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Owning to the outbreak of COVID-19, individuals have to spend more time indoor. It is therefore essential to prepare for a long-term healthy indoor working environment in the transition of post COVID-19 pandemic. However, there is no relevant research so far in investigating such crisis impacts around indoor environmental quality and economic-health issues while home offices are expected becoming common practice soon. Therefore, a case of single-family house in Sweden is specially investigated using IDA ICE. By comparing four predominant ventilation approaches, three operational schedules are proposed, covering different confinement for occupants. Main results show that the demand response ventilation (DRV) generally should sacrifice in remarkable performance in energy saving, and emission reduction to better confront with more challenges in indoor air quality, occupied thermal dissatisfaction fraction and air stagnation under the challenge of COVID-19 pandemic scenario. Altered ventilation strategy should be customized from increased outdoor air supply, various demand-control signal, displacement method towards a heathier homeworking environment. © International Building Performance Simulation Association, 2022