Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) represent a significant global health burden, with an estimated seroprevalence of 67 % for HSV-1 among individuals under 50 years and 13 % for HSV-2 among those aged 15–49 as of 2016 [1]. HSV-associated diseases are primarily diagnosed based on clinical presentation, supported by molecular methods such as polymerase chain reaction (PCR) for active infections. However, PCR has limitations in detecting latent or subclinical infections, where type-specific serological testing for immunoglobulin G (IgG) antibodies targeting HSV-1 and HSV-2 provides valuable diagnostic and epidemiological insights [2], [3], [4], [5]. Current recommendations emphasize their selective use in patients with recurrent or atypical genital disease when direct detection methods are inconclusive, in first-episode genital herpes to differentiate primary from established infection, and in sexual partners of individuals with known HSV infection for counseling on transmission risk [6].

Efficient, sensitive, and specific serological diagnostics are needed for both clinical care and potential screening to detect the vast majority of HSV infections that currently remain undiagnosed [7], [8], [9], [10], [11], [12], [13]. Type-specific IgG antibodies typically become detectable between two weeks and three months after symptom onset and persist lifelong. Although type-specific HSV serological assays are increasingly available, their performances vary across platforms [12].

False-negative results during early infection often require repeated tests in ambiguous cases, while suboptimal specificity leading to false positives results especially at low index values (< 3.0), can cause unnecessary psychological distress, stigma, and inappropriate clinical interventions or counseling. As a result, their role in clinical guidelines remains limited [14], [15], [16], [17], [18], [19], [20]. That’s why the Centers for Disease Control and Prevention (CDC) Sexually Transmitted Infection (STI) Treatment Guidelines recommend a two-step testing process, using a sensitive enzyme/chemiluminescence assay for screening followed by a second, more specific confirmatory assay by western blot (WB) [21], [22].

Furthermore, the clinical relevance of 'high antibody levels' remains unclear. Some studies showed that high antibody levels before transplantation increase the risk of herpetic lesions and viral shedding, highlighting the importance of HSV serological evaluation [23], [24]. The absence of standardization, coupled with elevated index values that do not consistently correlate with post-transplant outcomes, creates significant ambiguity. This uncertainty underscores the need for further research to clarify whether these values indicate an increased risk of reactivation or have other clinical implications.

To conclude, the clinical utility of HSV serology remains debated due to evolving diagnostic technologies, different clinical guidelines, and persistent controversies regarding its use and limitations [6], [21], [25], [26], [27], [28].

This issue is particularly concerning for asymptomatic individuals, including pregnant women, where routine screening is not recommended by the U.S. Preventive Services Task Force (USPSTF) due to the potential harms outweighing the benefits [6] and by the European guidelines which recommend HSV screening only in specific clinical scenarios [26].

The same controversy appears in the context of transplantation because severe HSV disease can occur in HSV-seropositive before transplantation. Many centers, however, do evaluate recipient HSV serology or administer universal prophylaxis for the first 1–3 months after transplantation, predominantly to prevent HSV reactivation, which occurs in 35–68 % of HSV-seropositive recipients not receiving antiviral prophylaxis. Therefore, American Society of Transplantation (AST) does not recommend routine pre-transplant HSV screening, as prophylactic antiviral therapy is commonly administered regardless of serostatus [27], [28]. However, some studies emphasized that recipient HSV IgG serostatus should be determined prior to transplantation for appropriate post-transplant risk stratification [29], [30], [31], [32].

In this context, this study aims to assess the analytical performance of the newly developed Abbott Alinity-i HSV-1 and HSV-2 IgG chemiluminescent immunoassays (CLIAs) for the detection of type-specific IgG antibodies, comparing to them with widely used platforms such as the DiaSorin Liaison HSV-1/2 IgG CLIA and the Bio-Rad BioPlex HSV-1/2 IgG multiplex bead assay.