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Updated: Nov 25, 2025

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Immunologic Testing for SARS-CoV-2 Infection from the Antigen Perspective.

Dandan Li1,2, Jinming Li3,2,4

  • 1National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Journal of Clinical Microbiology
|December 15, 2020
PubMed
Summary

Identifying optimal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens is crucial for accurate COVID-19 serological tests. The S1 domain of the spike protein shows high specificity, while antigen combinations improve diagnostic performance.

Keywords:
COVID-19SARS-CoV-2antigencross-reactionserology testing

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Area of Science:

  • Immunology
  • Virology
  • Diagnostic Development

Background:

  • The COVID-19 pandemic, caused by SARS-CoV-2, necessitates reliable diagnostic tools.
  • Serological tests detect antibody responses to SARS-CoV-2 infection.
  • Understanding antigen suitability for serological testing is critical for accuracy and specificity.

Purpose of the Study:

  • To evaluate the suitability of different SARS-CoV-2 antigens for serological testing.
  • To determine which antigens offer the highest sensitivity and specificity.
  • To assess cross-reactivity of antigens with other coronaviruses.

Main Methods:

  • Review of previous studies on SARS-CoV-2 antigen performance in serological assays.
  • Analysis of antigen specificity and sensitivity data, including cross-reactivity.
  • Exploration of multi-antigen protein arrays for enhanced diagnostic performance.

Main Results:

  • The S1 domain of the spike protein exhibits low cross-reactivity with other coronaviruses, indicating high specificity.
  • The receptor-binding domain (RBD) shows higher sensitivity than the nucleocapsid (N) protein.
  • Combinations of antigens in protein arrays improve diagnostic performance compared to single antigens.

Conclusions:

  • The S1 domain is a highly specific antigen for SARS-CoV-2 serological testing.
  • Antigen combinations offer improved sensitivity and specificity for COVID-19 diagnostics.
  • Further development of sensitive and specific diagnostic methods is essential for accurate SARS-CoV-2 detection.