Longitudinal antibody repertoire in “mild” versus “severe” COVID-19 patients reveals immune markers associated with disease severity and resolution
Supriya Ravichandran, Youri Lee, Gabrielle Grubbs, Elizabeth M. Coyle, Laura Klenow, Osamu Akasaka, Michiko Koga, Eisuke Adachi, Makoto Saito, Ichiro Nakachi, Takayuki Ogura, Rie Baba, Mutsumi Ito, Maki Kiso, Atsuhiro Yasuhara, Shinya Yamada, Yuko Sakai‐Tagawa, Kiyoko Iwatsuki‐Horimoto, Masaki Imai, Seiya Yamayoshi, Hiroshi Yotsuyanagi, Yoshihiro Kawaoka, Surender Khurana
Abstract
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.