Dynamics and significance of the antibody response to SARS-CoV-2 infection
Anita S Iyer, Forrest K Jones, Ariana Nodoushani, Meagan Kelly, Margaret Becker, Damien Slater, Rachel Mills, Erica Teng, Mohammad Kamruzzaman, Wilfredo F Garcia-Beltran, Michael Astudillo, Diane Yang, Tyler E Miller, Elizabeth Oliver, Stephanie Fischinger, Caroline Atyeo, A John Iafrate, Stephen B Calderwood, Stephen A Lauer, Jingyou Yu, Zhenfeng Li, Jared Feldman, Blake M Hauser, Timothy M Caradonna, John A Branda, Sarah E Turbett, Regina C LaRocque, Guillaume Mellon, Dan H Barouch, Aaron G Schmidt, Andrew S Azman, Galit Alter, Edward T Ryan, Jason B Harris, Richelle C Charles, Anita S Iyer, Forrest K Jones, Ariana Nodoushani, Meagan Kelly, Margaret Becker, Damien Slater, Rachel Mills, Erica Teng, Mohammad Kamruzzaman, Wilfredo F Garcia-Beltran, Michael Astudillo, Diane Yang, Tyler E Miller, Elizabeth Oliver, Stephanie Fischinger, Caroline Atyeo, A John Iafrate, Stephen B Calderwood, Stephen A Lauer, Jingyou Yu, Zhenfeng Li, Jared Feldman, Blake M Hauser, Timothy M Caradonna, John A Branda, Sarah E Turbett, Regina C LaRocque, Guillaume Mellon, Dan H Barouch, Aaron G Schmidt, Andrew S Azman, Galit Alter, Edward T Ryan, Jason B Harris, Richelle C Charles
Abstract
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.
Figures
References
- Lipsitch M, Swerdlow DL, Finelli L. Defining the Epidemiology of Covid-19 - Studies Needed. N Engl J Med 2020;382:1194–6.
- WHO Coronavirus Disease (COVID-19) Dashboard. A . Accessed 14th July,2020.
- Zohar T, Alter G. Dissecting antibody-mediated protection against SARS-CoV-2. Nat Rev Immunol 2020;20:392–4.
- Dohla M, Boesecke C, Schulte B, et al. Rapid point-of-care testing for SARS-CoV-2 in a community screening setting shows low sensitivity. Public Health 2020;182:170–2.
- Wang C, Li W, Drabek D, et al. Publisher Correction: A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun 2020;11:2511.
- Chandrashekar A, Liu J, Martinot AJ, et al. SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science 2020. Published online 2020 May 20. doi: 10.1126/science.abc4776
- Yu J, Tostanoski LH, Peter L, et al. DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science 2020. doi: 10.1126/science.abc6284
- Bryant JE, Azman AS, Ferrari MJ, et al. Serology for SARS-CoV-2: Apprehensions, opportunities, and the path forward. Sci Immunol 2020;5. doi: 10.1126/sciimmunol.abc6347
- Anderson-Bergman C. icenReg: Regression Models for Interval Censored Data in R. 2017.
- Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure. Ann Intern Med 2020. Published online 2020 May 13. doi: 10.7326/M20-1495
- Guo L, Ren L, Yang S, et al. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clin Infect Dis 2020. Published online 2020 Mar 21. doi: 10.1093/cid/ciaa310
- Yong SEF, Anderson DE, Wei WE, et al. Connecting clusters of COVID-19: an epidemiological and serological investigation. Lancet Infect Dis 2020. doi:10.1016/S1473-3099(20)30273-5
- Long QX, Tang XJ, Shi QL, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 2020. doi: 10.1038/s41591-020-0965-6
- Antibody Test, Seen as Key to Reopening Country, Does Not Yet Deliver. The New York Times; Published April 19, 2020.
- Antibody tests for Covid-19 wrong up to half the time, CDC says. Published CNN May 26, 2020.
- Ko JH, Muller MA, Seok H, et al. Serologic responses of 42 MERS-coronavirus-infected patients according to the disease severity. Diagn Microbiol Infect Dis 2017;89:106–11.
- Huang AT, Garcia-Carreras B, Hitchings MDT, et al. A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease. medRxiv 2020. Preprint. 2020 Apr 17. doi: 10.1101/2020.04.14.20065771
- Elena Criscuolo RAD, Marta Strollo, Serena Rolla et al. Poor correlation between antibody titers and neutralizing activity in sera from SARS-CoV-2 infected subjects. medRxiv. 2020. Preprint. 2020 July 11 2020. doi: 10.1101/2020.07.10.20150375
- Centers for Disease Control and Prevention. Interim Guidelines for COVID-19 Antibody Testing. 2020. at . Accessed 13th, July 2020.
Source: PubMed