fcter", "given": "Agatha", "initials": "A"}, {"family": "Gut", "given": "Marta", "initials": "M"}, {"family": "Pujol", "given": "Aurora", "initials": "A"}, {"family": "Allende", "given": "Luis M", "initials": "LM"}, {"family": "Rodriguez-Gallego", "given": "Carlos", "initials": "C"}, {"family": "Flores", "given": "Carlos", "initials": "C"}, {"family": "Cabrera-Marante", "given": "Oscar", "initials": "O"}, {"family": "Pleguezuelo", "given": "Daniel E", "initials": "DE"}, {"family": "de Diego", "given": "Rebeca P\u00e9rez", "initials": "RP"}, {"family": "Keles", "given": "Sevgi", "initials": "S"}, {"family": "Aytekin", "given": "Gokhan", "initials": "G"}, {"family": "Akcan", "given": "Ozge Metin", "initials": "OM"}, {"family": "Bryceson", "given": "Yenan T", "initials": "YT"}, {"family": "Bergman", "given": "Peter", "initials": "P"}, {"family": "Brodin", "given": "Petter", "initials": "P"}, {"family": "Smole", "given": "Daniel", "initials": "D"}, {"family": "Smith", "given": "C I Edvard", "initials": "CIE"}, {"family": "Norlin", "given": "Anna-Carin", "initials": "AC"}, {"family": "Campbell", "given": "Tessa M", "initials": "TM"}, {"family": "Covill", "given": "Laura E", "initials": "LE"}, {"family": "Hammarstr\u00f6m", "given": "Lennart", "initials": "L"}, {"family": "Pan-Hammarstr\u00f6m", "given": "Qiang", "initials": "Q"}, {"family": "Abolhassani", "given": "Hassan", "initials": "H"}, {"family": "Mane", "given": "Shrikant", "initials": "S"}, {"family": "Marr", "given": "Nico", "initials": "N"}, {"family": "Ata", "given": "Manar", "initials": "M"}, {"family": "Al Ali", "given": "Fatima", "initials": "F"}, {"family": "Khan", "given": "Taushif", "initials": "T"}, {"family": "Spaan", "given": "Andr\u00e1s N", "initials": "AN"}, {"family": "Dalgard", "given": "Clifton L", "initials": "CL"}, {"family": "Bonfanti", "given": "Paolo", "initials": "P"}, {"family": "Biondi", "given": "Andrea", "initials": "A"}, {"family": "Tubiana", "given": "Sarah", "initials": "S"}, {"family": "Burdet", "given": "Charles", "initials": "C"}, {"family": "Nussbaum", "given": "Robert", "initials": "R"}, {"family": "Kahn-Kirby", "given": "Amanda", "initials": "A"}, {"family": "Snow", "given": "Andrew L", "initials": "AL"}, {"family": "COVID Human Genetic Effort", "given": "", "initials": ""}, {"family": "COVID-STORM Clinicians", "given": "", "initials": ""}, {"family": "COVID Clinicians", "given": "", "initials": ""}, {"family": "Imagine COVID Group", "given": "", "initials": ""}, {"family": "French COVID Cohort Study Group", "given": "", "initials": ""}, {"family": "CoV-Contact Cohort", "given": "", "initials": ""}, {"family": "Amsterdam UMC Covid-", "given": "", "initials": ""}, {"family": "Biobank", "given": "", "initials": ""}, {"family": "NIAID-USUHS COVID Study Group", "given": "", "initials": ""}, {"family": "Bustamante", "given": "Jacinta", "initials": "J"}, {"family": "Puel", "given": "Anne", "initials": "A"}, {"family": "Boisson-Dupuis", "given": "St\u00e9phanie", "initials": "S"}, {"family": "Zhang", "given": "Shen-Ying", "initials": "SY"}, {"family": "B\u00e9ziat", "given": "Vivien", "initials": "V"}, {"family": "Lifton", "given": "Richard P", "initials": "RP"}, {"family": "Bastard", "given": "Paul", "initials": "P"}, {"family": "Notarangelo", "given": "Luigi D", "initials": "LD"}, {"family": "Abel", "given": "Laurent", "initials": "L"}, {"family": "Su", "given": "Helen C", "initials": "HC"}, {"family": "Jouanguy", "given": "Emmanuelle", "initials": "E"}, {"family": "Amara", "given": "Ali", "initials": "A"}, {"family": "Soumelis", "given": "Vassili", "initials": "V"}, {"family": "Cobat", "given": "Aur\u00e9lie", "initials": "A"}, {"family": "Zhang", "given": "Qian", "initials": "Q"}, {"family": "Casanova", "given": "Jean-Laurent", "initials": "JL"}], "type": "journal article", "published": "2021-08-19", "journal": {"title": "Sci Immunol", "issn": "2470-9468", "volume": "6", "issue": "62", "issn-l": "2470-9468"}, "abstract": "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-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 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 such TLR7 variants (p = 3.5 \u00d7 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) 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 deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 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.", "doi": "10.1126/sciimmunol.abl4348", "pmid": "34413140", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1744435"}, {"db": "pmc", "key": "PMC8532080"}, {"db": "pii", "key": "6/62/eabl4348"}], "notes": [], "created": "2026-09-23T06:34:20.053Z", "modified": "2026-09-23T06:34:20.083Z"}