IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34895-1.html
   My bibliography  Save this article

Defective activation and regulation of type I interferon immunity is associated with increasing COVID-19 severity

Author

Listed:
  • Nikaïa Smith

    (Université Paris Cité)

  • Céline Possémé

    (Université Paris Cité)

  • Vincent Bondet

    (Université Paris Cité)

  • Jamie Sugrue

    (Trinity College Dublin)

  • Liam Townsend

    (Trinity College Dublin
    St James’s Hospital)

  • Bruno Charbit

    (Center for Translational Research)

  • Vincent Rouilly

    (Datactix)

  • Violaine Saint-André

    (Université Paris Cité
    Institut Pasteur)

  • Tom Dott

    (Center for Translational Research)

  • Andre Rodriguez Pozo

    (Université Paris Cité)

  • Nader Yatim

    (Université Paris Cité)

  • Olivier Schwartz

    (Institut Pasteur)

  • Minerva Cervantes-Gonzalez

    (AP-HP, Hôpital Bichat
    AP-HP, Hôpital Bichat
    IAME)

  • Jade Ghosn

    (AP-HP, Hôpital Bichat
    IAME)

  • Paul Bastard

    (Necker Hospital for Sick Children, AP-HP
    Necker Hospital for Sick Children
    Imagine Institute
    The Rockefeller University)

  • Jean Laurent Casanova

    (Necker Hospital for Sick Children, AP-HP
    Necker Hospital for Sick Children
    Imagine Institute
    The Rockefeller University)

  • Tali-Anne Szwebel

    (APHP)

  • Benjamin Terrier

    (APHP)

  • Niall Conlon

    (St James’s Hospital
    Trinity College Dublin)

  • Cliona O’Farrelly

    (Trinity College Dublin
    Trinity College Dublin)

  • Clíona Ní Cheallaigh

    (Trinity College Dublin
    St James’s Hospital)

  • Nollaig M. Bourke

    (Trinity College Dublin)

  • Darragh Duffy

    (Université Paris Cité
    Center for Translational Research)

Abstract

Host immunity to infection with SARS-CoV-2 is highly variable, dictating diverse clinical outcomes ranging from asymptomatic to severe disease and death. We previously reported reduced type I interferon in severe COVID-19 patients preceded clinical worsening. Further studies identified genetic mutations in loci of the TLR3- or TLR7-dependent interferon-I pathways, or neutralizing interferon-I autoantibodies as risk factors for development of COVID-19 pneumonia. Here we show in patient cohorts with different severities of COVID-19, that baseline plasma interferon α measures differ according to the immunoassay used, timing of sampling, the interferon α subtype measured, and the presence of autoantibodies. We also show a consistently reduced induction of interferon-I proteins in hospitalized COVID-19 patients upon immune stimulation, that is not associated with detectable neutralizing autoantibodies against interferon α or interferon ω. Intracellular proteomic analysis shows increased monocyte numbers in hospitalized COVID-19 patients but impaired interferon-I response after stimulation. We confirm this by ex vivo whole blood stimulation with interferon-I which induces transcriptomic responses associated with inflammation in hospitalized COVID-19 patients, that is not seen in controls or non-hospitalized moderate cases. These results may explain the dichotomy of the poor clinical response to interferon-I based treatments in late stage COVID-19, despite the importance of interferon-I in early acute infection and may guide alternative therapeutic strategies.

