ABSTRACT
Background/Objectives: Current pandemic situation, together with the continuous emergence of new SARS-CoV-2 variants reveal the need to develop a more versatile tool than PCR-based methods that allows both high throughput COVID-19 diagnostic and specific variant detection at reduced cost and fast turnaround times. Thus, with the aim of overcoming current test limitations and providing a strategy with these characteristics arises our novel next generation sequencing based approach. Method(s): The developed strategy works with RNA samples obtained from nasopharyngeal swabs. RNA samples are processed with our custom laboratory protocol and can be sequenced with any Illumina platform to generate results within a 24h timeframe. A tailored bioinformatic pipeline analyzes the data and generates a clinical-level report. Result(s): Clinical validation results have shown that the designed solution, sensitively and specifically identifies negative and positive samples that display a broad range in viral loads and readily identifies the following major SARS-CoV-2 variants of concern (VoC): Alpha, Beta, Gamma, Delta, Lambda and Omicron (BA.1 and BA.2). Conclusion(s): The versatility of our solution allows the capability of identifying the presence of other common respiratory viruses as well as identifying patients at risk through the identification of susceptibility human variants in the host. This, together with the possibility of easily adding new VoC as they emerge, will make VoC monitoring in entire populations feasible, providing a new perspective on the application of NGS methods in the field of clinical microbiology.