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SARS-CoV-2 Serologic Assays in Control and Unknown Populations Demonstrate the Necessity of Virus Neutralization Testing.
J Infect Dis. 2021 04 08; 223(7):1120-1131.JI

Abstract

BACKGROUND

To determine how serologic antibody testing outcome links with virus neutralization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we evaluated individuals for SARS-CoV-2 antibody level and viral neutralization.

METHODS

We compared serum Ig levels across platforms of viral antigens and antibodies with 15 positive and 30 negative SARS-CoV-2 controls followed by viral neutralization assessment. We then applied these platforms to a clinically relevant cohort of 114 individuals with unknown histories of SARS-CoV-2 infection.

RESULTS

In controls, the best-performing virus-specific antibody detection platforms were SARS-CoV-2 receptor binding domain (RBD) IgG (sensitivity 87%, specificity 100%, positive predictive value [PPV] 100%, negative predictive value [NPV] 94%), spike IgG3 (sensitivity 93%, specificity 97%, PPV 93%, NPV 97%), and nucleocapsid protein (NP) IgG (sensitivity 93%, specificity 97%, PPV 93%, NPV 97%). Neutralization of positive and negative control sera showed 100% agreement. Twenty individuals with unknown history had detectable SARS-CoV-2 antibodies with 16 demonstrating virus neutralization. Spike IgG3 provided the highest accuracy for predicting serologically positive individuals with virus neutralization activity (misidentified 1/20 unknowns compared to 2/20 for RBD and NP IgG).

CONCLUSIONS

The coupling of virus neutralization analysis to a spike IgG3 antibody test is optimal to categorize patients for correlates of SARS-CoV-2 immune protection status.

Authors+Show Affiliations

Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington, USA. Department of Pediatric Infectious Disease, Seattle Children's Hospital/University of Washington, Seattle, Washington, USA.Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington, USA.Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington, USA.Department of Statistics, University of Washington, Seattle, Washington, USA.Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington, USA.Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington, USA. Department of Pediatric Infectious Disease, Seattle Children's Hospital/University of Washington, Seattle, Washington, USA.Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington, USA.Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington, USA.Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington, USA.Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington, USA.Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington, USA.

Pub Type(s)

Comparative Study
Journal Article
Observational Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

33367830

Citation

Rathe, Jennifer A., et al. "SARS-CoV-2 Serologic Assays in Control and Unknown Populations Demonstrate the Necessity of Virus Neutralization Testing." The Journal of Infectious Diseases, vol. 223, no. 7, 2021, pp. 1120-1131.
Rathe JA, Hemann EA, Eggenberger J, et al. SARS-CoV-2 Serologic Assays in Control and Unknown Populations Demonstrate the Necessity of Virus Neutralization Testing. J Infect Dis. 2021;223(7):1120-1131.
Rathe, J. A., Hemann, E. A., Eggenberger, J., Li, Z., Knoll, M. L., Stokes, C., Hsiang, T. Y., Netland, J., Takehara, K. K., Pepper, M., & Gale, M. (2021). SARS-CoV-2 Serologic Assays in Control and Unknown Populations Demonstrate the Necessity of Virus Neutralization Testing. The Journal of Infectious Diseases, 223(7), 1120-1131. https://doi.org/10.1093/infdis/jiaa797
Rathe JA, et al. SARS-CoV-2 Serologic Assays in Control and Unknown Populations Demonstrate the Necessity of Virus Neutralization Testing. J Infect Dis. 2021 04 8;223(7):1120-1131. PubMed PMID: 33367830.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2 Serologic Assays in Control and Unknown Populations Demonstrate the Necessity of Virus Neutralization Testing. AU - Rathe,Jennifer A, AU - Hemann,Emily A, AU - Eggenberger,Julie, AU - Li,Zhaoqi, AU - Knoll,Megan L, AU - Stokes,Caleb, AU - Hsiang,Tien-Ying, AU - Netland,Jason, AU - Takehara,Kennidy K, AU - Pepper,Marion, AU - Gale,Michael,Jr PY - 2020/09/30/received PY - 2020/12/23/accepted PY - 2020/12/29/pubmed PY - 2021/4/21/medline PY - 2020/12/28/entrez KW - SARS-CoV-2 KW - antibody KW - immunity KW - neutralization KW - serologic KW - two-tiered testing SP - 1120 EP - 1131 JF - The Journal of infectious diseases JO - J Infect Dis VL - 223 IS - 7 N2 - BACKGROUND: To determine how serologic antibody testing outcome links with virus neutralization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we evaluated individuals for SARS-CoV-2 antibody level and viral neutralization. METHODS: We compared serum Ig levels across platforms of viral antigens and antibodies with 15 positive and 30 negative SARS-CoV-2 controls followed by viral neutralization assessment. We then applied these platforms to a clinically relevant cohort of 114 individuals with unknown histories of SARS-CoV-2 infection. RESULTS: In controls, the best-performing virus-specific antibody detection platforms were SARS-CoV-2 receptor binding domain (RBD) IgG (sensitivity 87%, specificity 100%, positive predictive value [PPV] 100%, negative predictive value [NPV] 94%), spike IgG3 (sensitivity 93%, specificity 97%, PPV 93%, NPV 97%), and nucleocapsid protein (NP) IgG (sensitivity 93%, specificity 97%, PPV 93%, NPV 97%). Neutralization of positive and negative control sera showed 100% agreement. Twenty individuals with unknown history had detectable SARS-CoV-2 antibodies with 16 demonstrating virus neutralization. Spike IgG3 provided the highest accuracy for predicting serologically positive individuals with virus neutralization activity (misidentified 1/20 unknowns compared to 2/20 for RBD and NP IgG). CONCLUSIONS: The coupling of virus neutralization analysis to a spike IgG3 antibody test is optimal to categorize patients for correlates of SARS-CoV-2 immune protection status. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/33367830/SARS_CoV_2_Serologic_Assays_in_Control_and_Unknown_Populations_Demonstrate_the_Necessity_of_Virus_Neutralization_Testing_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jiaa797 DB - PRIME DP - Unbound Medicine ER -