Sensitive and Specific Detection of Low-Level Antibody Responses in Mild Middle East Respiratory Syndrome Coronavirus Infections

Okba, Nisreen M.A.; Raj, V. Stalin; Widjaja, Ivy; GeurtsvanKessel, Corine H.; de Bruin, Erwin; Chandler, Felicity D.; Park, Wan Beom; Kim, Nam-Joong; Farag, Elmoubasher A.B.A.; Al-Hajri, Mohammed; Bosch, Berend-Jan; Oh, Myoung-don; Koopmans, Marion P.G.; Reusken, Chantal B.E.M.; Haagmans, Bart L.

Middle East respiratory syndrome coronavirus (MERS-CoV) infections in humans can cause asymptomatic to fatal lower respiratory lung disease. Despite posing a probable risk for virus transmission, asymptomatic to mild infections can go unnoticed; a lack of seroconversion among some PCR-confirmed cases has been reported. We found that a MERS-CoV spike S1 protein–based ELISA, routinely used in surveillance studies, showed low sensitivity in detecting infections among PCR-confirmed patients with mild clinical symptoms and cross-reactivity of human coronavirus OC43–positive serum samples. Using in-house S1 ELISA and protein microarray, we demonstrate that most PCR-confirmed MERS-CoV case-patients with mild infections seroconverted; nonetheless, some of these samples did not have detectable levels of virus-neutralizing antibodies. The use of a sensitive and specific serologic S1-based assay can be instrumental in the accurate estimation of MERS-CoV prevalence.