The disease course and outcome of COVID-19 greatly varies between individuals. To explore which biological systems may contribute to this variation, we examined how individual metabolites and three metabolic scores relate to COVID-19 outcomes in hospitalized COVID-19 patients. The metabolome of 346 patients was measured using the 1H-NMR Nightingale platform. The association of individual metabolomic features and multi-biomarker scores, i.e. MetaboHealth, MetaboAge, and Infectious Disease Score (IDS) (higher scores reflect poorer health), with in-hospital disease course, long-term recovery, and overall survival were analyzed. Higher values for the metabolites phenylalanine (HR = 1.33, CI = 1.14-1.56), glucose (HR = 1.37, CI = 1.16-1.62) and lactate (HR = 1.38, CI = 1.16-1.63) were associated with mortality. For all three metabolic scores, higher scores were significantly associated with higher odds of a poorer in-hospital disease course (MetaboHealth: OR = 1.61, CI = 1.29-2.02; ΔMetaboAge: OR = 1.42, CI = 1.16-1.74; IDS: OR = 1.55, 1.25-1.93) and with overall survival (MetaboHealth: HR = 1.57, CI = 1.28-1.92; ΔMetaboAge: HR = 1.34, CI = 1.15-1.57; IDS: HR = 1.56, CI = 1.27-1.93). MetaboHealth and ΔMetaboAge showed a stronger association in younger patients (< 70 yrs.) than older patients. No clear patterns were found in associations between the three scores and measures of long-term recovery. In conclusion, the heterogeneity in disease course after SARS-COV2 infection may be explained either by generic biological frailty reflected by the three metabolomics scores or by glycemic control (glucose, lactate) and respiratory distress (phenylalanine).

© 2025. The Author(s).