IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v603y2022i7902d10.1038_s41586-022-04447-0.html
   My bibliography  Save this article

Human genetic and immunological determinants of critical COVID-19 pneumonia

Author

Listed:
  • Qian Zhang

    (The Rockefeller University
    Necker Hospital for Sick Children
    Imagine Institute)

  • Paul Bastard

    (The Rockefeller University
    Necker Hospital for Sick Children
    Imagine Institute
    Necker Hospital for Sick Children)

  • Aurélie Cobat

    (The Rockefeller University
    Necker Hospital for Sick Children
    Imagine Institute)

  • Jean-Laurent Casanova

    (The Rockefeller University
    Necker Hospital for Sick Children
    Imagine Institute
    Necker Hospital for Sick Children)

Abstract

SARS-CoV-2 infection is benign in most individuals but, in around 10% of cases, it triggers hypoxaemic COVID-19 pneumonia, which leads to critical illness in around 3% of cases. The ensuing risk of death (approximately 1% across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. Here we review the molecular and cellular determinants of critical COVID-19 pneumonia. Inborn errors of type I interferons (IFNs), including autosomal TLR3 and X-chromosome-linked TLR7 deficiencies, are found in around 1–5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing auto-antibodies neutralizing IFNα, IFNβ and/or IFNω, which are more common in men than in women, are found in approximately 15–20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defence against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:nature:v:603:y:2022:i:7902:d:10.1038_s41586-022-04447-0
    DOI: 10.1038/s41586-022-04447-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-022-04447-0
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-022-04447-0?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    References listed on IDEAS

    as
    1. Sen Pei & Teresa K. Yamana & Sasikiran Kandula & Marta Galanti & Jeffrey Shaman, 2021. "Burden and characteristics of COVID-19 in the United States during 2020," Nature, Nature, vol. 598(7880), pages 338-341, October.
    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. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.

    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. Haobo Ni & Xiaoyan Cai & Jiarong Ren & Tingting Dai & Jiayi Zhou & Jiumin Lin & Li Wang & Lingxi Wang & Sen Pei & Yunchong Yao & Ting Xu & Lina Xiao & Qiyong Liu & Xiaobo Liu & Pi Guo, 2024. "Epidemiological characteristics and transmission dynamics of dengue fever in China," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Sen Pei & Sasikiran Kandula & Jaime Cascante Vega & Wan Yang & Steffen Foerster & Corinne Thompson & Jennifer Baumgartner & Shama Desai Ahuja & Kathleen Blaney & Jay K. Varma & Theodore Long & Jeffrey, 2022. "Contact tracing reveals community transmission of COVID-19 in New York City," Nature Communications, Nature, vol. 13(1), pages 1-8, 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:nature:v:603:y:2022:i:7902:d:10.1038_s41586-022-04447-0. 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.