Dynamics and significance of the antibody response to SARS-CoV-2 infection

Iyer, Anita S.; Jones, Forrest K.; Nodoushani, Ariana; Kelly, Meagan; Becker, Margaret; Slater, Damien; Mills, Rachel; Teng, Erica; Kamruzzaman, Mohammad; Garcia-Beltran, Wilfredo F.; Astudillo, Michael; Yang, Diane; Miller, Tyler E.; Oliver, Elizabeth; Fischinger, Stephanie; Atyeo, Caroline; Iafrate, A. John; Calderwood, Stephen B.; Lauer, Stephen A.; Yu, Jingyou; Li, Zhenfeng; Feldman, Jared; Hauser, Blake M.; Caradonna, Timothy M.; Branda, John A.; Turbett, Sarah E.; LaRocque, Regina C.; Mellon, Guillaume; Barouch, Dan H.; Schmidt, Aaron G.; Azman, Andrew S.; Alter, Galit; Ryan, Edward T; Harris, Jason B.; Charles, Richelle C.

BACKGROUND: Characterizing the humoral immune response to SARS-CoV-2 and developing accurate serologic assays are needed for diagnostic purposes and estimating population-level seroprevalence. METHODS: We measured the kinetics of early antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in a cohort of 259 symptomatic North American patients infected with SARS-CoV-2 (up to 75 days after symptom onset) compared to antibody levels in 1548 individuals whose blood samples were obtained prior to the pandemic. RESULTS: Between 14–28 days from onset of symptoms, IgG, IgA, or IgM antibody responses to RBD were all accurate in identifying recently infected individuals, with 100% specificity and a sensitivity of 97%, 91%, and 81% respectively. Although the estimated median time to becoming seropositive was similar across isotypes, IgA and IgM antibodies against RBD were short-lived with most individuals estimated to become seronegative again by 51 and 47 days after symptom onset, respectively. IgG antibodies against RBD lasted longer and persisted through 75 days post-symptoms. IgG antibodies to SARS-CoV-2 RBD were highly correlated with neutralizing antibodies targeting the S protein. No cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies was observed with several known circulating coronaviruses, HKU1, OC 229 E, OC43, and NL63. CONCLUSIONS: Among symptomatic SARS-CoV-2 cases, RBD-targeted antibodies can be indicative of previous and recent infection. IgG antibodies are correlated with neutralizing antibodies and are possibly a correlate of protective immunity.