1. Quick COVID-19 Healers Sustain Anti-SARS-CoV-2 Antibody Production
- Author
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Yongfei Cai, Michael S. Seaman, Krista M. Pullen, Deborah Gakpo, Duane R. Wesemann, Bing Chen, James A. Lederer, Douglas A. Lauffenburger, Jared Feldman, Aaron G. Schmidt, Pei Tong, Adam Zuiani, John S. Burke, Alejandro B. Balazs, Junrui Lin, Evan C. Lam, Hannah Martin, Avneesh Gautam, Jyotsna Mullur, Blake M. Hauser, Jillian C. Bensko, Timothy M. Caradonna, Stephanie Fischinger, Caroline Atyeo, Christy L. Lavine, Felipe J.N. Lelis, Yuezhou Chen, Meghan Travers, Shaghayegh Habibi, and Galit Alter
- Subjects
CD4-Positive T-Lymphocytes ,Somatic hypermutation ,Antibodies, Viral ,Lymphocyte Activation ,medicine.disease_cause ,Article ,General Biochemistry, Genetics and Molecular Biology ,Immunoglobulin G ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Humans ,Memory B cell ,030304 developmental biology ,0303 health sciences ,Mutation ,biology ,SARS-CoV-2 ,COVID-19 ,Germinal center ,Antibody Formation ,Immunology ,biology.protein ,Antibody ,030217 neurology & neurosurgery - Abstract
Antibodies are key immune effectors that confer protection against pathogenic threats. The nature and longevity of the antibody response to SARS-CoV-2 infection is not well defined. We charted longitudinal antibody responses to SARS-CoV-2 in 92 subjects after symptomatic COVID-19. Antibody responses to SARS-CoV-2 are unimodally distributed over a broad range, with symptom severity correlating directly with virus-specific antibody magnitude. Seventy-six subjects followed longitudinally to ∼100 days demonstrated marked heterogeneity in antibody duration dynamics. Virus-specific IgG decayed substantially in most individuals, whereas a distinct subset had stable or increasing antibody levels in the same timeframe despite similar initial antibody magnitudes. These individuals with increasing responses recovered rapidly from symptomatic COVID-19 disease, harbored increased somatic mutations in virus-specific memory B cell antibody genes, and had persistent higher frequencies of previously activated CD4+ T cells. These findings illuminate an efficient immune phenotype that connects rapid symptom clearance to differential antibody durability dynamics., Highlights SARS-CoV-2 antibody responses range from negligible to robust in mild COVID-19 Some individuals maintain stable or increased SARS-CoV-2 IgG, while most decline Those who sustain virus-specific IgG production tend to have shorter disease courses Virus-specific B cells from “sustainers” have more SHM early after disease resolution, Longitudinal analyses of antibody responses to SARS-CoV-2 demonstrate that individuals with sustained virus-specific IgG production have shorter disease trajectories, with a subset demonstrating increased somatic hypermutation and higher levels of activated CD4+ cells.
- Published
- 2020
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