Promising Markers of Inflammatory and Gut Dysbiosis in Patients with Post-COVID-19 Syndrome

Abstract

Post-COVID-19 syndrome is a complex of different symptoms, which results in a multisystemic impairment after the suffering from COVID-19 infection. The aim of the study was to reveal the clinical, laboratory, and gut disorders in patients with post-COVID-19 syndrome (n = 39) before and after taking part in the 14-day complex program of rehabilitation. A complete blood count, coagulation test, blood chemistry, biomarkers, and metabolites in serum samples, and gut dysbiosis were revealed in patients on the day of admission and after 14-day rehabilitation, in comparison with the variables of healthy volunteers (n = 48) or with reference ranges. On the day of discharge, patients noted an improvement in respiratory function, general well-being, and mood. At the same time, the levels of some metabolic (4-hydroxybenzoic, succinic, fumaric acids) and inflammatory (interleukin-6) variables, which were increased on admission, did not reach the level of healthy people during the rehabilitation program. Taxonomy disbalance was observed in patients’ feces, namely, a high level of total bacterial mass, a decrease in the number of Lactobacillus spp., and an increase in pro-inflammatory microorganisms. The authors suggest that the post-COVID-19 rehabilitation program should be personalized, considering the patient’s state together with not only the baseline levels of biomarkers, but also with the individual taxonomy of the gut microbiota.

Analysis of 4-Hydroxyphenyllactic Acid and Other Diagnostically Important Metabolites of α-Amino Acids in Human Blood Serum Using a Validated and Sensitive Ultra-High-Pressure Liquid Chromatography-Tandem Mass Spectrometry Method

“…In a 2018 study, the median reference concentration of PhPA and p-HPhLA obtained using GC-MS in serum samples of 40 healthy volunteers was 0.5 µmol/L [4]. In a recent study, the data also obtained using GC-MS on the same 48 healthy volunteers as in our study (Table 3) demonstrated the presence of PhPA, PhLA, p-HPhAA, and p-HPhLA in serum samples with different frequencies [6]. Only p-HPhLA was measured in all 48 samples.…”

“…We have previously demonstrated that a number of metabolites of aromatic α-amino acids are ubiquitous, and their low serum concentrations reflect the integration of the human metabolism with its microbiota [4]. Some of the metabolites can be used as prognostic markers of infectious complications and outcomes in severe patients with various pathologies [5] and in patients with post-COVID-19 syndrome [6]. These metabolites include phenyl-containing microbial and endogenous derivatives of phenylalanine (phenyllactic (PhLA) and phenylpropionic (PhPA) acids) and tyrosine (4-hydroxyphenyllactic (p-HPhLA), 4-hydroxyphenylacetic (p-HPhAA), 4-hydroxybenzoic (p-HBA), and 4-hydroxyphenylpropionic (p-HPhPA) acids).…”

“…These metabolites include phenyl-containing microbial and endogenous derivatives of phenylalanine (phenyllactic (PhLA) and phenylpropionic (PhPA) acids) and tyrosine (4-hydroxyphenyllactic (p-HPhLA), 4-hydroxyphenylacetic (p-HPhAA), 4-hydroxybenzoic (p-HBA), and 4-hydroxyphenylpropionic (p-HPhPA) acids). These compounds, both together and separately (in particular, p-HPhLA), were used to build predictive models in blood serum and cerebrospinal fluid using liquid-liquid extraction or microextraction via packed sorbent coupled with gas chromatography-mass spectrometry (GC-MS) [4][5][6]. The study that has described the results of a univariate model using p-HPhLA and two multivariate classification models is of particular interest, because it has demonstrated that aromatic metabolites (one or a number of them) can be used in clinical practice for the prognosis of the outcomes of critically ill patients on the day of admission to the intensive care unit [5].…”

Longitudinal NMR-Based Metabolomics Study Reveals How Hospitalized COVID-19 Patients Recover: Evidence of Dyslipidemia and Energy Metabolism Dysregulation

“…In a hypoxic state, there is a burden of glucose production (gluconeogenesis) and urea elimination (the urea cycle) in the liver. A recently published study of 39 post-COVID-19 patients in rehabilitation also found high levels of succinic and fumaric acids (TCA cycle metabolites) and associated these observations with hypoxia and inflammation [44]. Although analyzing drug metabolites was out of this study's scope, a notable fact is that corticosteroids, especially dexamethasone, were used for the treatment of severe COVID-19, and corticosteroids increase hepatic gluconeogenesis, reduce peripheral use of glucose, and increase insulin levels, contributing to hyperglycemia in patients.…”

In Vitro Fermentation Characteristics of Fungal Polysaccharides Derived from Wolfiporia cocos and Their Effect on Human Fecal Microbiota

“…Significant alteration in gut microbiota composition is often observed in diseased patients. Such dysbiosis is even described as a potential microbial biomarker for precision medicine [15][16][17]. Indigestible food remains in the colon could be a potential substrate for gut microbes.…”