Rapid generation of neutralizing antibody responses in COVID-19 patients

Suthar, Mehul S.; Zimmerman, Matthew G.; Kauffman, Robert C.; Mantus, Grace; Linderman, Susanne L.; Hudson, William H.; Vanderheiden, Abigail; Nyhoff, Lindsay; Davis, Carl W.; Adekunle, Seyi; Affer, Maurizio; Sherman, Melanie; Reynolds, Stacian; Verkerke, Hans P.; Alter, David N.; Guarner, Jeannette; Bryksin, Janetta; Horwath, Michael; Arthur, Connie M.; Saakadze, Natia; Smith, Geoffrey Hughes; Edupuganti, Srilatha; Scherer, Erin M.; Hellmeister, Kieffer; Cheng, Andrew; Morales, Juliet A.; Neish, Andrew S.; Stowell, Sean R.; Frank, Filipp; Ortlund, Eric; Anderson, Evan; Menachery, Vineet D.; Rouphael, Nadine; Mehta, Aneesh; Stephens, David S.; Ahmed, Rafi; Roback, John D.; Wrammert, Jens

Summary SARS-CoV-2, the virus responsible for COVID-19, is causing a devastating global 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.