The Ability to Normalise Energy Metabolism in Advanced COVID-19 Disease Seems to Be One of the Key Factors Determining the Disease Progression—A Metabolomic NMR Study on Blood Plasma

Abstract

Background: COVID-19 represents a severe inflammatory condition. Our work was designed to monitor the longitudinal dynamics of the metabolomic response of blood plasma and to reveal presumable discrimination in patients with positive and negative outcomes of COVID-19 respiratory symptoms. Methods: Blood plasma from patients, divided into subgroups with positive (survivors) and negative (worsening condition, non-survivors) outcomes, on Days 1, 3, and 7 after admission to hospital, was measured by NMR spectroscopy. Results: We observed changes in energy metabolism in both groups of COVID-19 patients; initial hyperglycaemia, indicating lowered glucose utilisation, was balanced with increased production of 3-hydroxybutyrate as an alternative energy source and accompanied by accelerated protein catabolism manifested by an increase in BCAA levels. These changes were normalised in patients with positive outcome by the seventh day, but still persisted one week after hospitalisation in patients with negative outcome. The initially decreased glutamine plasma level normalised faster in patients with positive outcome. Patients with negative outcome showed a more pronounced Phe/Tyr ratio, which is related to exacerbated and generalised inflammatory processes. Almost ideal discrimination from controls was proved. Conclusions: Distinct metabolomic responses to severe inflammation initiated by SARS-CoV-2 infection may serve towards complementary personalised pharmacological and nutritional support to improve patient outcomes.

1H qNMR-Based Metabolomics Discrimination of Covid-19 Severity

“…Previous publications on Covid-19 metabolomics support our findings once phenylalanine- and pyruvate-related metabolic pathways are described to be altered in different cohorts. 40 , 55 , 58 , 59 , 69 − 71 As discussed above, energy-related metabolic pathways, such as pyruvate metabolism, were shown to be relevant markers for symptom severity due to their close relation with viral replication and cytokine production.…”

Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients

“…3-Hydroxyisobutyrate in conditions of energy deficiency is a source of nourishment for the heart, brain, and muscles. It has been recently published that ketone bodies are unbalanced in subjects with COVID-19 and that their persistence at high levels in the blood was associated with a poor prognosis ( 42 – 44 ). In the OB– group, the unmodified levels of 3-Hydroxyisobutyrate suggest steady state compensatory mechanisms for altered glucose utilization or insulin resistance.…”

Applications and Challenges for Metabolomics via Nuclear Magnetic Resonance Spectroscopy

“…Our collection comprises four research articles that report interesting applications of NMR metabolomics in the biomedical setting. In the first article published in our issue, Baranovicova et al [3] present a longitudinal study that explores the dynamics of metabolomic changes in the plasma of 53 patients, diagnosed with SARS-CoV-2 infection, at three consecutive time points during their first week of hospitalization (days 1, 3, and 7 after admission to the hospital) to reveal the differences among patients with positive (survivors) and negative (worsening condition, non-survivors) outcomes. People with COVID-19, regardless their prognosis, presented alterations in their energy and amino acids metabolism.…”