In absence of extensive testing for SARS-CoV-2, true prevalence of COVID-19 cases at Theni District in India remain unknown. This study examined the prevalence and risk factors of COVID-19 in Theni District, including active cases, discharge, mortality, blood groups, age, and sex-related factors wise COVID-19 positivity rate among patients with severe respiratory illness as reported by Theni medical college and hospital. RTPCR analysis was conducted at Theni Medical College and Hospital in Kanavilakku, Theni District, with 101,201 samples analyzed over the 2020-2022 time period. The highest COVID-19 incidence rates were seen in people aged 60 to 80, irrespective of sex or gender. Males had higher notification rates than females across all age groups.