Comparable diagnostic accuracy of SARS-CoV-2 Spike RBD and N-specific IgG tests to determine pre-vaccination nation-wide baseline seroprevalence in Mexico

A major challenge for developing countries during the COVID-19 pandemic is affordable and adequate monitoring of disease progression and population exposure as the primary source relevant epidemiological indicators. Serology testing enables assessing population exposure and to guide vaccination strategies but requires rigorous accuracy validation before population-wide implementation. We adapted a two-step ELISA protocol as a single-step protocol for detection of IgG against the Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein and compared its diagnostic accuracy with a commercial immunoassay anti-nucleoprotein IgG. Both methods yielded adequate and comparable diagnostic accuracy after 3 weeks post-symptom onset and were implemented in a nation-wide population based serological survey during August–November 2020. Anti-RBD National seroprevalence was 23.6%, 1.3% lower, but not significantly, than for anti-N. Double positive seroprevalence was 19.7%. Anti-N single-positive seroprevalence was 3.72% and anti-RBD single-positive seroprevalence was 1.98%. Discrepancies in the positivity to either single marker may be due to different kinetics of each antibody marker as well as the heterogeneity of the sampling time in regards to local epidemic waves. Baseline single positivity prevalence will be useful to assess the serological impact of vaccination and natural infection in further serosurveillance efforts.