Antibodies are a potential therapy for severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them
remains unclear. Here we map how all mutations to the receptor binding domain
(RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and
the antibody LY-CoV016. These complete maps uncover a single amino acid mutation
that fully escapes the REGN-COV2 cocktail, which consists of two antibodies,
REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also
identify viral mutations that are selected in a persistently infected patient
treated with REGN-COV2 and during in vitro viral escape selections. Finally, the
maps reveal that mutations escaping the individual antibodies are already present
in circulating SARS-CoV-2 strains. These complete escape maps enable
interpretation of the consequences of mutations observed during viral
surveillance.