SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike

Guthmiller, Jenna J.; Stovicek, Olivia; Wang, Jiaolong; Changrob, Siriruk; Li, Lei; Halfmann, Peter; Zheng, Nai-Ying; Utset, Henry; Stamper, Christopher T.; Dugan, Haley L.; Miller, William D.; Huang, Min; Dai, Ya-Nan; Nelson, Christopher A.; Hall, Paige D.; Jansen, Maud; Shanmugarajah, Kumaran; Donington, Jessica S.; Krammer, Florian; Fremont, Daved H.; Joachimiak, Andrzej; Kawaoka, Yoshihiro; Tesic, Vera; Madariaga, Maria Lucia; Wilson, Patrick C.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity of the antibody response mounted against this novel virus is not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and nonstructural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.