Performance of Three Anti-SARS-CoV-2 Anti-S and One Anti-N Immunoassays for the Monitoring of Immune Status and Vaccine Response

Y Victoria Zhang; Attila Kumanovics; Joesph Wiencek; Stacy E F Melanson; Tanzy Love; Alan H B Wu; Zhen Zhao; Qing H Meng; David D Koch; Fred S Apple; Caitlin R Ondracek; Robert H Christenson

doi:10.3390/v16020292

Performance of Three Anti-SARS-CoV-2 Anti-S and One Anti-N Immunoassays for the Monitoring of Immune Status and Vaccine Response

Viruses. 2024 Feb 14;16(2):292. doi: 10.3390/v16020292.

Authors

Y Victoria Zhang¹, Attila Kumanovics², Joesph Wiencek³, Stacy E F Melanson^{4

5}, Tanzy Love⁶, Alan H B Wu⁷, Zhen Zhao⁸, Qing H Meng⁹, David D Koch¹⁰, Fred S Apple^{11

12}, Caitlin R Ondracek¹³, Robert H Christenson¹⁴

Affiliations

¹ Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
² Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
³ Department of Pathology, Microbiology and Immunology, Vanderbilt School of Medicine, Nashville, TN 37240, USA.
⁴ Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
⁵ Harvard Medical School, Boston, MA 02115, USA.
⁶ Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY 14642, USA.
⁷ Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA.
⁸ Department of Laboratory Medicine and Pathology, Weill Cornell Medicine, New York, NY 10065, USA.
⁹ Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁰ Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30303, USA.
¹¹ Department of Laboratory Medicine and Pathology, Hennepin Healthcare/Hennepin County Medical Center, Minneapolis, MN 55404, USA.
¹² Hennepin Healthcare Research Institute, Minneapolis, MN 55404, USA.
¹³ Association for Diagnostics & Laboratory Medicine, Washington, DC 22203, USA.
¹⁴ Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Abstract

This study aimed to evaluate and compare the performance of three anti-S and one anti-N assays that were available to the project in detecting antibody levels after three commonly used SARS-CoV-2 vaccines (Pfizer, Moderna, and Johnson & Johnson). It also aimed to assess the association of age, sex, race, ethnicity, vaccine timing, and vaccine side effects on antibody levels in a cohort of 827 individuals. In September 2021, 698 vaccinated individuals donated blood samples as part of the Association for Diagnostics & Laboratory Medicine (ADLM) COVID-19 Immunity Study. These individuals also participated in a comprehensive survey covering demographic information, vaccination status, and associated side effects. Additionally, 305 age- and gender-matched samples were obtained from the ADLM 2015 sample bank as pre-COVID-19-negative samples. All these samples underwent antibody level analysis using three anti-S assays, namely Beckman Access SARS-CoV-2 IgG (Beckman assay), Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG (Ortho assay), Siemens ADVIA Centaur SARS-CoV-2 IgG (Siemens assay), and one anti-N antibody assay: Bio-Rad Platelia SARS-CoV-2 Total Ab assay (BioRad assay). A total of 827 samples (580 COVID-19 samples and 247 pre-COVID-19 samples) received results for all four assays and underwent further analysis. Beckman, Ortho, and Siemens anti-S assays showed an overall sensitivity of 99.5%, 97.6%, and 96.9%, and specificity of 90%, 100%, and 99.6%, respectively. All three assays indicated 100% sensitivity for individuals who received the Moderna vaccine and boosters, and over 99% sensitivity for the Pfizer vaccine. Sensitivities varied from 70.4% (Siemens), 81.5% (Ortho), and 96.3% (Beckman) for individuals who received the Johnson & Johnson vaccine. BioRad anti-N assays demonstrated 46.2% sensitivity and 99.25% specificity based on results from individuals with self-reported infection. The highest median anti-S antibody levels were measured in individuals who received the Moderna vaccine, followed by Pfizer and then Johnson & Johnson vaccines. Higher anti-S antibody levels were significantly associated with younger age and closer proximity to the last vaccine dose but were not associated with gender, race, or ethnicity. Participants with higher anti-S levels experienced significantly more side effects as well as more severe side effects (e.g., muscle pain, chills, fever, and moderate limitations) (p < 0.05). Anti-N antibody levels only indicated a significant correlation with headache. This study indicated performance variations among different anti-S assays, both among themselves and when analyzing individuals with different SARS-CoV-2 vaccines. Caution should be exercised when conducting large-scale studies to ensure that the same platform and/or assays are used for the most effective interpretation of the data.

Keywords: COVID-19; SARS-CoV-2; anti-N antibody; anti-S antibody; vaccine.

MeSH terms

Antibodies, Viral
COVID-19 Vaccines
COVID-19* / diagnosis
COVID-19* / prevention & control
Humans
Immunoassay
Immunoglobulin G
SARS-CoV-2
Vaccines*

Substances

COVID-19 Vaccines
Vaccines
Antibodies, Viral
Immunoglobulin G

Grants and funding

This study was supported by the Association for Diagnostics & Laboratory Medicine (formerly the American Association for Clinical Chemistry) as the COVID-19 Immunity Study and its corporate sponsors.