1. Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low Prevalence Communities and Reveal Durable Humoral Immunity
- Author
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Makiko Watanabe, Christine M. Bradshaw, Tyler J. Ripperger, Cameron Hypes, Matthew E. Kaplan, Michael Insel, Craig Weinkauf, David T. Harris, Bonnie LaFleur, Rachel O.L. Wong, Elaine Cristan, Afshin Sam, Franz Rischard, Madhav Chopra, Michael D. Dake, Janko Nikolich-Žugich, Taylor Edwards, Janet Campion, Hannah A. Pizzato, Kenneth S. Knox, Sairam Parthasarathy, Deepta Bhattacharya, Serena Jain Scott, Billie Bixby, Christian Bime, Tammer El Aini, Yvonne Castaneda, Sachin Chaudhary, Bhupinder Natt, Mallory R. Thompson, Andrew P. Capaldi, Ryan Sprissler, Jarrod Mosier, Heidi Erickson, Jennifer L. Uhrlaub, Catherine M. Spier, and James Knepler
- Subjects
0301 basic medicine ,Immunology ,Seroepidemiologic Studies ,Biology ,Virology ,Neutralization ,Serology ,03 medical and health sciences ,Titer ,030104 developmental biology ,0302 clinical medicine ,Infectious Diseases ,Antigen ,Immunity ,030220 oncology & carcinogenesis ,Report ,Humoral immunity ,biology.protein ,Immunology and Allergy ,Antibody - Abstract
We conducted a serological study to define correlates of immunity against SARS-CoV-2. Relative to mild COVID-19 cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies against nucleocapsid (N) and the receptor binding domain (RBD) of spike protein. Age and sex played lesser roles. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. Spike RBD and S2 and neutralizing antibodies remained detectable through 5-7 months post-onset, whereas α-N titers diminished. Testing of 5882 members of the local community revealed only 1 sample with seroreactivity to both RBD and S2 that lacked neutralizing antibodies. This fidelity could not be achieved with either RBD or S2 alone. Thus, inclusion of multiple independent assays improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the antigen. We conclude that neutralizing antibodies are stably produced for at least 5-7 months after SARS-CoV-2 infection., Graphical Abstract, Highlights • Using independent SARS-CoV-2 antigens improves specificity of serological assays • Neutralizing and spike-specific antibody production persists for at least 5-7 months • Nucleocapsid antibodies frequently become undetectable by 5-7 months • Antibody production is higher in severe disease relative to mild cases, Serological assays for SARS-CoV-2 exposures are challenging due to poor positive predictive values. Ripperger et al. show that combinatorial use of spike receptor binding domain and S2 eliminates almost all false positives. This serological assay is used to show durable antibody production for at least 5-7 months after infection.
- Published
- 2020