TY - JOUR
T1 - Autoantibodies against type I IFNs in patients with life-threatening COVID-19
AU - Milieu Intérieur Consortium
AU - CoV-Contact Cohort
AU - Amsterdam UMC Covid-19 Biobank
AU - COVID Human Genetic Effort
AU - HGID Lab
AU - NIAID-USUHS Immune Response to COVID Group
AU - COVID Clinicians
AU - COVID-STORM Clinicians
AU - Imagine COVID Group
AU - French COVID Cohort Study Group
AU - Bastard, Paul
AU - Rosen, Lindsey B.
AU - Zhang, Qian
AU - Michailidis, Eleftherios
AU - Hoffmann, Hans Heinrich
AU - Zhang, Yu
AU - Dorgham, Karim
AU - Philippot, Quentin
AU - Rosain, Jérémie
AU - Béziat, Vivien
AU - Manry, Jérémy
AU - Shaw, Elana
AU - Haljasmägi, Liis
AU - Peterson, Pärt
AU - Lorenzo, Lazaro
AU - Bizien, Lucy
AU - Trouillet-Assant, Sophie
AU - Dobbs, Kerry
AU - de Jesus, Adriana Almeida
AU - Belot, Alexandre
AU - Kallaste, Anne
AU - Catherinot, Emilie
AU - Tandjaoui-Lambiotte, Yacine
AU - Le Pen, Jeremie
AU - Kerner, Gaspard
AU - Bigio, Benedetta
AU - Seeleuthner, Yoann
AU - Yang, Rui
AU - Bolze, Alexandre
AU - Spaan, András N.
AU - Delmonte, Ottavia M.
AU - Abers, Michael S.
AU - Aiuti, Alessandro
AU - Casari, Giorgio
AU - Lampasona, Vito
AU - Piemonti, Lorenzo
AU - Ciceri, Fabio
AU - Bilguvar, Kaya
AU - Lifton, Richard P.
AU - Vasse, Marc
AU - Smadja, David M.
AU - Migaud, Mélanie
AU - Hadjadj, Jérôme
AU - Terrier, Benjamin
AU - Duffy, Darragh
AU - Quintana-Murci, Lluis
AU - Bos, Lieuwe
AU - de Jong, Menno D.
AU - Sigaloff, Kim
AU - Thoral, Patrick
AU - van de Beek, Diederik
AU - Hovius, Joppe W. R.
AU - Schultz, Marcus J.
AU - Horn, Johanna
AU - Vlaar, Alexander P. J.
AU - Hollmann, Markus W.
AU - Hadjadj, Jérome
AU - Roussel, Lucie
AU - Vinh, Donald C.
AU - Stilma, Willemke
N1 - Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anna Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, Osoul Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus W. Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno D. de Jong12, Rutger Koning4, Niels van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Benedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus J. Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P. J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek18*
PY - 2020/10/23
Y1 - 2020/10/23
N2 - Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
AB - Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
UR - http://www.scopus.com/inward/record.url?scp=85094096675&partnerID=8YFLogxK
U2 - https://doi.org/10.1126/science.abd4585
DO - https://doi.org/10.1126/science.abd4585
M3 - Article
C2 - 32972996
SN - 0036-8075
VL - 370
JO - Science
JF - Science
IS - 6515
M1 - eabd4585
ER -