Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

COVID Clinicians; GEN-COVID Study Group; COVID Human Genetic Effort

doi:10.1084/jem.20231353

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

COVID Clinicians
, GEN-COVID Study Group
, COVID Human Genetic Effort

Graduate Institute of Immunology and Translational Medicine

Université Paris Cité
Rockefeller University
Paris Cité University
Hiroshima University
University of Tartu
Vall d'Hebron Research Institute
S. Orsola-Malpighi University Hospital
University of Bologna
National Reference Center for Rheumatic
Hospices civils de Lyon
École normale supérieure de Lyon
Université de Lyon
Institute of Science Tokyo
Ghent University
Goce Delčev University of Štip
Institute of Public Health of the Republic of North Macedonia
Bilkent University
Necmettin Erbakan University
Saint Denis Hospital
INSERM UMR 1137 IAME
Universite Sorbonne Paris Nord
Karolinska Institutet
Tehran University of Medical Sciences
Innsbruck Medical University
National and Kapodistrian University of Athens
Bellvitge Biomedical Research Institute
Generalitat de Catalunya
CIBERER-ISCIII
Hospital Universitario Infanta Leonor
University of Management and Technology
KU Leuven
McGill University
University of Copenhagen
Faculdades Pequeno Príncipe

Research output: Contribution to journal › Journal Article › peer-review

29 Scopus citations

Abstract

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.

Original language	English
Article number	e20231353
Journal	Journal of Experimental Medicine
Volume	221
Issue number	2
DOIs	https://doi.org/10.1084/jem.20231353
State	Published - 01 01 2024

Bibliographical note

Publisher Copyright:
© 2024, Rockefeller University Press. All rights reserved.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

COVID-19
Immunodeficiency
Infectious disease and host defense
Innate immunity and inflammation

Access to Document

10.1084/jem.20231353

Cite this

@article{f4d0255086e846d9b456133058c45209,

title = "Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children",

abstract = "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.",

keywords = "COVID-19, Immunodeficiency, Infectious disease and host defense, Innate immunity and inflammation",

author = "\{COVID Clinicians\} and \{GEN-COVID Study Group\} and \{COVID Human Genetic Effort\} and Paul Bastard and Adrian Gervais and Maki Taniguchi and Liisa Saare and Karita S{\"a}rekannu and Voyer, \{Tom Le\} and Quentin Philippot and J{\'e}r{\'e}mie Rosain and Lucy Bizien and Takaki Asano and Marina Garcia-Prat and Alba Parra-Mart{\'i}nez and M{\'e}lanie Migaud and Miyuki Tsumura and Francesca Conti and Alexandre Belot and Rivi{\`e}re, \{Jacques G.\} and Tomohiro Morio and Junko Tanaka and Etienne Javouhey and Filomeen Haerynck and Sotirija Duvlis and Tayfun Ozcelik and Sevgi Keles and Yacine Tandjaoui-Lambiotte and Simon Escoda and Maya Husain and Qiang Pan-Hammarstr{\"o}m and Lennart Hammarstr{\"o}m and Gloria Ahlijah and Haidar, \{Anthony Abi\} and Camille Soudee and Vincent Arseguel and Hassan Abolhassani and Sabina Sahanic and Ivan Tancevski and Yoko Nukui and Seiichi Hayakawa and Chrousos, \{George P.\} and Athanasios Michos and Tatsi, \{Elizabeth Barbara\} and Filippos Filippatos and Agusti Rodriguez-Palmero and Jesus Troya and Imran Tipu and Isabelle Meyts and Lucie Roussel and Ostrowski, \{Sisse Rye\} and Laire Schidlowski and Ku, \{Cheng Lung\}",

year = "2024",

month = jan,

day = "1",

doi = "10.1084/jem.20231353",

language = "英语",

volume = "221",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "2",

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TY - JOUR

T1 - Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

AU - COVID Clinicians

AU - GEN-COVID Study Group

AU - COVID Human Genetic Effort

AU - Bastard, Paul

AU - Gervais, Adrian

AU - Taniguchi, Maki

AU - Saare, Liisa

AU - Särekannu, Karita

AU - Voyer, Tom Le

AU - Philippot, Quentin

AU - Rosain, Jérémie

AU - Bizien, Lucy

AU - Asano, Takaki

AU - Garcia-Prat, Marina

AU - Parra-Martínez, Alba

AU - Migaud, Mélanie

AU - Tsumura, Miyuki

AU - Conti, Francesca

AU - Belot, Alexandre

AU - Rivière, Jacques G.

AU - Morio, Tomohiro

AU - Tanaka, Junko

AU - Javouhey, Etienne

AU - Haerynck, Filomeen

AU - Duvlis, Sotirija

AU - Ozcelik, Tayfun

AU - Keles, Sevgi

AU - Tandjaoui-Lambiotte, Yacine

AU - Escoda, Simon

AU - Husain, Maya

AU - Pan-Hammarström, Qiang

AU - Hammarström, Lennart

AU - Ahlijah, Gloria

AU - Haidar, Anthony Abi

AU - Soudee, Camille

AU - Arseguel, Vincent

AU - Abolhassani, Hassan

AU - Sahanic, Sabina

AU - Tancevski, Ivan

AU - Nukui, Yoko

AU - Hayakawa, Seiichi

AU - Chrousos, George P.

AU - Michos, Athanasios

AU - Tatsi, Elizabeth Barbara

AU - Filippatos, Filippos

AU - Rodriguez-Palmero, Agusti

AU - Troya, Jesus

AU - Tipu, Imran

AU - Meyts, Isabelle

AU - Roussel, Lucie

AU - Ostrowski, Sisse Rye

AU - Schidlowski, Laire

AU - Ku, Cheng Lung

PY - 2024/1/1

Y1 - 2024/1/1

N2 - 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.

AB - 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.

KW - COVID-19

KW - Immunodeficiency

KW - Infectious disease and host defense

KW - Innate immunity and inflammation

UR - https://www.scopus.com/pages/publications/85181628485

U2 - 10.1084/jem.20231353

DO - 10.1084/jem.20231353

M3 - 文章

C2 - 38175961

AN - SCOPUS:85181628485

SN - 0022-1007

VL - 221

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 2

M1 - e20231353

ER -

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

Abstract

Bibliographical note

UN SDGs

Keywords

Access to Document

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