Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2021 Mar;40(3):485-494.
doi: 10.1007/s10096-020-04128-8. Epub 2021 Jan 6.

Inference of SARS-CoV-2 spike-binding neutralizing antibody titers in sera from hospitalized COVID-19 patients by using commercial enzyme and chemiluminescent immunoassays

Arantxa Valdivia  1 , Ignacio Torres  1 , Víctor Latorre  2 , Clara Francés-Gómez  2 , Eliseo Albert  1 , Roberto Gozalbo-Rovira  3 , María Jesús Alcaraz  1 , Javier Buesa  1   3 , Jesús Rodríguez-Díaz  3 , Ron Geller  2 , David Navarro  4   5
Affiliations
Comparative Study

Inference of SARS-CoV-2 spike-binding neutralizing antibody titers in sera from hospitalized COVID-19 patients by using commercial enzyme and chemiluminescent immunoassays

Arantxa Valdivia et al. Eur J Clin Microbiol Infect Dis. 2021 Mar.

Abstract

Whether antibody levels measured by commercially available enzyme or chemiluminescent immunoassays targeting the SARS-CoV-2 spike (S) protein can act as a proxy for serum neutralizing activity remains to be established for many of these assays. We evaluated the degree of correlation between neutralizing antibodies (NtAb) binding the SARS-CoV-2 spike (S) protein and SARS-CoV-2-S-IgG levels measured by four commercial immunoassays in sera drawn from hospitalized COVID-19 patients. Ninety sera from 51 hospitalized COVID-19 patients were tested by a pseudotyped virus neutralization assay, the LIAISON SARS-CoV-2 S1/S2 IgG, the Euroimmun SARS-CoV-2 IgG ELISA, the MAGLUMI 2019-nCoV IgG, and the COVID-19 ELISA IgG assays. Overall, the results obtained with the COVID-19 ELISA IgG test showed the highest agreement with the NtAb assay (κ, 0.85; 95% CI, 0.63-1). The most sensitive tests were the pseudotyped virus NtAb assay and the COVID-19 ELISA IgG assay (92.2% for both). Overall, the degree correlation between antibody titers resulting in 50% virus neutralization (NtAb50) in the pseudotyped virus assay and SARS-CoV-2 IgG levels was strong for the Euroimmun SARS-CoV-2 IgG ELISA (rho = 0.73) and moderate for the remaining assays (rho = 0.48 to 0.59). The kinetic profile of serum NtAb50 titers could not be reliably predicted by any of the SARS-CoV-2 IgG immunoassays. The suitability of SARS-CoV-2-S-IgG commercial immunoassays for inferring neutralizing activity of sera from hospitalized COVID-19 patients varies widely across tests and is influenced by the time of sera collection after the onset of symptoms.

Keywords: COVID-19; Chemiluminescent immunoassays; Enzyme-linked immunosorbent assay; Neutralizing antibodies; SARS-CoV-2.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Correlation between NtAb50 titers measured by a SARS-CoV-2-S pseudotyped virus neutralization assay and IgG levels measured by commercial SARS-CoV-2 IgG immunoassays in all sera (a), in sera obtained within the first two weeks after the onset of symptoms (<15 days; b), and in sera collected afterward (≥ 15 days; c). For (a), Rho and P values were as follows: Euroimmun SARS-CoV-2 IgG , 0.73 and P<0.001; MAGLUMI 2019-nCoV IgG, 0.48 and P<0.001; LIAISON SARS-CoV-2 S1/S2 IgG, 0.52 and P<0.001. COVID-19 ELISA IgG, 054 and P<0.001. For (b) Rho and P values were as follows: 0.80 and P<0.001; 0.54 and P<0.001; 0.68 and P<0.001; 0.63 and P<0.001, respectively. For (c) Rho and P values were as follows: 0.55 and P<0.001; 0.30 and P<0.03; 0.32 and P=0.02; 0.39 and P=0.005, respectively
Fig. 2
Fig. 2
ROC curve analysis for establishing the optimal SARS-CoV-2 IgG threshold levels that predict the presence of high NtAb50 titers (≥ 1/160) in hospitalized patients with COVID-19 for the Euroimmun SARS-CoV-2 IgG ELISA (a), LIAISON SARS-CoV-2 S1/S2 IgG assay (b), MAGLUMI 2019-nCoV IgG (c), and COVID-19 ELISA IgG (d) assays
Fig. 3
Fig. 3
Kinetics patterns of serum NtAb50 titers quantitated by a SARS-CoV-2-S pseudotyped virus neutralization assay and SARS-CoV-2 IgG levels measured by commercial immunoassays in two representative patients displaying concordant (upper panels) or discordant (lower panels) kinetics
See this image and copyright information in PMC

References

    1. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062. doi: 10.1016/S0140-6736(20)30566-3. - DOI - PMC - PubMed
    1. Guan W-J, Ni Z-Y, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS. Clinical characteristics of coronavirus disease 2019 in China. New Engl J Med. 2020;382:1708–1720. doi: 10.1056/NEJMoa2002032. - DOI - PMC - PubMed
    1. Moore JP, Klasse PJ (2020) SARS-CoV-2 vaccines: ‘Warp Speed’ needs mind melds not warped minds. J Virol. 10.1128/JVI.01083-20 - PMC - PubMed
    1. Zohar T, Alter G. Dissecting antibody-mediated protection against SARS-CoV-2. Nat Rev Immunol. 2020;20:392–394. doi: 10.1038/s41577-020-0359-5. - DOI - PMC - PubMed
    1. Zost SJ, Gilchuk P, Case JB, Binshtein E, Chen RE, Nkolola JP, Schäfer A, Reidy JX, Trivette A, Nargi RS, Sutton RE, Suryadevara N, Martinez DR, Williamson LE, Chen EC, Jones T, Day S, Myers L, Hassan AO, Kafai NM, Winkler ES, Fox JM, Shrihari S, Mueller BK, Meiler J, Chandrashekar A, Mercado NB, Steinhardt JJ, Ren K, Loo YM, Kallewaard NL, McCune BT, Keeler SP, Holtzman MJ, Barouch DH, Gralinski LE, Baric RS, Thackray LB, Diamond MS, Carnahan RH, Crowe JE Jr (2020) Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature. 10.1038/s41586-020-2548-6 - PMC - PubMed