A comparative review of immunoassays for COVID-19 detection

ABSTRACT

Introduction: The gold standard for diagnosis of coronavirus disease 2019 (COVID-19) is detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR), which is expensive, time-consuming and may result in false-negative results. Serological tests can be employed for RT-PCR negative patients, contact tracing, determining the probability of protection against re-infection, and seroepidemiological studies.

Areas covered: The main methodologies of serology-based tests for the detection of SARS-CoV-2 including enzyme-linked immunosorbent assays (ELISAs), chemiluminescent immunoassays (CLIAs) and lateral flow immunoassays (LFIAs) were reviewed and their diagnostic performances were compared. Herein, a literature review on the databases of PubMed, Scopus and Google Scholar between January 1, 2020 and June 30, 2020 based on the main serological methods for COVID-19 detection with the focus on comparative experiments was performed. The review was updated on December 31, 2020.

Expert opinion: Serology testing could be considered as a part of diagnostic panel two-week post symptom onset. Higher sensitivity for serology-based tests could be achieved by determining combined IgG/IgM titers. Furthermore, higher sensitive serological test detecting neutralization antibody could be developed by targeting spike (S) antigen. It was also demonstrated that the sensitivity of ELISA/CLIA-based methods are higher than LFIA devices.

KEYWORDS:

• COVID-19
• SARS-CoV-2
• serology
• ELISA
• CLIA
• LFIA

Article highlights

• It is required to rapidly develop COVID-19 serological assays with high sensitivities for screening and enough specificities to prevent non-essential interventions.

• Due to disagreements between the claimed and real performance of serological diagnostic tests on the market, validation of commercialized serological COVID-19 diagnostic tests across different populations are greatly needed.

• Because of higher IgG and IgM levels in blood in the later stages of the disease, serological tests are more effective in later stages.

• To achieve higher sensitivity, determining combined IgG/IgM titers rather than measuring either antibody type alone is suggested regardless of the examined method.

• Serological test with higher sensitivity, which detects neutralization antibody can be developed by ELISA/CLIA-based methods targeting spike (S) antigen.

Acknowledgments

The figures were drawn using BioRender (https://biorender.com/)

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.