The Divergent Metabolomic Landscape of COVID-19 and Community-Acquired Pneumonia.

OBJECTIVES

To map and compare the serum metabolome of hospitalized patients with COVID-19 or community-acquired pneumonia (CAP).

DESIGN

Observational matched cohort study using an untargeted metabolomics approach.

SETTING

Serum samples were obtained at the time of hospital admission as part of two clinical trials conducted in hospitalized patients.

PATIENTS

A matched cohort design was applied, including patients with COVID-19 and CAP, matched according to age, sex, and Charlson Comorbidity Index. The patient samples were obtained from two clinical studies, namely the suPAR-guided Anakinra Treatment for Validation of the Risk and Management of Respiratory Failure by COVID-19 (SAVE) trial (ClinicalTrials.gov identifier: NCT04357366; European Union Drug Regulating Authorities (EudraCT) number: 2020-001466-11) and the A randomized clinical trial of oral Clarithromycin in Community-acquired pneumonia to attenuatE inflammatory responseS and improve outcomeS (ACCESS trial) (ClinicalTrials.gov identifier: NCT04724044; EudraCT number: 2020-004452-15). The total study population comprised 92 patients.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

A total of 3555 metabolites were detected, and differential analysis recovered more than 70% of the metabolome as altered between conditions. Metabolite pathway analysis highlighted pathways related to the citric acid cycle and arachidonic metabolism as activated in CAP, while COVID-19 was mainly driven by alterations in amino acid metabolism and metabolites related to mitochondrial function.

CONCLUSIONS

Extensive divergence was observed in the metabolomic landscape of patients with COVID-19 or CAP, underscoring the disease-specific metabolic adaptations and providing potential targets for diagnostic and therapeutic development.

Copyright © 2026 The Authors. Published by Wolters Kluwer Health, LLC. on behalf of the Society of Critical Care Medicine.