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Multicenter Study
. 2021 Feb 18;59(3):e02511-20.
doi: 10.1128/JCM.02511-20. Print 2021 Feb 18.

Multicenter Evaluation of the Clinical Performance and the Neutralizing Antibody Activity Prediction Properties of 10 High-Throughput Serological Assays Used in Clinical Laboratories

C Therrien  1 , B Serhir  2 , M Bélanger-Collard  2 , J Skrzypczak  2 , D K Shank  2 , C Renaud  3 , J Girouard  4 , V Loungnarath  4 , M Carrier  5 , G Brochu  6 , F Tourangeau  7 , B Gilfix  8 , A Piche  9 , R Bazin  10 , R Guérin  11 , M Lavoie  11 , V Martel-Laferrière  12   13 , C Fortin  12   13 , A Benoit  14 , D Marcoux  15 , N Gauthier  16 , A M Laumaea  12   13 , R Gasser  12   13 , A Finzi  12   13 , M Roger  2   12   13
Affiliations
Multicenter Study

Multicenter Evaluation of the Clinical Performance and the Neutralizing Antibody Activity Prediction Properties of 10 High-Throughput Serological Assays Used in Clinical Laboratories

C Therrien et al. J Clin Microbiol. .

Abstract

As the coronavirus disease 2019 (COVID-19) pandemic second wave is emerging, it is of the upmost importance to screen the population immunity in order to keep track of infected individuals. Consequently, immunoassays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high specificity and positive predictive values are needed to obtain an accurate epidemiological picture. As more data accumulate about the immune responses and the kinetics of neutralizing-antibody (nAb) production in SARS-CoV-2-infected individuals, new applications are forecast for serological assays such as nAb activity prediction in convalescent-phase plasma from recovered patients. This multicenter study, involving six hospital centers, determined the baseline clinical performances, reproducibility, and nAb level correlations of 10 commercially available immunoassays. In addition, three lateral-flow chromatography assays were evaluated, as these devices can be used in logistically challenged areas. All assays were evaluated using the same patient panels in duplicate, thus enabling accurate comparison of the tests. Seven immunoassays examined in this study were shown to have excellent specificity (98 to 100%) and good to excellent positive predictive values (82 to 100%) when used in a low (5%)-seroprevalence setting. We observed sensitivities as low as 74% and as high as 95% at ≥15 days after symptom onset. The determination of optimized cutoff values through receiver operating characteristic (ROC) curve analyses had a significant impact on the diagnostic resolution of several enzyme immunoassays by increasing the sensitivity significantly without a large trade-off in specificity. We found that spike-based immunoassays seem to be better correlates of nAb activity. Finally, the results reported here will add to the general knowledge of the interlaboratory reproducibility of clinical performance parameters of immunoassays and provide new evidence about nAb activity prediction.

Keywords: COVID-19; SARS-CoV-2; antigen; immunoassays; neutralizing antibodies; serology.

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Figures

FIG 1
FIG 1
Evaluation of the virus neutralization predictive ability of 10 enzyme immunoassays. Spearman correlation analysis of virus neutralization ID50 and immunoassay S/CO values for 67 COVID-19 samples collected between 1 and 43 days after symptom onset. Dotted lines represent the cutoff values for each assay. Data points are presented for two testing sites.
FIG 2
FIG 2
Impact of antigen type on the correlation between antibody binding activity and virus neutralization antibody titers. Spearman r values derived from correlation analysis of ID50 values versus S/CO values for enzyme immunoassays (67 paired data sets from the Se panel). Ag, antigen; N, nucleocapsid; S1, spike domain 1; S1-S2, spike domains 1 and 2; RBD, spike receptor binding domain; S, spike.
FIG 3
FIG 3
Spike-based immunoassays are better predictor of virus neutralization activity. Plotting of Spearman r statistics versus antigen type used by enzyme immunoassays. **, significantly different at a P value of 0.0095; ns, not significant.
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References

    1. Wu F, Zhao S, Yu B, Chen Y-M, Wang W, Song Z-G, Hu Y, Tao Z-W, Tian J-H, Pei Y-Y, Yuan M-L, Zhang Y-L, Dai F-H, Liu Y, Wang Q-M, Zheng J-J, Xu L, Holmes EC, Zhang Y-Z. 2020. A new coronavirus associated with human respiratory disease in China. Nature 579:265–269. doi:10.1038/s41586-020-2008-3. - DOI - PMC - PubMed
    1. Sironi M, Hasnain SE, Rosenthal B, Phan T, Luciani F, Shaw M-A, Sallum MA, Mirhashemi ME, Morand S, González-Candelas F, Editors of Infection, Genetics and Evolution. 2020. SARS-CoV-2 and COVID-19: a genetic, epidemiological, and evolutionary perspective. Infect Genet Evol 84:104384. doi:10.1016/j.meegid.2020.104384. - DOI - PMC - PubMed
    1. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, Si H-R, Zhu Y, Li B, Huang C-L, Chen H-D, Chen J, Luo Y, Guo H, Jiang R-D, Liu M-Q, Chen Y, Shen X-R, Wang X, Zheng X-S, Zhao K, Chen Q-J, Deng F, Liu L-L, Yan B, Zhan F-X, Wang Y-Y, Xiao G-F, Shi Z-L. 2020. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579:270–273. doi:10.1038/s41586-020-2012-7. - DOI - PMC - PubMed
    1. Zhang T, Wu Q, Zhang Z. 2020. Probable pangolin origin of SARS-CoV-2 associated with the COVID-19 outbreak. Curr Biol 30:1346–1351.E2. doi:10.1016/j.cub.2020.03.022. - DOI - PMC - PubMed
    1. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, Bleicker T, Brünink S, Schneider J, Schmidt ML, Mulders DG, Haagmans BL, van der Veer B, van den Brink S, Wijsman L, Goderski G, Romette J-L, Ellis J, Zambon M, Peiris M, Goossens H, Reusken C, Koopmans MP, Drosten C. 2020. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill 25:2000045. doi:10.2807/1560-7917.ES.2020.25.3.2000045. - DOI - PMC - PubMed