The Urinary Metabolome of Newborns with Perinatal Complications.

Maternal pathological conditions such as infections and chronic diseases, along with unexpected events during labor, can lead to life-threatening perinatal outcomes. These outcomes can have irreversible consequences throughout an individual's entire life. Urinary metabolomics can provide valuable insights into early physiological adaptations in healthy newborns, as well as metabolic disturbances in premature infants or infants with birth complications. In the present study, we measured 180 metabolites and metabolite ratios in the urine of 13 healthy (hospital-discharged) and 38 critically ill newborns (admitted to the neonatal intensive care unit (NICU)). We used an in-house-developed targeted tandem mass spectrometry (MS/MS)-based metabolomic assay (TMIC Mega) combining liquid chromatography (LC-MS/MS) and flow injection analysis (FIA-MS/MS) to quantitatively analyze up to 26 classes of compounds. Average urinary concentrations (and ranges) for 167 different metabolites from 38 critically ill NICU newborns during their first 24 h of life were determined. Similar sets of urinary values were determined for the 13 healthy newborns. These reference data have been uploaded to the Human Metabolome Database. Urinary concentrations and ranges of 37 metabolites are reported for the first time for newborns. Significant differences were found in the urinary levels of 44 metabolites between healthy newborns and those admitted at the NICU. Metabolites such as acylcarnitines, amino acids and derivatives, biogenic amines, sugars, and organic acids are dysregulated in newborns with bronchopulmonary dysplasia (BPD), asphyxia, or newborns exposed to SARS-CoV-2 during the intrauterine period. Urine can serve as a valuable source of information for understanding metabolic alterations associated with life-threatening perinatal outcomes.

The plasma metabolome of long COVID patients two years after infection.

One of the major challenges currently faced by global health systems is the prolonged COVID-19 syndrome (also known as "long COVID") which has emerged as a consequence of the SARS-CoV-2 epidemic. It is estimated that at least 30% of patients who have had COVID-19 will develop long COVID. In this study, our goal was to assess the plasma metabolome in a total of 100 samples collected from healthy controls, COVID-19 patients, and long COVID patients recruited in Mexico between 2020 and 2022. A targeted metabolomics approach using a combination of LC-MS/MS and FIA MS/MS was performed to quantify 108 metabolites. IL-17 and leptin were measured in long COVID patients by immunoenzymatic assay. The comparison of paired COVID-19/long COVID-19 samples revealed 53 metabolites that were statistically different. Compared to controls, 27 metabolites remained dysregulated even after two years. Post-COVID-19 patients displayed a heterogeneous metabolic profile. Lactic acid, lactate/pyruvate ratio, ornithine/citrulline ratio, and arginine were identified as the most relevant metabolites for distinguishing patients with more complicated long COVID evolution. Additionally, IL-17 levels were significantly increased in these patients. Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection.

The Urinary Metabolome of Healthy Newborns.

The knowledge of normal metabolite values for neonates is key to establishing robust cut-off values to diagnose diseases, to predict the occurrence of new diseases, to monitor a neonate's metabolism, or to assess their general health status. For full term-newborns, many reference biochemical values are available for blood, serum, plasma and cerebrospinal fluid. However, there is a surprising lack of information about normal urine concentration values for a large number of important metabolites in neonates. In the present work, we used targeted tandem mass spectrometry (MS/MS)-based metabolomic assays to identify and quantify 136 metabolites of biomedical interest in the urine from 48 healthy, full-term term neonates, collected in the first 24 h of life. In addition to this experimental study, we performed a literature review (covering the past eight years and over 500 papers) to update the references values in the Human Metabolome Database/Urine Metabolome Database (HMDB/UMDB). Notably, 86 of the experimentally measured urinary metabolites are being reported in neonates/infants for the first time and another 20 metabolites are being reported in human urine for the first time ever. Sex differences were found for 15 metabolites. The literature review allowed us to identify another 78 urinary metabolites with concentration data. As a result, reference concentration values and ranges for 378 neonatal urinary metabolites are now publicly accessible via the HMDB.