Advances in medical technology and IT infrastructure have led to increased availability of continuous patient data that allows to investigate the longitudinal progression of novel and known diseases in unprecedented detail. However, to accurately describe any underlying pathophysiology with longitudinal data, the individual patient trajectories have to be synchronized based on temporal markers. In this study, we use longitudinal data from 28 critically ill ICU COVID-19 patients to compare the commonly used alignment markers "onset of symptoms", “hospital admission” and "ICU admission" with a novel objective method based on the peak value of inflammatory marker C-reactive protein (CRP). By applying our CRP-based method to align the progression of neutrophils and lymphocytes, we were able to define a pathophysiological window that allowed further mortality risk stratification in our COVID-19 patient cohort. Our data highlights that proper synchronization of patient data to the underlying pathophysiology is crucial to differentiate severity subgroups and to allow reliable interpatient comparisons.