Performance of Abbott Architect, Ortho Vitros, and Euroimmun Assays in Detecting Prior SARS CoV 2 Infection

Background Several serological assays have been developed to detect anti-SARS-CoV-2 IgG antibodies, but evidence about their comparative performance is limited. We sought to assess the sensitivity of four anti-SARS-CoV-2 IgG enzyme-linked immunosorbent assays (ELISA) in individuals with evidence of prior SARS-CoV-2 infection. Methods We obtained sera from 36 individuals with PCR-confirmed SARS-CoV-2 infection between March and May 2020. We evaluated samples collected at around 21 days (±14 days) after their initial PCR test using 3 commercially available ELISA assays, two anti-spike (Ortho- Clinical Diagnostics Vitros, and Euroimmun) and one anti-nucleocapsid (Abbott Architect), and a Yale-developed anti-spike ELISA test. We determined the sensitivity of the tests and compared their results. The Euroimmun and Yale ELISA had an equivocal and indeterminate category, which were considered as both negative and positive. Results Among the 36 individuals with SARS-CoV-2 infection, mean age was 43 (±13) years and 19 (53%) were female. The sensitivities of the tests were not significantly different (Abbott Architect, Ortho Vitros, Euroimmmun, and Yale assays: 86% (95% confidence interval [CI], 71– 95), 94% (95% CI, 81–99), 86% (95% CI, 71–95), and 94% (95% CI, 81–99), respectively; p- value=0.464). The sensitivities of the Euroimmun and Yale ELISA tests increased when the equivocal/indeterminate results were considered positive (97% [95% CI, 85–100] and 100% [95% CI, 90–100], respectively), but were not significantly different from other tests (p=0.082). The cross-correlation coefficient ranged from 0.85–0.98 between three anti-spike protein assays (Ortho Vitros, Euroimmun, Yale) and was 0.58–0.71 between the three anti-spike protein assays and the anti-nucleocapsid assay (Abbott). Conclusion The sensitivities of four anti-SARS-CoV-2 protein assays did not significantly differ, although the sample size was small. Sensitivity also depended on the interpretation of equivocal and indeterminate results. The strongest correlations were present for the three anti- spike proteins assays. These findings suggest that individual test characteristics and the correlation between different tests should be considered when comparing or aggregating data across different populations studies for serologic surveillance of past SARS-CoV-2 infection. ### Competing Interest Statement Dr. Krumholz works under contract with the Centers for Medicare & Medicaid Services to support quality measurement programs; was a recipient of a research grant, through Yale, from Medtronic and the United States Food and Drug Administration to develop methods for post-market surveillance of medical devices; was a recipient of a research grant with Medtronic and is the recipient of a research grant from Johnson & Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation, from the Ben C. Martin Law Firm for work related to the Cook Celect IVC filter litigation, and from the Siegfried and Jensen Law Firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a participant/participant representative of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook, and the Physician Advisory Board for Aetna; and is a co-founder of HugoHealth, a personal health information platform, and co-founder of Refactor Health, an enterprise healthcare artificial intelligence-augmented data management company. The other co-authors report no potential competing interests. ### Funding Statement None ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Board at Yale University All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data referred to in the manuscript can be made available on request.