SARS-CoV-2 infection results in antibody development against viral proteins, including the N and S proteins. Vaccine-induced antibody development has implications for antibody testing.
Before vaccine availability, a SARS-CoV-2 antibody test that detects any of the N, S, or RBD antibodies could indicate previous exposure to SARS-CoV-2. A vaccinated person could test positive by serologic testing for the vaccine antigenic target S and S subunits, including RBD, but not against other non-target proteins.
A history of vaccination and/or prior SARS-CoV-2 infection must be considered when interpreting antibody test results. Available antibody tests for SARS-CoV-2 assess IgM and/or IgG to one of two virus proteins: S or N. SARS-CoV-2 vaccines encode for the spike protein or a portion of the protein. A positive laboratory test for S IgM and/or IgG could indicate prior infection and/or vaccination. Evidence of previous SARS-CoV-2 infection in a patient with a history of immunization can be evaluated with specific testing for Anti-N IgM/IgG. Although current Emergency Use Authorized (EUA) approved assays do not preclude the use of anti-N IgM/IgG testing, none of the approved assays have been specifically authorized to assess the immunity or protection of persons who have been vaccinated against COVID-19.26
