Comparative Analysis of High-Performance Bioanalytical Methods for SARS-CoV-2 Serodiagnosis

The SARS-CoV-2 pandemic was declared a global health emergency by the World Health Organization in March 2020 and represented one of the most significant biomedical challenges of the 21st century. The unprecedent scale of viral transmission, clinical heterogeneity, and global impact on healthcare systems underscored the urgent need for rapid, sensitive, and reliable diagnostic tools. In addition to molecular testing, which played a central role in the identification of active infections, serological assays became essential for assessing the magnitude, duration, and quality of immune responses following both natural infection and vaccination. This study presents a comparative analysis of three high-performance serological platforms: Enzyme-Linked Immunosorbent Assay (ELISA), Luminex, and Meso Scale Discovery (MSD). —The aim was to quantify specific antibodies against the major SARS-CoV-2 antigens, corresponding to the full-length Spike protein (S), the receptorbinding domain (RBD), and the Nucleocapsid (N) protein. Fifty human serum samples from PCR-confirmed SARS-CoV-2-positive donors were analyzed to evaluate each platform’s analytical performance, including sensitivity, reproducibility, dynamic range, and multiplexing capability. Correlation analyses demonstrated a high degree of concordance among the three systems, with correlation coefficients exceeding 0.9 for S and RBD antigens, confirming the strong reliability and inter-assay agreement of quantitative antibody detection. Furthermore, integrating IgG avidity assessment within the multiplex framework provided qualitative insight into antibody maturation, revealing that vaccination or booster doses induce antibodies with higher avidity and enhance neutralizing potential compared to those generated by natural infection. The results confirm that multiplex immunoassays such as Luminex and MSD offer superior analytical power, efficiency, and data richness compared to conventional ELISA, enabling comprehensive seroprofiling from minimal sample volumes. These technologies represent a valuable asset for immunological surveillance and vaccine monitoring, paving the way for an integrated and high-resolution approach to immunodiagnostics and global health preparedness.