SARS-CoV-2 Serologic Assays in Control and Unknown Populations Demonstrate the Necessity of Virus Neutralization Testing. (25th December 2020)

• Record Type: Journal Article
• Authors: Rathe, Jennifer A; Hemann, Emily A; Eggenberger, Julie; Li, Zhaoqi; Knoll, Megan L; Stokes, Caleb; Hsiang, Tien-Ying; Netland, Jason; Takehara, Kennidy K; Pepper, Marion; Gale, Michael
• Is Part Of: Journal of infectious diseases. Volume 223:Number 7(2021)
• Page Start: 1120
• Page End: 1131
• Publication Date: 2020-12-25
• Subjects: SARS-CoV-2 -- serologic -- immunity -- two-tiered testing -- neutralization -- antibody; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiaa797
• Languages: English
• ISSNs: 0022-1899

Abstract

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. Abstract : This study determined that spike IgG3 serologic testing best predicted virus neutralization of SARS-CoV-2. Further, 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.