BACKGROUND: In the absence of effective pharmaceutical interventions early in an infectious disease outbreak, non-pharmaceutical measures, especially isolating infected individuals, critically limit its impact. The ongoing COVID-19 pandemic has sparked debates on optimal isolation guidelines. This study proposes a variable isolation period approach (variable-period approach), tailoring isolation durations for distinct population groups with varied viral load dynamics. METHODS: To compare our variable-period approach with a fixed-period strategy, we developed a simulation model generating synthetic longitudinal SARS-CoV-2 viral load data. The data was generated from the viral dynamics model parameterized using SARS-CoV-2 Delta patient data in Singapore, accounting for age and vaccination status. RESULTS: Findings show that age and vaccination status significantly influence viral dynamics, with younger age and vaccination linked to shorter viral shedding durations. The variable-period framework suggests longer isolation lengths for older and unvaccinated individuals. By setting the leaking risk (risk of remaining infectious at the end of isolation) below 10%, the optimal fixed-period isolation is 14 days, with an average excess isolation burden of 7.4 unnecessary days. In contrast, the variable-period guideline reduces the excess isolation burden to 6.0 days, with the optimal isolation periods ranging from 9 to 16 days, depending on the population group. We confirmed similar results when we used the effective reproduction number as an alternative to the leaking risk. CONCLUSIONS: In this case, study using the SARS-CoV-2 Delta variant, our analysis demonstrates that unnecessary time spent in isolation can be reduced by adopting variable-period guidelines based on patient characteristics.