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

Juanjie Tang, Supriya Ravichandran, Youri Lee, Gabrielle Grubbs, Elizabeth M. Coyle, Laura Klenow, Hollie Genser, Hana Golding and Surender Khurana ()
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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

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21463-2

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