Long-COVID patients may have altered metabolite levels upto two years after infection

The study led by researchers at the Autonomous University of Zacatecas in Mexico showed an alteration in levels of metabolites in long-COVID patients 2 years following the infection. Metabolites are products of metabolism, or the process of changing drink and food into energy that has cell-level roles such as providing defence, structure, or fuel.

Prolonged COVID-19 syndrome (also known as “long COVID”), which emerged as a consequence of the SARS-CoV-2 epidemic, is one of the major challenges currently faced by global health systems. About 30% of patients who have had COVID-19 are estimated to develop long COVID.

Yamilé López-Hernández, Autonomous University of Zacatecas, Zacatecas, Mexico, and colleagues aimed to evaluate the plasma metabolome in 100 samples collected from healthy controls, long COVID patients, and COVID-19 patients recruited in Mexico between 2020 and 2022.

For this purpose, they performed a targeted metabolomics approach using liquid chromatography and flow injection analysis with tandem mass spectrometry. to quantify 108 metabolites. Immunoenzymatic assay was used to measure IL-17 and weight-maintenance leptin in long COVID patients. All patients were fully vaccinated in 2021 and 2022. Six patients had mild COVID-19, 37 had moderate or severe infections, and 5 had critical cases.

The researchers reported the following findings:

· A comparison of paired samples from 15 COVID-19 and long-COVID patients showed significant differences in 53 metabolites, with 13 upregulated and 32 downregulated in long-COVID patients.

· Twenty-seven metabolites were still dysregulated in long-COVID patients compared with controls after 2 years. Long-COVID patients had different concentrations of lactic acid and arginine, altered lactate-pyruvate and ornithine-citrulline ratios, and significantly higher levels of IL-17.

· The most common long-COVID symptoms included memory loss (73.3%); sleep disorders, joint pain, fatigue, exercise intolerance, and muscle pain (66.7%); and anxiety (60.0%).

"Redox state imbalance, mitochondrial dysfunction, chronic immune dysregulation, and impaired energy metabolism are likely to be the main hallmarks of long COVID even after two years of acute COVID-19 infection," the researchers wrote.

According to them, metabolic information may partially explain the differences in disease presentation among long-COVID patients.

"Metabolomics is not only useful in providing a snapshot of transient pathophysiological or physiological processes taking place in a living organism, but it has also proven to be a powerful tool for proposing and monitoring therapeutic interventions," they wrote.

"The differences observed between the phenotypes of patients with post-COVID-19 reveal potential biomarkers that, once validated in larger and heterogeneous populations, and integrated with sociodemographic and clinical data, will enable a more precise and accurate classification of long COVID patients beyond classification via self-reported symptoms," they concluded.

Reference:

López, D. A., Zheng, J., Borrego, J. C., Pedro, J., Mandal, R., Berjanskii, M., López, J. A., & Wishart, D. S. (2023). The plasma metabolome of long COVID patients two years after infection. Scientific Reports, 13(1), 1-14. https://doi.org/10.1038/s41598-023-39049-x