Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection

Anderson, Elizabeth M.; Goodwin, Eileen C.; Verma, Anurag; Arevalo, Claudia P.; Bolton, Marcus J.; Weirick, Madison E.; Gouma, Sigrid; McAllister, Christopher M.; Christensen, Shannon R.; Weaver, JoEllen; Hicks, Philip; Manzoni, Tomaz B.; Oniyide, Oluwatosin; Ramage, Holly; Mathew, Divij; Baxter, Amy E.; Oldridge, Derek A.; Greenplate, Allison R.; Wu, Jennifer E.; Alanio, Cécile; D’Andrea, Kurt; Kuthuru, Oliva; Dougherty, Jeanette; Pattekar, Ajinkya; Kim, Justin; Han, Nicholas; Apostolidis, Sokratis A.; Huang, Alex C.; Vella, Laura A.; Kuri-Cervantes, Leticia; Pampena, M. Betina; Betts, Michael R.; Wherry, E. John; Meyer, Nuala J.; Cherry, Sara; Bates, Paul; Rader, Daniel J.; Hensley, Scott E.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread within the human population. Although SARS-CoV-2 is a novel coronavirus, most humans had been previously exposed to other antigenically distinct common seasonal human coronaviruses (hCoVs) before the COVID-19 pandemic. Here, we quantified levels of SARS-CoV-2-reactive antibodies and hCoV-reactive antibodies in serum samples collected from 431 humans before the COVID-19 pandemic. We then quantified pre-pandemic antibody levels in serum from a separate cohort of 251 individuals who became PCR-confirmed infected with SARS-CoV-2. Finally, we longitudinally measured hCoV and SARS-CoV-2 antibodies in the serum of hospitalized COVID-19 patients. Our studies indicate that most individuals possessed hCoV-reactive antibodies before the COVID-19 pandemic. We determined that ∼20% of these individuals possessed non-neutralizing antibodies that cross-reacted with SARS-CoV-2 spike and nucleocapsid proteins. These antibodies were not associated with protection against SARS-CoV-2 infections or hospitalizations, but they were boosted upon SARS-CoV-2 infection.