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

Background: 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. Methods: We utilized 108,505 patients with suspected COVID-19 in a retrospective analysis of SARS-CoV-2 RT-PCR vs. IgG-nucleocapsid (IgG(NC)) 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(NC) to determine the prevalence. We used 614 prospective study subjects to assess the utility of COST (IgG(NC), IgM-spike (IgM(SP)), and IgG-spike (IgG(SP))) in establishing the infection proportion to identify a single-dose vaccination cohort. Results: 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(NC) serology performed. Prospectively, IgG(NC) 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(NC)+ or IgM(SP)+ (18.0%); IgG(NC)+ or IgG(SP)+ (23.5%); IgM(SP)+ or IgG(SP)+ (23.8%); and IgG(NC)+ or IgM(SP)+ or IgG(SP)+ (141/584 = 24.1%). Conclusion: 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.