AimThe COVID-19 pandemic represented a great disturbance for medical systems around the world, putting medical personnel on the front lines of the fight against the SARS-Cov2 virus. This fight was particularly impactful in countries with medical systems already facing various challenges, including Romania; where the pandemic unfolded in five waves that severely affected the psychological and physical well-being of medical professionals in terms of overload and continuous exposure to health threats. Against this background, our research aims to identify the mediating role of potential affecting factors of healthcare work sustainability during the change-related uncertainty conditions generated by the COVID 19 crisis. Dynamics and relations of nine carefully selected constructs were tracked along all five pandemic waves in Romania, which span from March 2020 to April 2022. The tested variables and constructs are perception of healthcare workers of their own state of health, their workplace safety, the work–family conflict, the satisfaction of basic needs, the work meaningfulness and work engagement, patient care, pandemic stress and burnout.MethodsThis cross-sectional study is based on an online snowball sampling of 738 health workers from 27 hospitals. Panel research is limited to a maximum of 61 respondents for two successive waves. The analytical part is built on means comparison of analysed variables between all five pandemic waves and an in-depth model to explain the relationships between the variables.ResultsThe results indicate statistically significant correlations between the perception of health risks and all selected factors excluding patient care, which seems to be above the own health perception. The factors’ dynamics was followed along all five pandemic waves. The developed model identified that one’s health status satisfaction is a mediator of the family–work conflict and, together, of work engagement. In turn, work engagement plays a significant role in satisfying basic psychological needs and supporting work meaningfulness. Also, work meaningfulness influences the satisfaction of basic psychological needs.DiscussionHealth workers with higher levels of positive perceived health are better at managing pandemic stress, burnout effects and work-family imbalances. Adaptive behaviors and attitudes towards COVID-19 pandemic threats could be identified in later pandemic waves due to the progress in terms of medical protocols and procedures.