COVID-19 can range from a mild to severe acute respiratory syndrome and also could result in multisystemic damage. Additionally, many people develop post-acute symptoms associated with immune and metabolic disturbances in response to viral infection, requiring longitudinal and multisystem studies to understand the complexity of COVID-19 pathophysiology. Here, we conducted a ¹H Nuclear Magnetic Resonance metabolomics in saliva of symptomatic subjects presenting mild and moderate respiratory symptoms to investigate prospective changes in the metabolism induced after acute-phase SARS-CoV-2 infection. Saliva from 119 donors presenting non-COVID and COVID-19 respiratory symptoms were evaluated in the acute phase (T1) and the post-acute phase (T2). We found two clusters of metabolite fluctuation in the COVID-19 group. Cluster 1, metabolites such as glucose, (CH₃)₃ choline-related metabolites, 2-hydroxybutyrate, BCAA, and taurine increased in T2 relative to T1, and in cluster 2, acetate, creatine/creatinine, phenylalanine, histidine, and lysine decreased in T2 relative to T1. Metabolic fluctuations in the COVID-19 group were associated with overweight/obesity, vaccination status, higher viral load, and viral clearance of the respiratory tract. Our data unveil metabolic signatures associated with the transition to the post-acute phase of SARS-CoV-2 infection that may reflect tissue damage, inflammatory process, and activation of tissue repair cascade. Thus, they contribute to describing alterations in host metabolism that may be associated with prolonged symptoms of COVID-19.

Background: The placenta plays a central role in the metabolic adaptations required for a healthy pregnancy and its dysfunction contributes to Gestational Diabetes Mellitus (GDM) development. We explored the placental metabolic profile, particularly metabolites of one-carbon metabolism, in GDM pregnancies and its association with maternal dietary methyl donor intake and neonatal outcomes. Methods: Dietary records were obtained from a prospective cohort with pregnant women. Groups were divided into control (n=13) and GDM (n=11). A subset of placental samples collected at delivery (control n=6; GDM n=5) was used for MS and NMR-based metabolomics. Results: Dietary intake was similar between the groups as well as the sum of dietary methyl donors (choline, betaine and methionine). Importantly, 100% of women presented with inadequate dietary choline. Placentas from pregnancies affected by GDM presented lower levels of choline, serine, glycine and SAM, despite good glycemic control and the absence of adverse neonatal outcomes. Conclusion: While the placenta demonstrated adaptive mechanisms that possibly mitigated placental stress, the long-term implications of these adaptations on offspring health remain uncertain. Given the critical role of methyl donors in epigenetic regulation and fetal programming, further research is needed to refine dietary guidelines, potentially guiding more tailored nutritional interventions focusing on choline supplementation during pregnancy.