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