High Diagnostic Accuracy of Quantitative SARS-CoV-2 Spike-binding-IgG Assay and Correlation with Viral Neutralizing Activity

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Feb 2

PMID 38304834

Authors

Noriko Iwamoto

Yuki Takamatsu

Yusuke Asai

Kiyoto Tsuchiya

Kouki Matsuda

Yusuke Oshiro

Natsumi Inamura

Mari Terada

Takashi Nemoto

Moto Kimura

Sho Saito

Shinichiro Morioka

Maeda Kenji

Hiroaki Mitsuya

Norio Ohmagari

Affiliations

Soon will be listed here.

Abstract

Background: Antibody testing can easily evaluate the clinical status of patients, aid in the diagnosis of multisystem inflammatory syndrome, and monitor the immunity level in the population. However, the applicability of serological tests in detecting antibodies against the severe acute respiratory syndrome 2 (SARS-CoV-2) spike-binding protein remains limited. This study aimed to quantify both serum-derived neutralizing immunoglobulin-G (IgG) antibody activity and the amount of anti-SARS-CoV-2 Spike-IgG (S-IgG) in convalescent sera/plasmas and evaluate the direct correlation between the IgG-EC values and S-IgG values.

Methods: We evaluated the neutralizing activity of purified IgG (IgG-EC), quantified S-IgG in the serum/plasma of consecutive COVID-19 convalescent individuals using a cell-based virus-neutralizing assay, and determined the correlation between IgG-EC and S-IgG. In addition, we evaluated rational cut-off values using the receiver operating characteristic (ROC) curve and calculated the sensitivity and specificity of the quantitative S-IgG assay for moderate and high IgG-EC.

Results: A high correlation was observed between S-IgG and IgG-EC with a Spearman's ρ value of -0.748 (95 % confidence interval [CI]: -0.804-0.678). Using an IgG-EC of 50 μg/mL and 20 μg/mL as the cut-off values for moderate and high neutralizing activity, respectively, the Youden's index values of 287.5 binding antibody units (BAU)/mL and 454.1 BAU/mL determined from the ROC curve showed the highest diagnostic accuracy, with Kappa values of 0.884 (95 % CI: 0.823-0.946) and 0.920 (95 % CI: 0.681-0.979), respectively.

Conclusions: Quantitative S-IgG tests are a useful and convenient tool for estimating virus-neutralizing activity, with a high correlation with IgG-EC when the rational cut-off value is carefully determined.

References

Okamoto A, Fujigaki H, Iriyama C, Goto N, Yamamoto H, Mihara K . CD19-positive lymphocyte count is critical for acquisition of anti-SARS-CoV-2 IgG after vaccination in B-cell lymphoma. Blood Adv. 2022; 6(11):3230-3233. PMC: 8759802. DOI: 10.1182/bloodadvances.2021006302. View

Addetia A, Crawford K, Dingens A, Zhu H, Roychoudhury P, Huang M . Neutralizing Antibodies Correlate with Protection from SARS-CoV-2 in Humans during a Fishery Vessel Outbreak with a High Attack Rate. J Clin Microbiol. 2020; 58(11). PMC: 7587101. DOI: 10.1128/JCM.02107-20. View

Jack A, Hall A, Maine N, Mendy M, Whittle H . What level of hepatitis B antibody is protective?. J Infect Dis. 1999; 179(2):489-92. DOI: 10.1086/314578. View

Kamegai K, Iwamoto N, Togano T, Maeda K, Takamatsu Y, Miyazato Y . A Fatal Breakthrough COVID-19 Case Following Bendamustine-Rituximab Therapy. Int J Infect Dis. 2022; 121:85-88. PMC: 9054701. DOI: 10.1016/j.ijid.2022.04.058. View

Dolscheid-Pommerich R, Bartok E, Renn M, Kummerer B, Schulte B, Schmithausen R . Correlation between a quantitative anti-SARS-CoV-2 IgG ELISA and neutralization activity. J Med Virol. 2021; 94(1):388-392. PMC: 8426838. DOI: 10.1002/jmv.27287. View

McLean H, Parker Fiebelkorn A, Temte J, Wallace G . Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013; 62(RR-04):1-34. View

