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Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients

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Suthar, Mehul S., Matthew G. Zimmerman, Robert C. Kauffman, Grace Mantus, Susanne L. Linderman, William H. Hudson, Abigail Vanderheiden, Lindsay Nyhoff, Carl W. Davis, Oluwaseyi Adekunle, Maurizio Affer, Melanie Sherman, Stacian Reynolds, Hans P. Verkerke, David N. Alter, Jeannette Guarner, Janetta Bryksin, Michael C. Horwath, Connie M. Arthur, Natia Saakadze, Geoffrey H. Smith, Srilatha Edupuganti, Erin M. Scherer, Kieffer Hellmeister, Andrew Cheng, Juliet A. Morales, Andrew S. Neish, Sean R. Stowell, Filipp Frank, Eric Ortlund, Evan J. Anderson, Vineet D. Menachery, Nadine Rouphael, Aneesh K. Mehta, David S. Stephens, Rafi Ahmed, John D. Roback, and Jens Wrammert. 2020. "Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients." Cell Reports Medicine 1 (3):100040-.

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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, neutralizing antibody, spike protein, receptor-binding protein, coronavirus, protective immunity, serology test, humoral immune response

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