Variation in LOD Across SARS-CoV-2 Assay Systems: Need for Standardization

Abstract

Multiple SARS-CoV-2 emergency use authorization (EUA) tests are being used for clinical testing across various clinical testing laboratories for meeting the diagnostic challenges of the ongoing pandemic. However, cross-assay variations in performance characteristics need to be recognized. A better understanding is needed of the clinical implications of cross-assay variation in performance characteristics, particularly in the limit of detection (LOD) of the SARS-CoV-2 assays used for clinical testing. Herein, a snapshot of the diversity of SARS-CoV-2 EUA analytical assay systems including methodologies, assay designs, and technology platforms is presented. Factors affecting the variations in LOD are discussed. Potential measures that may standardize across the various assay systems are suggested. Development of international standards and reference materials for the establishment of performance characteristics may substantially alleviate potential clinical decision-making challenges. Finally, cross-assay variation in LODs among the diverse SARS-CoV-2 diagnostic assays impacts clinical decision-making with multiple assay systems in use and lack of standardization across platforms. International standards in parallel with continued cross-platform studies and collaborative efforts across pertinent healthcare entities will help mitigate some of the clinical decision-making challenges.