Suggested Citation

  • Nikaïa Smith & Céline Possémé & Vincent Bondet & Jamie Sugrue & Liam Townsend & Bruno Charbit & Vincent Rouilly & Violaine Saint-André & Tom Dott & Andre Rodriguez Pozo & Nader Yatim & Olivier Schwart, 2022. "Defective activation and regulation of type I interferon immunity is associated with increasing COVID-19 severity," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34895-1
    DOI: 10.1038/s41467-022-34895-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34895-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-34895-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Qian Zhang & Paul Bastard & Aurélie Cobat & Jean-Laurent Casanova, 2022. "Human genetic and immunological determinants of critical COVID-19 pneumonia," Nature, Nature, vol. 603(7902), pages 587-598, March.
    2. Carolina Lucas & Patrick Wong & Jon Klein & Tiago B. R. Castro & Julio Silva & Maria Sundaram & Mallory K. Ellingson & Tianyang Mao & Ji Eun Oh & Benjamin Israelow & Takehiro Takahashi & Maria Tokuyam, 2020. "Longitudinal analyses reveal immunological misfiring in severe COVID-19," Nature, Nature, vol. 584(7821), pages 463-469, August.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Tristram A. J. Ryan & Alexander Hooftman & Aisling M. Rehill & Matt D. Johansen & Eóin C. O’ Brien & Juliana E. Toller-Kawahisa & Mieszko M. Wilk & Emily A. Day & Hauke J. Weiss & Pourya Sarvari & Emi, 2023. "Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress Tissue Factor in macrophages via inhibition of Type I Interferon," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Wei Feng & Joanne C. Beer & Qinyu Hao & Ishara S. Ariyapala & Aparna Sahajan & Andrei Komarov & Katie Cha & Mason Moua & Xiaolei Qiu & Xiaomei Xu & Shweta Iyengar & Thu Yoshimura & Rajini Nagaraj & Li, 2023. "NULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Shelly J. Robertson & Olivia Bedard & Kristin L. McNally & Carl Shaia & Chad S. Clancy & Matthew Lewis & Rebecca M. Broeckel & Abhilash I. Chiramel & Jeffrey G. Shannon & Gail L. Sturdevant & Rebecca , 2023. "Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Kim McFann & Bridget A. Baxter & Stephanie M. LaVergne & Sophia Stromberg & Kailey Berry & Madison Tipton & Jared Haberman & Jeremy Ladd & Tracy L. Webb & Julie A. Dunn & Elizabeth P. Ryan, 2021. "Quality of Life (QoL) Is Reduced in Those with Severe COVID-19 Disease, Post-Acute Sequelae of COVID-19, and Hospitalization in United States Adults from Northern Colorado," IJERPH, MDPI, vol. 18(21), pages 1-9, October.
    3. Tiago Fazolo & Karina Lima & Julia C. Fontoura & Priscila Oliveira Souza & Gabriel Hilario & Renata Zorzetto & Luiz Rodrigues Júnior & Veridiane Maria Pscheidt & Jayme Castilhos Ferreira Neto & Alisso, 2021. "Pediatric COVID-19 patients in South Brazil show abundant viral mRNA and strong specific anti-viral responses," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Fábio Santos Lira & Telmo Pereira & Luciele Guerra Minuzzi & Caique Figueiredo & Tiago Olean-Oliveira & Ana Paula Coelho Figueira Freire & Manuel João Coelho-e-Silva & Armando Caseiro & Ronaldo Vagner, 2021. "Modulatory Effects of Physical Activity Levels on Immune Responses and General Clinical Functions in Adult Patients with Mild to Moderate SARS-CoV-2 Infections—A Protocol for an Observational Prospect," IJERPH, MDPI, vol. 18(24), pages 1-13, December.
    5. Lucie Bernard-Raichon & Mericien Venzon & Jon Klein & Jordan E. Axelrad & Chenzhen Zhang & Alexis P. Sullivan & Grant A. Hussey & Arnau Casanovas-Massana & Maria G. Noval & Ana M. Valero-Jimenez & Jua, 2022. "Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    6. Sunil K. Ahuja & Muthu Saravanan Manoharan & Grace C. Lee & Lyle R. McKinnon & Justin A. Meunier & Maristella Steri & Nathan Harper & Edoardo Fiorillo & Alisha M. Smith & Marcos I. Restrepo & Anne P. , 2023. "Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection," Nature Communications, Nature, vol. 14(1), pages 1-31, December.