Guo L, Ren L, Yang S, Xiao M, Chang D, Yang F . Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clin Infect Dis. 2020; 71(15):778-785. PMC: 7184472. DOI: 10.1093/cid/ciaa310. View

Maeda K, Higashi-Kuwata N, Kinoshita N, Kutsuna S, Tsuchiya K, Hattori S . Neutralization of SARS-CoV-2 with IgG from COVID-19-convalescent plasma. Sci Rep. 2021; 11(1):5563. PMC: 7946899. DOI: 10.1038/s41598-021-84733-5. View

Letizia A, Ge Y, Vangeti S, Goforth C, Weir D, Kuzmina N . SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study. Lancet Respir Med. 2021; 9(7):712-720. PMC: 8049591. DOI: 10.1016/S2213-2600(21)00158-2. View

10.

Yamamoto S, Maeda K, Matsuda K, Tanaka A, Horii K, Okudera K . Coronavirus Disease 2019 (COVID-19) Breakthrough Infection and Post-Vaccination Neutralizing Antibodies Among Healthcare Workers in a Referral Hospital in Tokyo: A Case-Control Matching Study. Clin Infect Dis. 2021; 75(1):e683-e691. PMC: 8755292. DOI: 10.1093/cid/ciab1048. View

11.

Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S . Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N Engl J Med. 2020; 383(24):2320-2332. PMC: 7494251. DOI: 10.1056/NEJMoa2026920. View

12.

Zeng Q, Yang X, Lin B, Li Y, Huang G, Xu Y . Immunological Findings in a Group of Individuals Who Were Poor or Non-Responders to Standard Two-Dose SARS-CoV-2 Vaccines. Vaccines (Basel). 2023; 11(2). PMC: 9963224. DOI: 10.3390/vaccines11020461. View

13.

Hattori S, Higashi-Kuwata N, Hayashi H, Rao Allu S, Raghavaiah J, Bulut H . A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication. Nat Commun. 2021; 12(1):668. PMC: 7843602. DOI: 10.1038/s41467-021-20900-6. View

14.

Harvey R, Rassen J, Kabelac C, Turenne W, Leonard S, Klesh R . Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection. JAMA Intern Med. 2021; 181(5):672-679. PMC: 7905701. DOI: 10.1001/jamainternmed.2021.0366. View

15.

Maeda K, Amano M, Uemura Y, Tsuchiya K, Matsushima T, Noda K . Correlates of neutralizing/SARS-CoV-2-S1-binding antibody response with adverse effects and immune kinetics in BNT162b2-vaccinated individuals. Sci Rep. 2021; 11(1):22848. PMC: 8613264. DOI: 10.1038/s41598-021-01930-y. View

16.

Takamatsu Y, Imai M, Maeda K, Nakajima N, Higashi-Kuwata N, Iwatsuki-Horimoto K . Highly Neutralizing COVID-19 Convalescent Plasmas Potently Block SARS-CoV-2 Replication and Pneumonia in Syrian Hamsters. J Virol. 2021; 96(4):e0155121. PMC: 8865546. DOI: 10.1128/JVI.01551-21. View

17.

Youden W . Index for rating diagnostic tests. Cancer. 1950; 3(1):32-5. DOI: 10.1002/1097-0142(1950)3:1<32::aid-cncr2820030106>3.0.co;2-3. View

18.

Lumley S, ODonnell D, Stoesser N, Matthews P, Howarth A, Hatch S . Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers. N Engl J Med. 2020; 384(6):533-540. PMC: 7781098. DOI: 10.1056/NEJMoa2034545. View

19.

Terada M, Kutsuna S, Togano T, Saito S, Kinoshita N, Shimanishi Y . How we secured a COVID-19 convalescent plasma procurement scheme in Japan. Transfusion. 2021; 61(7):1998-2007. PMC: 8242376. DOI: 10.1111/trf.16541. View

20.

Hall V, Foulkes S, Charlett A, Atti A, Monk E, Simmons R . SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN). Lancet. 2021; 397(10283):1459-1469. PMC: 8040523. DOI: 10.1016/S0140-6736(21)00675-9. View