Serological testing for SARS-CoV-2 antibodies in clinical practice: A comparative diagnostic accuracy study

Area of Science:

• Infectious Diseases
• Immunology
• Diagnostic Accuracy

Background:

• Serological tests are crucial for monitoring infectious diseases and assessing host immunity.
• Manufacturer-provided diagnostic accuracy data for these tests may stem from biased studies, leaving real-world clinical performance unclear.

Purpose of the Study:

• To evaluate the diagnostic accuracy of various serological testing strategies for identifying previous coronavirus disease-2019 (COVID-19).
• To assess the ability of these tests to predict neutralizing antibodies against SARS-CoV-2 in clinical practice.

Main Methods:

• Prospective study of 2573 healthcare workers and 1085 inpatients with suspected COVID-19.
• Utilized various immunoassays (ELISA, CLIA, ECLIA, LFI) targeting different SARS-CoV-2 epitopes (N, RBD, S1/S2) and antibody subtypes (IgG, pan-Ig).
• Defined previous COVID-19 by positive real-time PCR; neutralization assays performed on a subgroup.

Main Results:

• High sensitivity (≥85%) for detecting previous COVID-19 was observed with anti-N ECLIA (86.8%) and anti-S1 ELISA (86.2%).
• Sensitivity for detecting neutralizing antibodies was high (≥85%) with anti-S1 ELISA (92.7%), anti-N ECLIA (91.7%), and others.
• Specificity for both detection of previous infection and neutralizing antibodies was generally high across multiple assays, with some exceptions.

Conclusions:

• The diagnostic accuracy of serological tests for SARS-CoV-2 antibodies varies significantly in clinical practice.
• Observed sensitivities for detecting previous COVID-19 often deviated from manufacturer specifications.
• These findings are critical for accurate population infection burden estimation and assessing protection against re-infection.