@article{5fb76f42435f4f2ab0f26abce1be103c,
title = "Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients",
abstract = "SARS-CoV-2, the virus responsible for COVID-19, is causing a devastating worldwide pandemic, and there is a pressing need to understand the development, specificity, and neutralizing potency of humoral immune responses during acute infection. We report a cross-sectional study of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in a cohort of 44 hospitalized COVID-19 patients. RBD-specific IgG responses are detectable in all patients 6 days after PCR confirmation. Isotype switching to IgG occurs rapidly, primarily to IgG1 and IgG3. Using a clinical SARS-CoV-2 isolate, neutralizing antibody titers are detectable in all patients by 6 days after PCR confirmation and correlate with RBD-specific binding IgG titers. The RBD-specific binding data were further validated in a clinical setting with 231 PCR-confirmed COVID-19 patient samples. These findings have implications for understanding protective immunity against SARS-CoV-2, therapeutic use of immune plasma, and development of much-needed vaccines.",
keywords = "COVID-19, SARS-CoV-2, coronavirus, humoral immune response, neutralizing antibody, protective immunity, receptor-binding protein, serology test, spike protein",
author = "Suthar, {Mehul S.} and Zimmerman, {Matthew G.} and Kauffman, {Robert C.} and Grace Mantus and Linderman, {Susanne L.} and Hudson, {William H.} and Abigail Vanderheiden and Lindsay Nyhoff and Davis, {Carl W.} and Oluwaseyi Adekunle and Maurizio Affer and Melanie Sherman and Stacian Reynolds and Verkerke, {Hans P.} and Alter, {David N.} and Jeannette Guarner and Janetta Bryksin and Horwath, {Michael C.} and Arthur, {Connie M.} and Natia Saakadze and Smith, {Geoffrey H.} and Srilatha Edupuganti and Scherer, {Erin M.} and Kieffer Hellmeister and Andrew Cheng and Morales, {Juliet A.} and Neish, {Andrew S.} and Stowell, {Sean R.} and Filipp Frank and Eric Ortlund and Anderson, {Evan J.} and Menachery, {Vineet D.} and Nadine Rouphael and Mehta, {Aneesh K.} and Stephens, {David S.} and Rafi Ahmed and Roback, {John D.} and Jens Wrammert",
note = "Funding Information: We would like to thank Laurel Bristow, Ariel Kay, Youssef Saklawi, Ghina Alaaeddine, Nina McNair, Ellie Butler, Brandi Johnson, Christopher Huerta, Jennifer Kleinhenz, Vinit Karmali, Yong Xu, Dongli Wang, and Michele McCullough for sample processing at the Hope Clinic. We also acknowledge the dedicated efforts of Hassan Bilal, DeAndre Brown, Davette Campbell, Lisa Cole, Ginger Crews, Shanessa Fakour, Natalie Hicks, Mark Meyers, and Katherine Normile for sample collection, processing, and organization. We thank Gabrielle Holenstein, Corin Jones, Alethea Luo-Gardner, Hoa Nguyen, Keyanna Seville, and Corazon Tomblin for the exceptional technical performance of the ELISA at the Emory Medical Laboratories. We also acknowledge thorough and rapid chart reviews by Kari Broder. We thank Guido Silvestri for helpful discussions. We thank Michael Konomos for help with generating the graphical abstract. Finally, we thank all the participating patients and the hospital staff caring for them. This work was funded in part by an Emory EVPHA Synergy Fund award (M.S.S. and J.W.), and by the National Institutes of Health NIAID Infectious Diseases Clinical Research Consortium (IDCRC) UM1 AI148684 (D.S.S. R.A. and J.W), R01 AI137127 (J.W.), ORIP/OD P51OD011132 (M.S.S.), 5T32 AI074492 (S.L.L.), R00 AG049092 (V.D.M.), World Reference Center for Emerging Viruses and Arboviruses R24 AI120942 (V.D.M.), HIPC 5U19AI090023-10 (N.R. E.A. and A.M.), VTEU 1UM1AI148576-01 (E.A. and N.R.), and a grant from The Marcus Foundation (J.D.R). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. M.S. S.R. H.P.V. D.N.A. J.G. G.M. S.L. and A.V. contributed to the acquisition, analysis, and interpretation of the data, J.B. and M.C.H. contributed to the acquisition and interpretation of the data, C.M.A. and N.S. contributed to the acquisition of the data, G.H.S. M.G.Z. and R.C.K. contributed to the acquisition, analysis, and interpretation of the data and helped draft the work, A.K.M. A.S.N. and S.R.S. contributed to the acquisition, analysis, and interpretation of the data, as well as the conception and design of the work, D.S.S. L.N. S.A. M.A. W.H.H. C.W.D. and V.D.M. contributed to the analysis, and interpretation of the data, S.E. served as the principal investigator of the clinical protocol for acquisition of patient samples and contributed to the interpretation of data, E.M.S. K.H. A.C. J.A.M. N.R. and E.J.A. contributed to the acquisition and interpretation of the data, and J.D.R. R.A. J.W. and M.S.S. contributed to the acquisition, analysis, and interpretation of the data, as well as the conception and design of the work, and writing the manuscript. The authors declare no competing interests. Funding Information: We would like to thank Laurel Bristow, Ariel Kay, Youssef Saklawi, Ghina Alaaeddine, Nina McNair, Ellie Butler, Brandi Johnson, Christopher Huerta, Jennifer Kleinhenz, Vinit Karmali, Yong Xu, Dongli Wang, and Michele McCullough for sample processing at the Hope Clinic. We also acknowledge the dedicated efforts of Hassan Bilal, DeAndre Brown, Davette Campbell, Lisa Cole, Ginger Crews, Shanessa Fakour, Natalie Hicks, Mark Meyers, and Katherine Normile for sample collection, processing, and organization. We thank Gabrielle Holenstein, Corin Jones, Alethea Luo-Gardner, Hoa Nguyen, Keyanna Seville, and Corazon Tomblin for the exceptional technical performance of the ELISA at the Emory Medical Laboratories. We also acknowledge thorough and rapid chart reviews by Kari Broder. We thank Guido Silvestri for helpful discussions. We thank Michael Konomos for help with generating the graphical abstract. Finally, we thank all the participating patients and the hospital staff caring for them. This work was funded in part by an Emory EVPHA Synergy Fund award (M.S.S. and J.W.), and by the National Institutes of Health NIAID Infectious Diseases Clinical Research Consortium (IDCRC) UM1 AI148684 (D.S.S., R.A., and J.W), R01 AI137127 (J.W.), ORIP/OD P51OD011132 (M.S.S.), 5T32 AI074492 (S.L.L.), R00 AG049092 (V.D.M.), World Reference Center for Emerging Viruses and Arboviruses R24 AI120942 (V.D.M.), HIPC 5U19AI090023-10 (N.R., E.A., and A.M.), VTEU 1UM1AI148576-01 (E.A. and N.R.), and a grant from The Marcus Foundation (J.D.R) . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = jun,
day = "23",
doi = "10.1016/j.xcrm.2020.100040",
language = "English (US)",
volume = "1",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "3",
}