Cell https://doi.org/10.1016/j.cell.2021.05.032 (2021)

Antibodies against viruses are not always protective. In Cell, Arase and colleagues identify Abs against SARS-CoV-2 that bind the N-terminal domain (NTD) of the spike (S) protein and induce an open conformation of the receptor-binding domain (RBD), which results in enhanced binding to the virus receptor ACE2 and enhanced infectivity. In a screen of Abs isolated from patients with COVID-19, some of the Abs to NTD enhance the binding of S protein to ACE2 to a level higher than that of the D614G mutant S protein, which is known to have an open RBD conformation. All enhancing Abs bind the same sites (W64, H66, V213 and R214) in the S protein, dock similarly on the NTD and induce the open RBD state. Enhancing Abs reduce the neutralizing capacity of neutralizing Abs. Patients with COVID-19 have both enhancing and neutralizing Abs, and the difference between enhancing and neutralizing titers is greater in patients with severe as compared to non-severe disease.