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Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity.
Immunity. 2020 11 17; 53(5):925-933.e4.I

Abstract

We conducted a serological study to define correlates of immunity against SARS-CoV-2. Compared to those with mild coronavirus disease 2019 (COVID-19) cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies against the nucleocapsid (N) and the receptor binding domain (RBD) of the spike protein. Age and sex played lesser roles. All cases, including asymptomatic individuals, seroconverted by 2 weeks after PCR confirmation. Spike RBD and S2 and neutralizing antibodies remained detectable through 5-7 months after onset, whereas α-N titers diminished. Testing 5,882 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.

Authors+Show Affiliations

Department of Immunobiology, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Department of Immunobiology, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; University of Arizona Center on Aging, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Department of Immunobiology, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; University of Arizona Center on Aging, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Department of Immunobiology, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; Division of Biological and Biomedical Sciences, Washington University, St. Louis, MO, USA.Department of Immunobiology, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; University of Arizona Center on Aging, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Department of Immunobiology, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; Division of Biological and Biomedical Sciences, Washington University, St. Louis, MO, USA.Department of Surgery, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; Department of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Department of Immunobiology, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; University of Arizona Center on Aging, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Department of Surgery, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; Department of Medicine, University of Arizona, Phoenix, Phoenix, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Department of Molecular and Cellular Biology, University of Arizona, Tucson, Tucson, AZ, USA; Functional Genomics Core, University of Arizona, Tucson, AZ, USA.Department of Pathology, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Office of the Senior Vice-President for Health Sciences, University of Arizona, Tucson, AZ, USA.University of Arizona Genomics Core and the Arizona Research Labs, University of Arizona Genetics Core, University of Arizona, Tucson, AZ, USA.Functional Genomics Core, University of Arizona, Tucson, AZ, USA.Division of Geriatrics, General Medicine and Palliative Care, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; Department of Emergency Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; Department of Emergency Medicine, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA.Department of Immunobiology, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; University of Arizona Health Sciences Biobank, University of Arizona, Tucson, AZ, USA.BIO5 Institute, University of Arizona, Tucson, AZ, USA.University of Arizona Genomics Core and the Arizona Research Labs, University of Arizona Genetics Core, University of Arizona, Tucson, AZ, USA; BIO5 Institute, University of Arizona, Tucson, AZ, USA.Department of Immunobiology, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; University of Arizona Center on Aging, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; BIO5 Institute, University of Arizona, Tucson, AZ, USA. Electronic address: nikolich@arizona.edu.Department of Immunobiology, University of Arizona College of Medicine, Tucson, Tucson, AZ, USA; BIO5 Institute, University of Arizona, Tucson, AZ, USA. Electronic address: deeptab@arizona.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

33129373

Citation

Ripperger, Tyler J., et al. "Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity." Immunity, vol. 53, no. 5, 2020, pp. 925-933.e4.
Ripperger TJ, Uhrlaub JL, Watanabe M, et al. Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity. Immunity. 2020;53(5):925-933.e4.
Ripperger, T. J., Uhrlaub, J. L., Watanabe, M., Wong, R., Castaneda, Y., Pizzato, H. A., Thompson, M. R., Bradshaw, C., Weinkauf, C. C., Bime, C., Erickson, H. L., Knox, K., Bixby, B., Parthasarathy, S., Chaudhary, S., Natt, B., Cristan, E., El Aini, T., Rischard, F., ... Bhattacharya, D. (2020). Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity. Immunity, 53(5), 925-e4. https://doi.org/10.1016/j.immuni.2020.10.004
Ripperger TJ, et al. Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity. Immunity. 2020 11 17;53(5):925-933.e4. PubMed PMID: 33129373.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity. AU - Ripperger,Tyler J, AU - Uhrlaub,Jennifer L, AU - Watanabe,Makiko, AU - Wong,Rachel, AU - Castaneda,Yvonne, AU - Pizzato,Hannah A, AU - Thompson,Mallory R, AU - Bradshaw,Christine, AU - Weinkauf,Craig C, AU - Bime,Christian, AU - Erickson,Heidi L, AU - Knox,Kenneth, AU - Bixby,Billie, AU - Parthasarathy,Sairam, AU - Chaudhary,Sachin, AU - Natt,Bhupinder, AU - Cristan,Elaine, AU - El Aini,Tammer, AU - Rischard,Franz, AU - Campion,Janet, AU - Chopra,Madhav, AU - Insel,Michael, AU - Sam,Afshin, AU - Knepler,James L, AU - Capaldi,Andrew P, AU - Spier,Catherine M, AU - Dake,Michael D, AU - Edwards,Taylor, AU - Kaplan,Matthew E, AU - Scott,Serena Jain, AU - Hypes,Cameron, AU - Mosier,Jarrod, AU - Harris,David T, AU - LaFleur,Bonnie J, AU - Sprissler,Ryan, AU - Nikolich-Žugich,Janko, AU - Bhattacharya,Deepta, Y1 - 2020/10/14/ PY - 2020/07/31/received PY - 2020/10/01/revised PY - 2020/10/05/accepted PY - 2020/11/2/pubmed PY - 2020/12/1/medline PY - 2020/11/1/entrez KW - COVID-19 KW - S2 domain KW - SARS-CoV-2 KW - antibodies KW - neutralization KW - nucleocapsid protein KW - orthogonal serological tests KW - receptor binding domain KW - serological test KW - serology KW - spike protein SP - 925 EP - 933.e4 JF - Immunity JO - Immunity VL - 53 IS - 5 N2 - We conducted a serological study to define correlates of immunity against SARS-CoV-2. Compared to those with mild coronavirus disease 2019 (COVID-19) cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies against the nucleocapsid (N) and the receptor binding domain (RBD) of the spike protein. Age and sex played lesser roles. All cases, including asymptomatic individuals, seroconverted by 2 weeks after PCR confirmation. Spike RBD and S2 and neutralizing antibodies remained detectable through 5-7 months after onset, whereas α-N titers diminished. Testing 5,882 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. SN - 1097-4180 UR - https://www.unboundmedicine.com/medline/citation/33129373/Orthogonal_SARS_CoV_2_Serological_Assays_Enable_Surveillance_of_Low_Prevalence_Communities_and_Reveal_Durable_Humoral_Immunity_ DB - PRIME DP - Unbound Medicine ER -