## 5 Conclusions  
Metabolomic changes in blood plasma analysed by NMR in patients suffering COVID-19 were strong enough to obtain almost ideal discrimination from controls, where the ROC derived from random forest showed an AUC of 0.995 for the variables 3-hydroxybutyrate, phenylalanine, acetate, glucose, and Phe/Tyr ratio. The inflammation by COVID-19 caused changes in the body's energy metabolism, where we observed increased blood glucose that implies lowered glucose utilisation, balanced with increased production of 3-hydroxybutyrate as an alternative energy source. Besides that, increased essential BCAAs are a sign of accelerated protein catabolism, offering a further energy source. Interestingly, although all COVID-19-positive patients received dexamethasone treatment during the follow-up period, the above mentioned changes (increased glucose, 3-hydroxybutyrate, and BCAAs levels in blood plasma) normalised only in patients with positive outcome by the seventh day; however, they persisted for over one week in patients with negative outcome (more than half of them had died at the time of writing). Further, patients suffering COVID-19 showed decreased plasma glutamine that normalised faster in patients with a positive outcome. With the length of hospital stay, plasma levels of creatine increased in patients in both groups. Increased Phe/Tyr ratio, which is closely connected with neuropsychiatric morphologies, often reported as post-COVID-19 symptoms, was more pronounced in patients with a negative outcome. Based on our results, the ability of patients to normalise energy metabolism seems to be one of the key factors determining the disease progression. This trend was observed independently of patient diet, which differed with respect to diabetic condition. This study documents evident differences in the course of the metabolomic response to COVID-19 in relation to patient outcome. However, the described changes may not be unique for COVID-19 since they reflect generalised immune response and alterations in body energy metabolism as well. The presented results may serve towards complementary personalised pharmacological and nutritional support in order to improve patient outcomes in severe inflammatory conditions. Figure 4: Relative concentrations of selected metabolites related to immunity in blood plasma for patient Groups A and B on Day 1, Day 3, and Day 7. Values are relativised to the median of controls given a value of 1. **Supplementary Materials:** The following are available online at [[https://www.mdpi.com/article/10.3390/app11094231/s1](https://www.mdpi.com/article/10.3390/app11094231/s1)]([https://www.mdpi.com/article/10.3390/app11094231/s1](https://www.mdpi.com/article/10.3390/app11094231/s1)), Figure S1: PCA (left) and PLD-DA analyses (right) of the system of patients divided into subgroups Group A and Group B on Day 1 versus controls; algorithms were fed relative concentrations of plasma metabolites, and analyses were run in metaboanalyst [16]. Figure S2. The relative changes in two metabolites closely related to energy metabolism--glucose and 3-hydroxybutyrate--where both Groups A and B were divided into subgroups according to patient diet (according to presence of diabetes) on Days 1, 3, and 7 after hospital arrival; not dia = non-diabetic patients on a normal diet, dia = diabetic patients on a diabetic diet. Values were relativized to median of controls set to 1. **Author Contributions:** Conceptualization, E.B., A.B., R.V., V.N. and J.L. ; methodology, E.B. ; formal analysis, E.B. ; investigation, E.B., Z.D. and J.L. ; data curation, E.B., A.B., R.V., Z.D. and J.L. ; writing--original draft preparation, E.B., writing--review and editing, A.B., E.H., V.N. and J.L. ; supervision, J.L. ; funding acquisition, J.L. All authors have read and agreed to the published version of the manuscript.