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

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.

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.