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Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19

Author

Listed:
  • Meng Yu

    (Karolinska University Hospital)

  • Afandi Charles

    (Karolinska University Hospital)

  • Alberto Cagigi

    (Karolinska University Hospital)

  • Wanda Christ

    (Karolinska Institutet)

  • Björn Österberg

    (Karolinska University Hospital)

  • Sara Falck-Jones

    (Karolinska University Hospital)

  • Lida Azizmohammadi

    (Karolinska University Hospital)

  • Eric Åhlberg

    (Karolinska University Hospital)

  • Ryan Falck-Jones

    (Karolinska Institutet
    Karolinska University Hospital)

  • Julia Svensson

    (Karolinska University Hospital)

  • Mu Nie

    (Karolinska University Hospital)

  • Anna Warnqvist

    (Karolinska Institutet)

  • Fredrika Hellgren

    (Karolinska University Hospital)

  • Klara Lenart

    (Karolinska University Hospital)

  • Rodrigo Arcoverde Cerveira

    (Karolinska University Hospital)

  • Sebastian Ols

    (Karolinska University Hospital)

  • Gustaf Lindgren

    (Karolinska University Hospital)

  • Ang Lin

    (Karolinska University Hospital)

  • Holden Maecker

    (Stanford University School of Medicine)

  • Max Bell

    (Karolinska Institutet
    Karolinska University Hospital)

  • Niclas Johansson

    (Karolinska Institutet
    Karolinska University Hospital Solna)

  • Jan Albert

    (Karolinska Institutet
    Karolinska University Hospital Solna)

  • Christopher Sundling

    (Karolinska Institutet
    Karolinska University Hospital Solna)

  • Paulo Czarnewski

    (Stockholm University)

  • Jonas Klingström

    (Karolinska Institutet
    Linköping University)

  • Anna Färnert

    (Karolinska Institutet
    Karolinska University Hospital Solna)

  • Karin Loré

    (Karolinska University Hospital)

  • Anna Smed-Sörensen

    (Karolinska University Hospital)

Abstract

Effective humoral immune responses require well-orchestrated B and T follicular helper (Tfh) cell interactions. Whether these interactions are impaired and associated with COVID-19 disease severity is unclear. Here, longitudinal blood samples across COVID-19 disease severity are analysed. We find that during acute infection SARS-CoV-2-specific circulating Tfh (cTfh) cells expand with disease severity. SARS-CoV-2-specific cTfh cell frequencies correlate with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, from severe patients better induce plasmablast differentiation and antibody production compared to cTfh cells from mild patients. However, virus-specific cTfh cell development is delayed in patients that display or later develop severe disease compared to those with mild disease, which correlates with delayed induction of high-avidity neutralizing antibodies. Our study suggests that impaired generation of functional virus-specific cTfh cells delays high-quality antibody production at an early stage, potentially enabling progression to severe disease.

Suggested Citation

  • Meng Yu & Afandi Charles & Alberto Cagigi & Wanda Christ & Björn Österberg & Sara Falck-Jones & Lida Azizmohammadi & Eric Åhlberg & Ryan Falck-Jones & Julia Svensson & Mu Nie & Anna Warnqvist & Fredri, 2023. "Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37835-9
    DOI: 10.1038/s41467-023-37835-9
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    References listed on IDEAS

    as
    1. Juanjie Tang & Supriya Ravichandran & Youri Lee & Gabrielle Grubbs & Elizabeth M. Coyle & Laura Klenow & Hollie Genser & Hana Golding & Surender Khurana, 2021. "Antibody affinity maturation and plasma IgA associate with clinical outcome in hospitalized COVID-19 patients," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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