Longitudinal antibody repertoire in “mild” versus “severe” COVID-19 patients reveals immune markers associated with disease severity and resolution

Ravichandran, Supriya; Lee, Youri; Grubbs, Gabrielle; Coyle, Elizabeth M.; Klenow, Laura; Akasaka, Osamu; Koga, Michiko; Adachi, Eisuke; Saito, Makoto; Nakachi, Ichiro; Ogura, Takayuki; Baba, Rie; Ito, Mutsumi; Kiso, Maki; Yasuhara, Atsuhiro; Yamada, Shinya; Sakai-Tagawa, Yuko; Iwatsuki-Horimoto, Kiyoko; Imai, Masaki; Yamayoshi, Seiya; Yotsuyanagi, Hiroshi; Kawaoka, Yoshihiro; Khurana, Surender

Limited knowledge exists on immune markers associated with disease severity or recovery in patients with coronavirus disease 2019 (COVID-19). Here, we elucidated longitudinal evolution of SARS-CoV-2 antibody repertoire in patients with acute COVID-19. Differential kinetics was observed for immunoglobulin M (IgM)/IgG/IgA epitope diversity, antibody binding, and affinity maturation in “severe” versus “mild” COVID-19 patients. IgG profile demonstrated immunodominant antigenic sequences encompassing fusion peptide and receptor binding domain (RBD) in patients with mild COVID-19 who recovered early compared with “fatal” COVID-19 patients. In patients with severe COVID-19, high-titer IgA were observed, primarily against RBD, especially in patients who succumbed to SARS-CoV-2 infection. The patients with mild COVID-19 showed marked increase in antibody affinity maturation to prefusion SARS-CoV-2 spike that associated with faster recovery from COVID-19. This study revealed antibody markers associated with disease severity and resolution of clinical disease that could inform development and evaluation of effective immune-based countermeasures against COVID-19.