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Antibody affinity maturation and plasma IgA associate with clinical outcome in hospitalized COVID-19 patients

Author

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  • Juanjie Tang

    (Center for Biologics Evaluation and Research (CBER), FDA)

  • Supriya Ravichandran

    (Center for Biologics Evaluation and Research (CBER), FDA)

  • Youri Lee

    (Center for Biologics Evaluation and Research (CBER), FDA)

  • Gabrielle Grubbs

    (Center for Biologics Evaluation and Research (CBER), FDA)

  • Elizabeth M. Coyle

    (Center for Biologics Evaluation and Research (CBER), FDA)

  • Laura Klenow

    (Center for Biologics Evaluation and Research (CBER), FDA)

  • Hollie Genser

    (Quest Diagnostics at Adventist Healthcare)

  • Hana Golding

    (Center for Biologics Evaluation and Research (CBER), FDA)

  • Surender Khurana

    (Center for Biologics Evaluation and Research (CBER), FDA)

Abstract

Hospitalized COVID-19 patients often present with a large spectrum of clinical symptoms. There is a critical need to better understand the immune responses to SARS-CoV-2 that lead to either resolution or exacerbation of the clinical disease. Here, we examine longitudinal plasma samples from hospitalized COVID-19 patients with differential clinical outcome. We perform immune-repertoire analysis including cytokine, hACE2-receptor inhibition, neutralization titers, antibody epitope repertoire, antibody kinetics, antibody isotype and antibody affinity maturation against the SARS-CoV-2 prefusion spike protein. Fatal cases demonstrate high plasma levels of IL-6, IL-8, TNFα, and MCP-1, and sustained high percentage of IgA-binding antibodies to prefusion spike compared with non-ICU survivors. Disease resolution in non-ICU and ICU patients associates with antibody binding to the receptor binding motif and fusion peptide, and antibody affinity maturation to SARS-CoV-2 prefusion spike protein. Here, we provide insight into the immune parameters associated with clinical disease severity and disease-resolution outcome in hospitalized patients that could inform development of vaccine/therapeutics against COVID-19.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21463-2
    DOI: 10.1038/s41467-021-21463-2
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    Cited by:

    1. Juanjie Tang & Tanya Novak & Julian Hecker & Gabrielle Grubbs & Fatema Tuz Zahra & Lorenza Bellusci & Sara Pourhashemi & Janet Chou & Kristin Moffitt & Natasha B. Halasa & Stephanie P. Schwartz & Trac, 2022. "Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. 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.
    3. Lorenza Bellusci & Gabrielle Grubbs & Fatema Tuz Zahra & David Forgacs & Hana Golding & Ted M. Ross & Surender Khurana, 2022. "Antibody affinity and cross-variant neutralization of SARS-CoV-2 Omicron BA.1, BA.2 and BA.3 following third mRNA vaccination," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    4. 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.
    5. Lorenza Bellusci & Gabrielle Grubbs & Shaimaa Sait & Lael M. Yonker & Adrienne G. Randolph & Tanya Novak & Takuma Kobayashi & Surender Khurana, 2023. "Neutralization of SARS-CoV-2 Omicron BQ.1, BQ.1.1 and XBB.1 variants following SARS-CoV-2 infection or vaccination in children," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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