Quick COVID-19 Healers Sustain Anti-SARS-CoV-2 Antibody Production

• Published in: Cell Vol. 183; no. 6; pp. 1496 - 1507.e16
• Main Authors: Chen, Yuezhou, Zuiani, Adam, Fischinger, Stephanie, Mullur, Jyotsna, Atyeo, Caroline, Travers, Meghan, Lelis, Felipe J.N., Pullen, Krista M., Martin, Hannah, Tong, Pei, Gautam, Avneesh, Habibi, Shaghayegh, Bensko, Jillian, Gakpo, Deborah, Feldman, Jared, Hauser, Blake M., Caradonna, Timothy M., Cai, Yongfei, Burke, John S., Lin, Junrui, Lederer, James A., Lam, Evan Christopher, Lavine, Christy L., Seaman, Michael S., Chen, Bing, Schmidt, Aaron G., Balazs, Alejandro Benjamin, Lauffenburger, Douglas A., Alter, Galit, Wesemann, Duane R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.12.2020
• Subjects: antibodies; Antibodies, Viral - immunology; Antibody Formation; B-lymphocytes; CD4-Positive T-Lymphocytes - immunology; COVID-19; COVID-19 - genetics; COVID-19 - immunology; COVID-19 infection; durability; germinal center; Humans; Immunoglobulin G - immunology; longevity; Lymphocyte Activation; Mutation; phenotype; SARS-CoV-2; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; serology; Severe acute respiratory syndrome coronavirus 2; severity; SHM; somatic hypermutation; symptom duration; COVID-19; severity; SARS-CoV-2; somatic hypermutation; symptom duration; serology; durability; SHM; germinal center
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2020.10.051

Antibodies are key immune effectors that confer protection against pathogenic threats. The nature and longevity of the antibody response to SARS-CoV-2 infection are 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 time frame 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 symptom clearance speed to differential antibody durability dynamics. [Display omitted] •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.