Comparison of Serologic Assays for Middle East Respiratory Syndrome Coronavirus

Ruth Harvey; Giada Mattiuzzo; Mark Hassall; Andrea Sieberg; Marcel A. Müller; Christian Drosten; Peter Rigsby; Christopher J. Oxenford; study participants

Disclosures

Emerging Infectious Diseases. 2019;25(10):1878-1883. 

In This Article

Abstract and Introduction

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) was detected in humans in 2012. Since then, sporadic outbreaks with primary transmission through dromedary camels to humans and outbreaks in healthcare settings have shown that MERS-CoV continues to pose a threat to human health. Several serologic assays for MERS-CoV have been developed globally. We describe a collaborative study to investigate the comparability of serologic assays for MERS-CoV and assess any benefit associated with the introduction of a standard reference reagent for MERS-CoV serology. Our study findings indicate that, when possible, laboratories should use a testing algorithm including ≥2 tests to ensure correct diagnosis of MERS-CoV. We also demonstrate that the use of a reference reagent greatly improves the agreement between assays, enabling more consistent and therefore more meaningful comparisons between results.

Introduction

Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012,[1] more than 2,250 laboratory-confirmed cases have been reported to the World Health Organization (WHO); approximately one third of these cases were fatal. A large proportion of MERS-CoV cases have been the result of human-to-human transmission in healthcare settings;[2,3] outbreaks have occurred in several countries, with the largest outbreaks seen in Saudi Arabia, United Arab Emirates, and South Korea.[4] Dromedary camels are the putative reservoir hosts for MERS-CoV; they experience no or mild symptoms upon infection.[5] Primary infection can occur from dromedary camels to humans, and new cases with evidence of camel contact continue to occur sporadically.[6] MERS-CoV is 1 of the 10 high-threat pathogens on the WHO Research and Development Blueprint,[7] a document that sets out a roadmap for research and development of diagnostics, preventive and therapeutic products for prevention, and early detection and response to these high-priority pathogens. The WHO roadmap for MERS-CoV lists several priority activities, including improved diagnostics and vaccines for humans and camels as well as basic and translational research.[8] Serologic assays are critical for the evaluation of the efficacy of new vaccines and patient treatment, as are diagnostic tools to confirm infections and perform serosurveillance. A variety of serologic assays have been developed globally, both commercially and in-house; however, there is no evidence supporting the quality of performance of these assays and their consistency with one another. Participants at the WHO intercountry meeting on MERS-CoV in Cairo, Egypt, June 20–22, 2013, recognized this issue as a public health priority and called for a study to compare currently available serologic assays.[9] Therefore, we assembled a panel of human serum or plasma and polyclonal antibodies to compare the performance of serologic assays for MERS-CoV. We invited participants to use their testing algorithms to diagnose each sample as if it were a real patient sample. The assays were evaluated for sensitivity and specificity. Pas et al. described in 2015 the impact that a single international standard would have on reducing interlaboratory variability for MERS-CoV diagnostics (albeit in this case for NAT assays).[10] To this end, we included 2 samples in the panel as examples of potential WHO International Standard material, and we assessed their effectiveness in harmonization of the data from the participant laboratories.

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