Expanding COVID-19 Vaccine Availability: Role for Combined Orthogonal Serology Testing (COST)

The persisting Coronavirus disease 2019 (COVID-19) pandemic and limited vaccine supply has led to a shift in global health priorities to expand vaccine coverage. Relying on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular testing alone cannot reveal the infection proportion, which could play a critical role in vaccination prioritization. We evaluated the utility of a combination orthogonal serological testing (COST) algorithm alongside RT-PCR to quantify prevalence with the aim of identifying candidate patient clusters to receive single and/or delayed vaccination. We utilized 108,505 patients with suspected COVID-19 in a retrospective analysis of SARS-CoV-2 RT-PCR vs. IgG-nucleocapsid (IgG ) antibody testing coverage in routine practice for the estimation of prevalence. Prospectively, an independent cohort of 21,388 subjects was simultaneously tested by SARS-CoV-2 RT-PCR and IgG to determine the prevalence. We used 614 prospective study subjects to assess the utility of COST (IgG , IgM-spike (IgM ), and IgG-spike (IgG )) in establishing the infection proportion to identify a single-dose vaccination cohort. Retrospectively, we observed a 6.3% (6871/108,505) positivity for SARS-CoV-2 RT-PCR, and only 2.3% (2533/108,505) of cases had paired IgG serology performed. Prospectively, IgG serology identified twice the number of COVID-positive cases in relation to RT-PCR alone. COST further increased the number of detected positive cases: IgG + or IgM + (18.0%); IgG + or IgG + (23.5%); IgM + or IgG + (23.8%); and IgG + or IgM + or IgG + (141/584 = 24.1%). COST may be an effective tool for the evaluation of infection proportion and thus could define a cohort for a single dose and/or delayed vaccination.