    7. Hideki Ogura & Jin Gohda & Xiuyuan Lu & Mizuki Yamamoto & Yoshio Takesue & Aoi Son & Sadayuki Doi & Kazuyuki Matsushita & Fumitaka Isobe & Yoshihiro Fukuda & Tai-Ping Huang & Takamasa Ueno & Naomi Mam, 2022. "Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Changli Wei & Prasun K. Datta & Florian Siegerist & Jing Li & Sudhini Yashwanth & Kwi Hye Koh & Nicholas W. Kriho & Anis Ismail & Shengyuan Luo & Tracy Fischer & Kyle T. Amber & David Cimbaluk & Alan , 2023. "SuPAR mediates viral response proteinuria by rapidly changing podocyte function," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    9. Ilya Tsukalov & Ildefonso Sánchez-Cerrillo & Olga Rajas & Elena Avalos & Gorane Iturricastillo & Laura Esparcia & María José Buzón & Meritxell Genescà & Camila Scagnetti & Olga Popova & Noa Martin-Cóf, 2024. "NFκB and NLRP3/NLRC4 inflammasomes regulate differentiation, activation and functional properties of monocytes in response to distinct SARS-CoV-2 proteins," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    10. Manon Venet & Margarida Sa Ribeiro & Elodie Décembre & Alicia Bellomo & Garima Joshi & Célia Nuovo & Marine Villard & David Cluet & Magali Perret & Rémi Pescamona & Helena Paidassi & Thierry Walzer & , 2023. "Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    11. Quy Xiao Xuan Lin & Deepa Rajagopalan & Akshamal M. Gamage & Le Min Tan & Prasanna Nori Venkatesh & Wharton O. Y. Chan & Dilip Kumar & Ragini Agrawal & Yao Chen & Siew-Wai Fong & Amit Singh & Louisa J, 2024. "Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    12. Matthew C. Woodruff & Kevin S. Bonham & Fabliha A. Anam & Tiffany A. Walker & Caterina E. Faliti & Yusho Ishii & Candice Y. Kaminski & Martin C. Ruunstrom & Kelly Rose Cooper & Alexander D. Truong & A, 2023. "Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    13. Al Ozonoff & Naresh Doni Jayavelu & Shanshan Liu & Esther Melamed & Carly E. Milliren & Jingjing Qi & Linda N. Geng & Grace A. McComsey & Charles B. Cairns & Lindsey R. Baden & Joanna Schaenman & Albe, 2024. "Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    14. Wei Feng & Joanne C. Beer & Qinyu Hao & Ishara S. Ariyapala & Aparna Sahajan & Andrei Komarov & Katie Cha & Mason Moua & Xiaolei Qiu & Xiaomei Xu & Shweta Iyengar & Thu Yoshimura & Rajini Nagaraj & Li, 2023. "NULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    15. Clovis S. Palmer & Chrysostomos Perdios & Mohamed Abdel-Mohsen & Joseph Mudd & Prasun K. Datta & Nicholas J. Maness & Gabrielle Lehmicke & Nadia Golden & Linh Hellmers & Carol Coyne & Kristyn Moore Gr, 2024. "Non-human primate model of long-COVID identifies immune associates of hyperglycemia," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    16. Yvonne M. Mueller & Thijs J. Schrama & Rik Ruijten & Marco W. J. Schreurs & Dwin G. B. Grashof & Harmen J. G. van de Werken & Giovanna Jona Lasinio & Daniel Álvarez-Sierra & Caoimhe H. Kiernan & Melis, 2022. "Stratification of hospitalized COVID-19 patients into clinical severity progression groups by immuno-phenotyping and machine learning," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    17. Olga Scudiero & Barbara Lombardo & Mariarita Brancaccio & Cristina Mennitti & Arturo Cesaro & Fabio Fimiani & Luca Gentile & Elisabetta Moscarella & Federica Amodio & Annaluisa Ranieri & Felice Gragna, 2021. "Exercise, Immune System, Nutrition, Respiratory and Cardiovascular Diseases during COVID-19: A Complex Combination," IJERPH, MDPI, vol. 18(3), pages 1-20, January.
    18. Minami Nagai & Miyu Moriyama & Chiharu Ishii & Hirotake Mori & Hikaru Watanabe & Taku Nakahara & Takuji Yamada & Dai Ishikawa & Takamasa Ishikawa & Akiyoshi Hirayama & Ikuo Kimura & Akihito Nagahara &, 2023. "High body temperature increases gut microbiota-dependent host resistance to influenza A virus and SARS-CoV-2 infection," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34895-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.