Performance and health economic evaluation of the Mount Sinai COVID 19 serological assay identifies modification of thresholding as necessary to maximise specificity of the assay

We evaluated the FDA approved SARS-CoV-2 immunoassay (developed at Mount Sinai, by Krammer and colleagues) for the identification of COVID-19 seroconversion and potential cross-reactivity of the assay in a United Kingdom (UK) National Health Service (NHS) hospital setting. In our ‘set up’ cohort we found that the SARS-CoV-2 IgG was detectable in 100% of patients tested 14 days post positive COVID-19 nucleic acid test. Serum samples taken from pregnant women in 2018 were used as a negative control group with zero false positives. We also analysed samples from patients with non-COVID-19 viral infections, paraproteinaemia or autoantibodies and found false positive results in 6/179. Modification of the sensitivity threshold to five standard deviations from the mean of the control group eliminated all false positive result in the ‘set up’ cohort. We confirmed the validity of the test with a revised threshold on an independent prospective ‘validation cohort’ of patient samples. Taking data from both cohorts we report a sensitivity of the Mount Sinai assay of 96.6% (28/29) and specificity of 100% (299/299) using a revised threshold cut-off, at a time point at least 14 days since the diagnostic antigen test. Finally, we conducted a health economic probabilistic sensitivity analysis (PSA) on the costs of producing the tests, and the mean cost we estimate to be 13.63 pounds sterling (95%CI 9.63 - 18.40), allowing its cost effectiveness to be tested against other antibody tests. In summary, we report that the Mount Sinai IgG ELISA assay is highly sensitive test for SARS-Cov-2 infection, however modification of thresholding was required to minimise false positive results. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement J.G.W.S. is supported by the Academy of Medical Sciences/the Wellcome Trust/ the Government Department of Business, Energy and Industrial Strategy/the British Heart Foundation/Diabetes UK Springboard Award [SBF005\1057]. S.A.R is funded by The Rosetrees Trust and the Big C charity ### 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: Faculty of Medicine and Health Sciences Research Ethics Committee, Norwich Medical School, University of East Anglia 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 The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.