Abstract: Methods of detecting SARS-CoV-2 antibodies with improved specificity are described. The methods can include contacting a sample potentially containing SARS-CoV-2 antibodies with a reagent to remove non-anti-SARS-CoV-2 antibodies, such as a reagent comprising an epitope from a nucleocapsid protein or spike protein of a common coronavirus. The methods can include contacting the sample with a mutant SARS-CoV-2 nucleocapsid protein or spike protein comprising a reduced number of common coronavirus epitopes. The methods can involve comparing results from an immunoassay performed with a SARS-CoV-2 protein to results obtained from immunoassays performed with analogous protein from one or more common coronaviruses.