Manufacturer Signal-to-Cutoff Threshold Underestimates Cumulative Incidence of SARS-CoV-2 Infection: Evidence from the Los Angeles Firefighters Study.

Autor:	Toubat O; Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA., Berg AH; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Sobhani K; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Mulligan K; Schaeffer Center for Health Policy and Economics, Department of Health Policy and Management, Sol Price School of Public Policy, University of Southern California, Los Angeles, CA, USA., Hori AM; Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Bhattacharya J; Center for Health Policy/Primary Care and Outcomes Research, Department of Medicine, Stanford University, Stanford, CA, USA., Sood N; Schaeffer Center for Health Policy and Economics, Department of Health Policy and Management, Sol Price School of Public Policy, University of Southern California, Los Angeles, CA, USA.
Jazyk:	angličtina
Zdroj:	The journal of applied laboratory medicine [J Appl Lab Med] 2022 Sep 01; Vol. 7 (5), pp. 1169-1174.
DOI:	10.1093/jalm/jfac034
Abstrakt:	Background: The objective of this analysis was to compare the performance sensitivity and specificity of manufacturer-recommended signal-to-cutoff (S/Co) thresholds with modified S/Co values to estimate the prevalence of SARS-CoV-2-specific antibodies in a cohort of firefighters with a known infection history. Methods: Plasma venipuncture samples were used for serologic analysis of firefighters in Los Angeles, CA, USA, in October 2020. Seropositivity was assessed using the manufacturer's recommended S/Co (≥1.4 IgG) and modified S/Co thresholds based on measured antibody levels in 178 negative control patients who had blood drawn prior to the emergence of COVID-19. Optimal S/Co threshold was determined by receiver operating characteristic (ROC) curve analysis. Results: Of 585 firefighters included in the study, 52 (8.9%) reported having a PCR-positive test history prior to antibody testing. Thirty-five (67.3%) firefighters with a previous PCR-positive test were seropositive based on the manufacturer S/Co thresholds, consistent with an estimated 67.3% sensitivity and 100% specificity. After evaluating multiple modified S/Co thresholds based on pre-pandemic negative samples, a modified S/Co of 0.36 was found to yield optimal sensitivity (88.5%) and specificity (99.4%) by ROC curve analysis. This modified threshold improved serostatus classification accuracy by 21.2%. Conclusions: S/Co thresholds based on known negative samples significantly increase seropositivity and more accurately estimate cumulative incidence of disease compared to manufacturer-based thresholds. Competing Interests: Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest: Employment or Leadership: None declared. Consultant or Advisory Role: N. Sood, Payssurance and American Medical Association. Stock Ownership: None declared. Honoraria: None declared. Research Funding: O. Toubat is supported in part by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number F30HL154324 outside of the submitted work. A.H. Berg is supported in part by grants from the National Institutes of Health outside of the submitted work. J. Bhattacharya is supported in part by grants from the National Institutes of Health outside of the submitted work. N. Sood received funding and in-kind support from the Burns and Allen Research Institute at Cedars-Sinai Medical Center, Mayor’s Office City of Los Angeles, Rockefeller Foundation, Abbott Diagnostics, and the Conrad R. Hilton Foundation for the study, and grants from the Agency for Healthcare Research and Quality, the National Institutes of Health, Health Care Services Corporation, and the Patient-Centered Outcomes Research Institute outside the submitted work. Expert Testimony: None declared. Patents: None declared. Other Remuneration: K. Mulligan, personal fees from Precision Health Economics; N. Sood, personal fees from the China Development Research Foundation, PhRMA, MDL law firms, Precision Health Economics, and H&H Wholesale; J. Bhattacharya, personal fees from Acumen LLC. (© American Association for Clinical Chemistry 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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