peer reviewed ; Background and objectives As the influence of stress syndromes on the evolution of Parkinson’s disease (PD) remains largely unexplored, the COVID-19 pandemic offers the opportunity to evaluate the stress impact of the COVID-19 pandemic on PD trajectories. Methods This longitudinal observational case-control study used data from the Luxembourg Parkinson’s Study (1). A pandemic PD group with exposure to the restrictions imposed by the COVID-19 pandemic but without COVID-19 infection (n=79) was compared to a prepandemic PD control group (n= 117) that has never been exposed to any pandemic restrictions. All patients underwent three annual visits. The last analyzed in-person visit of the pandemic group occurred during the early pandemic phase, between September 2020 and March 2021. Motor and cognitive status were established through standardized in-person exams. Patients of the PD pandemic group selfrated their resilience and risk for posttraumatic stress disorder (PTSD) and, at visit 2 and 3, underwent the Olink panel of 92 serological inflammation markers. The primary outcome was motor PD progression as rated by the MDS-UPDRS part III score. The secondary outcomes were other progression scores (MDS-UPDRS I and II), cognitive performance (Montreal Cognitive Assessment), symptoms of depression (Beck Depression Inventory), risk for PTSD (revised Impact of Event Scale) and resilience (Brief Resilience Scale). Measures tested for statistical associations with these outcomes include demographic, lifestyle data and serological inflammation markers. To assess variable associations and correct effects from confounding factors, we used a multiple linear regression approach. Results The deterioration of the motor and cognitive scores from visit 1 to visit 3 was not different in the pandemic group compared to the prepandemic group. 74.7 % of the pandemic PD patients had normal or high resilience scores, whereas 20.3% were at risk of developing PTSD. Resilience was neither correlated with motor scores nor with ...