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Background Medical students’ propensity to develop mental morbidity has been described for decades but remains unresolved. To assess student mental health person-centred and longitudinally, we have been investigating a cohort of German students since October 2019. After their first semester under ‘normal’ conditions, rapid changes became necessary due to the COVID-19 situation. In line with the initial aim, we investigated students’ change of mental health, perceived learning environment and burdens in the ‘new normal’. Methods Students in a newly founded German medical study programme (n = 63) answered a questionnaire each semester (October 2019 = entering medical school; December 2019 = ‘old normal’; June 2020 = ‘new normal’; December 2020 = ‘new normal’) on their well-being (FAHW-12), burnout (Maslach Inventory), depression (PHQ-9), perception of the learning environment (DREEM), burdens and protective attitudes in the ‘new normal’ (items designed for the study). Results Friedman tests reveal overall significant differences (all p < .001) in depression and burnout (emotional exhaustion, depersonalisation, personal accomplishment); changes in well-being were identified as just non-significant (p = .05). The effects were explained by a significant increase in burnout and depression identified post-hoc from October 2019 to December 2019. No increase in severity was identified in the ‘new normal’ semesters. The learning environment was perceived positively even with a significant improvement for June 2020 (repeated measures ANOVA p < .001). Study-related burdens (e.g. procrastination of online-learning material) took on greater relevance than burdens related to physicians’ occupation (e.g. potential for students' recruitment to the healthcare system during their studies). Conclusions The ‘new’ when entering medical school had a greater impact on our students’ mental health than the ‘new normal’. The readiness for change in the context of a newly designed study programme may have been beneficial with regard to students’ positively perceived learning environment during the virtual semesters. Monitoring medical students’ mental health longitudinally should be a concern regardless of a pandemic.

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