Next-Generation Nucleic Acid-Based Diagnostics for Viral Pathogens: Lessons Learned from the SARS-CoV-2 Pandemic.

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), catalyzed unprecedented innovation in molecular diagnostics to address critical gaps in rapid pathogen detection. Over the past five years, CRISPR-based systems, isothermal amplification techniques, and portable biosensors have emerged as transformative tools for nucleic acid detection, offering improvements in speed, sensitivity, and point-of-care applicability compared to conventional PCR. While numerous reviews have cataloged the technical specifications of these platforms, a critical gap remains in understanding the strategic and economic hurdles to their real-world implementation. This review provides a forward-looking analysis of the feasibility, scalability, and economic benefits of integrating these next-generation technologies into future pandemic-response pipelines. We synthesize advances in coronavirus-specific diagnostic platforms and attempt to highlight the need for their implementation as a cost-saving measure during surges in clinical demand. We evaluate the feasibility of translating these technologies-particularly CRISPR-Cas integration with recombinase polymerase amplification (RPA)-into robust first-line diagnostic pipelines for novel viral threats. By analyzing the evolution of diagnostic strategies during the COVID-19 era, we aim to provide strategic insights and new directions for developing and deploying effective detection platforms to better confront future viral pandemics.