Reliability of CMV-IgG kinetics in the diagnosis of CMV primary infection: sensitivity, specificity, and clinical implications

TL;DR

This study shows that relying on CMV-IgG kinetics for diagnosing primary CMV infection during pregnancy is unreliable and can lead to misdiagnosis.

Contribution

The study is the first to demonstrate the unreliability of CMV-IgG kinetics and emphasizes the need for CMV-IgG avidity testing instead.

Findings

CMV-IgG values varied up to 185-fold between different immunoassays for the same sample.

A significant CMV-IgG increase had low sensitivity (32.9%) for predicting recent primary infection.

Retesting IgG 3–5 weeks later is not helpful and can be confusing for diagnosis.

Abstract

Diagnosis of cytomegalovirus (CMV) primary infection (PI) during pregnancy relies on serology (CMV-IgG, IgM, and IgG avidity). However, as for toxoplasmosis, subsequent serology testing 3–5 weeks later is often performed to confirm the diagnosis. In this study, we aimed to show that testing CMV-IgG with different assays may lead to misinterpretation of CMV-IgG kinetics and to determine the sensitivity and specificity of CMV-IgG stability and significant increase to exclude or confirm recent CMV PI. We conducted a retrospective study on (i) a CMV-IgG external quality control program (2015–2022) and (ii) on CMV serology results obtained in our virology laboratory (2013–2023) in pregnant women with positive CMV-IgM and a subsequent serum sample collected 3–5 weeks later. Analysis of 21 CMV-IgG external quality control serum samples highlighted significant differences in CMV-IgG values, with variations up to a factor of 185 between different immunoassays for the same positive sample. In 434 pregnant women, the sensitivity of a significant CMV-IgG increase to predict recent PI was 32.9% (95% CI = 26.5–39.2), while CMV-IgG stability specificity to exclude PI <3 months was 32.9% (95% CI = 26.5–39.2). Our observations highlight the discrepancies in CMV-IgG values with different assays and the major importance of CMV-IgG avidity in the diagnosis of recent CMV PI in case of positive CMV-IgM. We also demonstrate that retesting IgG on a sample collected 3–5 weeks later is not helpful and can be confusing.

This article is the first to address cytomegalovirus (CMV)-IgG kinetics and their reliability in the serological diagnosis of CMV. In our experience, many clinical virologists and laboratory practitioners still rely on kinetics for diagnosis. However, our study clearly demonstrates that this approach is misleading and that avidity testing should always be performed. Additionally, we conducted a robust study highlighting discrepancies between CMV serology techniques, emphasizing the importance for practitioners, particularly gynecologists, to avoid monitoring serology results using different testing methods.

Figures