What are the types of coronavirus disease 2019 (COVID-19) antibody detection tests?

Updated: Apr 02, 2021
  • Author: James J Dunn, PhD, D(ABMM), MT(ASCP); more...
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Two SARS-CoV-2 antigens have been used as antigenic targets for the development of antibody detection assays: spike (S) and nucleocapsid (N) proteins. S protein binds to the cell surface angiotensin-converting enzyme 2 (ACE2) receptor, whereas the N protein plays crucial roles in viral replication and assembly, is highly conserved, and induces antibodies sooner than S protein during infection. [64] However, studies suggest that a host’s neutralizing antibodies are predominantly those directed against the S protein. [65] .

Available immunoassays are capable of detecting all isotypes of antibodies: IgA, IgM, and IgG. Total antibody detection assays are designed to determine levels of all isotypes combined. All currently authorized tests provide either qualitative or semi-quantitative results.

Commercial SARS-CoV-2 serologic assays include the following:

  • Automated direct chemiluminescence immunoassay (CIA)
  • Enzyme-linked immunosorbent assay (ELISA)
  • Rapid lateral-flow assay (LFA)
  • Bioassays such as those employing plaque reduction and microneutralization

Automated direct chemiluminescence immunoassay

In CIA, quantification is provided by luminescence detection, with this method using a combination of recombinant antigens coated onto magnetic beads. Data show that the CIA technique for detection of SARS-CoV-2 antibodies offers excellent sensitivity and specificity for determination of the presence of total antibodies or selected isotypes. It also provides an automation option, allowing high-throughput sample testing. [66]

Enzyme-linked immunosorbent assay

ELISA can detect total antibody content or IgA, IgM, or IgG selectively. ELISAs are often utilized to study the timeline/seroconversion of antibody production in patients. The basis of the ELISA format is antibody-antigen reactivity; the analyte in a patient sample is detected using an enzyme conjugate that converts specific substrate into a measurable signal that is used as a readout. The advantages of ELISA include high-throughput patient testing. Disadvantages include limited reproducibility due to lack of standardization, variable detection limits, and use of variable antigens. Therefore, sensitivity and specificity vary widely across assays and even within assays validated by different users. [66]

Rapid lateral-flow assay,

LFA, similar to ELISA, employs SARS-CoV-2 antigen as a capture agent, but in a lateral-flow strip format. [67] The most appealing advantages of the lateral-flow format are fast turnaround time (10-30 minutes) when compared with classic ELISA (several hours), along with minimal sample processing. Most LFAs provide qualitative, visual results that are subjectively interpreted by the operator, enabling near-patient testing in low-resource settings. However, the current cost of LFA is higher than that of high-throughput ELISA. Moreover, although LFA has the potential to expand COVID-19 diagnostic capacity, these tests are still being evaluated, and a large study found alarming inconsistencies among 10 commercially available LFAs. [68] Therefore, LFA results should be interpreted with caution, and follow-up testing is recommended.


Bioassays such as those employing plaque reduction and microneutralization provide essential data for the validation of candidate diagnostic tests. However, they require specialized expertise and are offered by a limited number of highly specialized laboratories.

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