Technical considerations to development of serological tests for SARS-CoV-2

Area of Science:

• Clinical diagnostics
• Immunology
• Public health

Background:

• The COVID-19 pandemic highlighted the need for accurate serological testing for diagnosis and exposure assessment.
• Over 90 companies rapidly deployed SARS-CoV-2 assays, many with unsubstantiated claims regarding accuracy and regulatory status.
• The U.S. Food and Drug Administration implemented an Emergency Use Authorization (EUA) to expedite assay availability, bypassing standard approval processes.

Purpose of the Study:

• To evaluate the role of serological testing in understanding SARS-CoV-2 exposure and immunity.
• To discuss the challenges in developing and validating serological assays during the pandemic.
• To emphasize technical challenges in SARS-CoV-2 serology development, particularly for lateral flow assay technology.

Main Methods:

• Review of serological assay platforms, including lateral flow assays, ELISAs, and chemiluminescence.
• Analysis of the regulatory landscape, including the Emergency Use Authorization (EUA) process.
• Discussion of practical challenges faced by manufacturers and end-users in assay development, deployment, and interpretation.

Main Results:

• Many initial serological assays exhibited quality issues, leading to their withdrawal from the market.
• Lateral flow assays offer advantages in cost, speed, and accessibility.
• Established laboratory platforms provide throughput and quantification but present development and interpretation challenges.

Conclusions:

• Despite technical simplicity, SARS-CoV-2 serology assays face significant practical challenges.
• Vetting and validation are critical for ensuring the reliability of diagnostic and exposure assessment tools.
• Further research and development are needed to optimize serological testing for infectious diseases.