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Abstract Background The COVID-19 pandemic has made devastating impacts on public health and global economy. While most people experience mild symptoms, it is highly transmissible and deadly in at-risk populations. Telemedicine has the potential to prevent hospitalization and provide remote care. Methods This retrospective study included 336 people with COVID-19, among which 141 (42%) and 195 (58%) were in Delta and Omicron dominant groups, respectively. Patients were confirmed to have COVID-19 by PCR or rapid test and were cared for via telemedicine. Severe cases were hospitalized for more intensive treatment. Results The majority of individuals recovered at home (97.02%), while 2.98% required hospitalization. All hospital admissions were in Delta dominant group. No deaths were reported. Delta dominant group was more likely to develop loss of taste and smell, decreased appetite and need longer treatment time than those in Omicron dominant group. Conclusions Telemedicine is a safe measure to provide at-home care for people with COVID-19 infections caused by both Delta and Omicron variants. Trial registration This study was approved by the Institutional Review Board Committee of University of Medicine and Pharmacy at Ho Chi Minh City (IRB No: 22115–DHYD).