Suggested new breakpoints of anti-MERS-CoV antibody ELISA titers: performance analysis of serologic tests
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To provide optimal cut-off values of anti-Middle East respiratory syndrome coronavirus (MERS-CoV) serologic tests, we evaluated performance of ELISA IgG, ELISA IgA, IFA IgM, and IFA IgG using 138 serum samples of 49 MERS-CoV-infected patients and 219 serum samples of 219 rRT-PCR-negative MERS-CoV-exposed healthcare personnel and patients. The performance analysis was conducted for two different purposes: (1) prediction of neutralization activity in MERS-CoV-infected patients, and (2) epidemiologic surveillance of MERS-CoV infections among MERS-CoV-exposed individuals. To evaluate performance according to serum collection time, we used ‘days post onset of illness (dpoi)’ and ‘days post exposure (dpex)’ assessing neutralization activity and infection diagnosis, respectively. Performance of serologic tests improved with delayed sampling time, being maximized after a seroconversion period. In predicting neutralization activity, ELISA IgG tests showed optimal performance using sera collected after 21 dpoi at cut-off values of OD ratio 0.4 (sensitivity 100% and specificity 100%), and ELISA IgA showed optimal performance using sera collected after 14 dpoi at cut-off value of OD ratio 0.2 (sensitivity 85.2% and specificity 100%). In diagnosis of MERS-CoV infection, ELISA IgG exhibited optimal performance using sera collected after 28 dpex, at a cut-off value of OD ratio 0.2 (sensitivity 97.3% and specificity 92.9%). These new breakpoints are markedly lower than previously suggested values (ELISA IgG OD ratio 1.1, sensitivity 34.8% and specificity 100% in the present data set), and the performance data help serologic tests to be practically used in the field of MERS management.
KeywordsMiddle East respiratory syndrome coronavirus Serology Antibody Sensitivity Specificity
We would like to express our sincerest condolences to the patients and families who suffered from the MERS outbreak. We also greatly appreciate the HCP and staff members at Samsung Medical Center and all other hospitals who worked together to overcome the MERS outbreak. Finally, we would like to thank Jinseob Kim for statistical advice and figure development, as well as Mingu Kang for IFA testing.
Compliance with ethical standards
This work was supported by a Samsung Biomedical Research Institute (SBRI) grant [#SMX1161321]. CD reports funding by EU grants Antigone (GA no. 278976) and Prepare (GA no. 602525).
Conflicts of interest
There are no potential conflicts of interest relevant to this article to report.
This study was approved by the Institutional Review Board of Samsung Medical Center.
As a retrospective study, the Institutional Review Board waived informed consent in the present study.
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