Analytical and diagnostic performances of a high-throughput immunoassay for SARS-CoV-2 IgM and IgG

Abstract

BackgroundAbstractReliable SARS-CoV-2 serological assays are required for diagnosing infections, for the serosurveillance of past exposures and for assessing the response to future vaccines. In this study, the analytical and clinical performances of a chemiluminescent immunoassays for SARS-CoV-2 IgM and IgG detection (Mindray CL-1200i), targeting Nucleocapsid (N) and receptor binding domain (RBD) portion of the Spike protein, were evaluated.MethodsPrecision and linearity were evaluated using standardized procedures. A total of 157 leftover serum samples from 81 hospitalized confirmed COVID-19 patients (38 with moderate and 43 with severe disease) and 76 SARS-CoV-2 negative subjects (44 healthcare workers, 20 individuals with rheumatic disorders, 12 pregnant women) were included in the study. In an additional series of 44 SARS-CoV-2 positive, IgM and IgG time kinetics were also evaluated in a time-period of 38 days.ResultsPrecision was below or equal to 4% for both IgM and IgG, in all the studied levels, whilst a slightly significant deviation from linearity was observed for both assays in the range of values covering the manufacturer’s cut-off. Considering a time frame ≥ 12 days post symptom onset, sensitivity and specificity for IgM were 92.3% (95%CI:79.1%-98.4%) and 92.1% (95%CI:83.6%-97.0%). In the same time frame, sensitivity and specificity for IgG were 100% (95%CI:91.0%-100%) and 93.4% (95%CI:85.3%-97.8%). The assays agreement was 73.9% (Cohen’s kappa of 0.373). Time kinetics showed a substantial overlapping of IgM and IgG response, the latter values being elevated up to 38 days from symptoms onset.ConclusionsAnalytical imprecision is satisfactory as well as the linearity, particularly when taking into account the fact that both assays are claimed to be qualitative. Diagnostic sensitivity of IgG was excellent, especially considering specimens collected ≥12 days post symptom onset. Time kinetics suggest that IgM and IgG are detectable early in the course of infection, but the role of SARS-CoV-2 antibodies in clinical practice still requires further evaluations.

SARS-CoV2 serology assays: utility and limits of different antigen based tests through the evaluation and the comparison of four commercial tests

“…Regarding the specificity, Vidas®IgM and Mindray®IgM and IgG tests gave positive signals for few pre-pandemic sera and this was also reported by other authors (31,33,34). Cross reactivity with pre-pandemic auto-immune disease patients sera was previously reported(37).…”

“…Third is the ECLIA Elecsys® technology developed by Roche® which is highly efficient regardless of the measured analyte (29,30). For the other tests, such (33,34). This new version of Mindray® was not available at the study writing time and merits to be evaluated.…”

“…Similar low sensitivities for the Vidas® test were reported by Younes et al (88,3 for Vidas®IgG after D21) and by Wolf et al (over all sensitivity of 64,9%CI95%[55,2-73,7] for Vidas®IgM and 73%CI95%[63,7-81] for Vidas®IgG) (31,32). Padoan et al also reported a sensitivity of 86.4 (77.0-93.0) for both Mindray®IgM and IgG tests but a new Mindray® generation would give much better performances: 99% and 96% from D1 to D41 for IgG and IgM, respectively (33,34). This new version of Mindray® was not available at the study writing time and merits to be evaluated.…”

SARS-CoV-2 Serology: Utility and Limits of Different Antigen-Based Tests through the Evaluation and the Comparison of Four Commercial Tests

“…Regarding the specificity, Vidas ® IgM and Mindray ® IgM and IgG tests gave positive signals for few pre-pandemic sera (n = 7); such data were also reported by other authors [ 36 , 38 , 39 ]. Cross reactivity with pre-pandemic auto-immune disease patients sera was previously reported [ 41 ].…”

“…Similar low sensitivities for the Vidas ® test were reported by Younes et al (88.3% for Vidas ® IgG after D21) and by Wolf et al (over all sensitivity of 64.9% CI 95% (55.2–73.7) for Vidas ® IgM and 73% CI 95% (63.7–81) for Vidas ® IgG [ 36 , 37 ]. Padoan et al also reported a sensitivity of 86.4 (77.0–93.0) for both Mindray ® IgM and IgG tests but a new Mindray ® generation would give much better performances according to recent literature (99% and 96% from D1 to D41 for IgG and IgM, respectively) [ 38 , 39 ]. This new version of Mindray ® was not available at the study writing time and merits to be evaluated.…”