@article{22878db0087b4927adb68b3fcdfd1076,
title = "Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity",
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. Serological assays for SARS-CoV-2 exposures are challenging due to poor positive predictive values. Ripperger et al. show that the 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.",
keywords = "COVID-19, S2 domain, SARS-CoV-2, antibodies, neutralization, nucleocapsid protein, orthogonal serological tests, receptor binding domain, serological test, serology, spike protein",
author = "Ripperger, {Tyler J.} and Uhrlaub, {Jennifer L.} and Makiko Watanabe and Rachel Wong and Yvonne Castaneda and Pizzato, {Hannah A.} and Thompson, {Mallory R.} and Christine Bradshaw and Weinkauf, {Craig C.} and Christian Bime and Erickson, {Heidi L.} and Kenneth Knox and Billie Bixby and Sairam Parthasarathy and Sachin Chaudhary and Bhupinder Natt and Elaine Cristan and {El Aini}, Tammer and Franz Rischard and Janet Campion and Madhav Chopra and Michael Insel and Afshin Sam and Knepler, {James L.} and Capaldi, {Andrew P.} and Spier, {Catherine M.} and Dake, {Michael D.} and Taylor Edwards and Kaplan, {Matthew E.} and Scott, {Serena Jain} and Cameron Hypes and Jarrod Mosier and Harris, {David T.} and LaFleur, {Bonnie J.} and Ryan Sprissler and Janko Nikolich-{\v Z}ugich and Deepta Bhattacharya",
note = "Funding Information: The authors are indebted to the nurses in the intensive care units of Banner University Medical Center—Tucson and South Campuses and research coordinators (Cathleen Wilson and Trina Hughes) for facilitating the collection of samples in critically ill hospitalized patients with COVID-19. We thank F. Krammer, V. Simon, M. Rao, and J. Jhang at Mt. Sinai Hospital and A. Ellebedy and D. Fremont at Washington University in St. Louis for reagents and protocols. This work was supported in part by National Institutes of Health awards AG020719 and AG057701 and Centers for Disease Control and Prevention award 75D30120C08379 to J.N.-{\v Z}. the contract CTR050053 from the State of Arizona to J.N.-{\v Z}. and D.B. R01AI099108 and R01AI129945 to D.B. by the COVID-19 Rapid Response Grant from the UArizona BIO5 Institute to C.C.W. D.B. and J.N.-{\v Z}. and the Bowman Endowment in Medical Sciences to J.N.-{\v Z}. The graphical abstract for this study was created on biorender.com. T.J.R. J.L.U. M.W. R.W. R.S. J.N.{\v Z}. and D.B. designed the study. T.J.R. J.L.U. M.W. R.W. H.A.P. C.B. M.E.K. and R.S. performed experiments. T.J.R. J.L.U. M.W. R.W. A.P.C. C.M.S. M.E.K. T.E. R.S. J.N.{\v Z}. and D.B. analyzed the data. T.J.R. J.N.{\v Z}. and D.B. wrote the paper. All other authors participated in collection of samples and patient care for the study. Unrelated intellectual property of D.B. and Washington University has been licensed by Sana Biotechnology. J.N.{\v Z}. is on the scientific advisory board of and receives research funding from Young Blood, Inc. R.S. is a founder and chief scientific officer of Geneticure. R.W. is currently an employee of Vir Biotechnology. A provisional patent application related to this work has been filed with the US Patent Office. Funding Information: The authors are indebted to the nurses in the intensive care units of Banner University Medical Center—Tucson and South Campuses and research coordinators (Cathleen Wilson and Trina Hughes) for facilitating the collection of samples in critically ill hospitalized patients with COVID-19. We thank F. Krammer, V. Simon, M. Rao, and J. Jhang at Mt. Sinai Hospital and A. Ellebedy and D. Fremont at Washington University in St. Louis for reagents and protocols. This work was supported in part by National Institutes of Health awards AG020719 and AG057701 and Centers for Disease Control and Prevention award 75D30120C08379 to J.N.-{\v Z}., the contract CTR050053 from the State of Arizona to J.N.-{\v Z}. and D.B., R01AI099108 and R01AI129945 to D.B., by the COVID-19 Rapid Response Grant from the UArizona BIO5 Institute to C.C.W., D.B., and J.N.-{\v Z}., and the Bowman Endowment in Medical Sciences to J.N.-{\v Z}. The graphical abstract for this study was created on biorender.com . Funding Information: Unrelated intellectual property of D.B. and Washington University has been licensed by Sana Biotechnology. J.N.{\v Z}. is on the scientific advisory board of and receives research funding from Young Blood, Inc. R.S. is a founder and chief scientific officer of Geneticure. R.W. is currently an employee of Vir Biotechnology. A provisional patent application related to this work has been filed with the US Patent Office. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = nov,
day = "17",
doi = "10.1016/j.immuni.2020.10.004",
language = "English (US)",
volume = "53",
pages = "925--933.e4",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "5",
}