Comprehensive, Comparative Evaluation of 35 Manual SARS-CoV-2 Serological Assays

Area of Science:

• Infectious Diseases
• Diagnostic Technologies
• Public Health

Background:

• The COVID-19 pandemic led to a rapid influx of diagnostic devices, often with limited performance evaluation.
• Regulatory bodies permitted emergency use, bypassing comprehensive assessments for many SARS-CoV-2 assays.
• The World Health Organization (WHO) established Target Product Profiles (TPPs) for acceptable SARS-CoV-2 assay performance.

Purpose of the Study:

• To comparatively evaluate the performance of 35 anti-SARS-CoV-2 diagnostic tests against WHO TPPs.
• To assess the suitability of rapid diagnostic tests and enzyme immunoassays (EIAs) for use in low- and middle-income countries (LMICs).
• To determine the accuracy, specificity, and cross-reactivity of available serology tests.

Main Methods:

• Evaluated 26 rapid diagnostic tests and 9 EIAs for anti-SARS-CoV-2 antibodies.
• Assessed test kits against WHO TPPs and other performance characteristics, including sensitivity and specificity.
• Tested kits with samples potentially containing cross-reacting or interfering substances, and samples positive for other coronaviruses.

Main Results:

• Sensitivity ranged from 60.1% to 100%; specificity ranged from 56.0% to 100%.
• Only a few of the 35 evaluated test kits met the WHO TPP performance requirements.
• Significant heterogeneity in performance was observed, with many tests showing false reactivity with cross-reacting or interfering substances.

Conclusions:

• Comprehensive performance evaluation of diagnostic kits is crucial, especially during pandemics.
• Independent comparative assessments are vital for selecting reliable SARS-CoV-2 tests for diagnostics and surveillance.
• The significant variability in test performance underscores the need for stringent quality control and validation before procurement and use.