Expanding covid-19 vaccine availability: Role for combined orthogonal serology testing (cost)

Madhusudhanan Narasimhan, Lenin Mahimainathan, Ellen Araj, Andrew E. Clark, Kathleen Wilkinson, Sruthi Yekkaluri, Jasmin Tiro, Francesca M. Lee, Jyoti Balani, Ravi Sarode, Amit G. Singal, Alagarraju Muthukumar

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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 (IgGNC) 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 IgGNC to determine the prevalence. We used 614 prospective study subjects to assess the utility of COST (IgGNC, IgM-spike (IgMSP), and IgG-spike (IgGSP)) 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 IgGNC serology performed. Prospectively, IgGNC serology identified twice the number of COVID-positive cases in relation to RT-PCR alone. COST further increased the number of detected positive cases: IgGNC+ or IgMSP+ (18.0%); IgGNC+ or IgGSP+ (23.5%); IgMSP+ or IgGSP+ (23.8%); and IgGNC+ or IgMSP+ or IgGSP+ (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.

Original languageEnglish (US)
Article number376
Issue number4
StatePublished - Apr 2021


  • COVID-19
  • IgG
  • IgM
  • Nucleocapsid
  • Orthogonal antibody testing
  • SARS-CoV-2
  • Spike
  • Vaccine
  • Vaccine prioritization

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)


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