The WHO has declared the COVID-19 an international health emergency due to the severity of infection progression which become more severe due to its continuous spread globally and the unavailability of appropriate therapy and diagnostics systems . Thus, there is a need for efficient devices to detect SARS-CoV-2 infection at an early stage . Nowadays, the RT-PCR technique is being applied for detecting this virus around the globe; however, factors such as stringent expertise, long diagnostic times, invasive and painful screening, and high costs have restricted the use of RT-PCR methods for rapid diagnostics . Therefore, the development of cost-effective, portable, sensitive, prompt, and selective sensing systems to detect SARS-CoV-2 in biofluids at fM/pM/nM concentrations would be a breakthrough in diagnostics . Immunosensors that show increased specificity and sensitivity are considerably fast, and don ’ t imply costly reagents or instruments, reducing the cost for COVID-19 detection . The current developments in immunosensors perhaps signify the most significant opportunity for a rapid assay to detect COVID-19, without the need of highly skilled professionals and specialized tools to interpret results . Artificial intelligence (AI) and the Internet of Medical Things (IoMT) can also be equipped with this immunosensing approach to investigate useful networking through database management, sharing, and analytics to prevent and manage COVID-19 . Herein, we represent the collective concepts of biomarkers based immunosensors along with AI and IoMT as smart sensing strategies with bioinformatics approach to monitor non-invasive early stage SARS-CoV-2 development, with fast POC diagnostics as the crucial goal . This approach should be implemented quickly and verified practicality for clinical samples before being set in the present times for mass-diagnostic research.