Pandemic preparedness is an important issue in relation to future pandemics. The two studies described here aimed to identify factors predicting the presence and severity of coronavirus disease 2019 (COVID-19) symptoms. The CLOFIT study comprised an online survey among the Dutch population (n = 1415). Perceived immune fitness before the pandemic (2019) and during the first lockdown period (15 March–11 May 2020) and the number and severity of COVID-19 symptoms were assessed. The COTEST study, conducted between December 2020 and June 2021, replicated the CLOFIT study in n = 925 participants who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Dutch commercial test locations. The CLOFIT study revealed that immune fitness before the pandemic was the greatest predictor of the number and severity of COVID-19 symptoms (20.1% and 19.8%, respectively). Other significant predictors included immune fitness during the lockdown (5.5% and 7.1%, respectively), and having underlying diseases (0.4% and 0.5%, respectively). In the COTEST study, for those who tested positive for SARS-CoV-2, immune fitness before the pandemic was the single predictor of the number (27.2%) and severity (33.1%) of COVID-19 symptoms during the pandemic. In conclusion, for those who tested positive for SARS-CoV-2, immune fitness before the pandemic was the strongest predictor of the number and severity of COVID-19 symptoms during the pandemic. Therefore, the development of strategies to maintain an adequate immune fitness must be regarded as an essential component of pandemic preparedness.