| Summary: | COVID-19 continues to spread and has been declared a global emergency. Individuals with current or past infection should be identified as soon as possible to prevent the spread of disease. Surface-enhanced Raman spectroscopy (SERS) is an analytical technique that has the potential to be used to detect viruses at the site of therapy. In this context, SERS is an exciting technique because it provides a fingerprint for any material. It has been used with many COVID-19 virus subtypes, including Deltacron and Omicron, a novel coronavirus. Moreover, flexible SERS substrates, due to their unique advantages of sensitivity and flexibility, have recently attracted growing research interest in real-world applications such as medicine. Reviewing the latest flexible SERS-substrate developments is crucial for the further development of quality detection platforms. This article discusses the ultra-responsive detection methods used by flexible SERS substrate. Multiplex assays that combine ultra-responsive detection methods with their unique biomarkers and/or biomarkers for secondary diseases triggered by the development of infection are critical, according to this study. In addition, we discuss how flexible SERS-substrate-based ultrasensitive detection methods could transform disease diagnosis, control, and surveillance in the future. This study is believed to help researchers design and manufacture flexible SERS substrates with higher performance and lower cost, and ultimately better understand practical applications. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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