Brazilian Plasma Metabolome Study Finds Massive Alterations In One-Carbon, Lipid, And Amino Acid Metabolism In Severe And Fatal COVID-19 Cases
Study found that choline-related metabolites, serine, glycine, and betaine, were reduced in severe COVID-19, as a result of dysregulation in methyl donors. Non-survivors had higher levels of creatine/creatinine,4-hydroxyproline, gluconic acid, and N-acetylserine, indicating liver and kidney dysfunction.
: The COVID-19 pandemic has cast its long shadow across the world, and Brazil has been one of the worst affected countries, grappling with a high death toll. Rio de Janeiro, a state known for its vibrant culture, has also faced the brunt of the virus. Even though vaccines have been introduced, the battle with COVID-19 is far from over, as it is expected to become an endemic disease. Understanding the molecular mechanisms behind the progression from mild to severe disease and the factors contributing to long COVID-19 has been an ongoing challenge for researchers.
Metabolic alterations in severe COVID-19. Summary of changes in plasma metabolites in survivors and non-survivors. Metabolites that differ significantly among groups are indicated as having higher (↑) or lower (↓) contents compared to controls. Metabolites in bold were higher in the fatal cases of the disease compared to survivors and controls. * indicates metabolites with changes greater in women than in men.
In a new study conducted by multiple prestigious Brazilian institutions, including Universidade Federal do Rio de Janeiro, Oswaldo Cruz Foundation, and Fundação Getúlio Vargas, among others, researchers explored the plasma metabolome of severe COVID-19 patients. Their findings shed light on major changes in one-carbon, lipid, and amino acid metabolism, as well as lipoprotein dynamics, in relation to the disease's severity and outcome.
The Complex Interplay of Metabolism and COVID-19 Pathophysiology
The replication of SARS-CoV-2, the virus responsible for COVID-19, triggers a systemic immune response that leads to tissue damage and a rewiring of the body's metabolism. Around 20% of infected individuals may experience long-term symptoms post-recovery, affecting multiple organ systems as covered in previous studies and COVID-19 News
. This complexity underscores the need for a comprehensive understanding of COVID-19 pathophysiology at the molecular level.
Studies have shown that coronaviruses, including SARS-CoV-2, modulate host lipid metabolism to facilitate viral RNA replication and assembly. Lipid droplets accumulate in monocytes isolated from COVID-19 patients, serving as platforms for viral particle assembly. The virus also orchestrates lipid flow within cells, essential for viral replication. Moreover, alterations in amino acid metabolism and inflammation markers have been observed in COVID-19 patients.
The Quest for Metabolic Clues in Severe COVID-19
To delve deeper into the metabolic alterations associated with severe COVID-19 and potential markers of fatal outcomes, the Brazilian study team employed cutting-edge techniques like Nuclear Magnetic Resonance (NMR) spectroscopy and Liquid Chromatography-High-Resolu
tion Mass Spectrometry (LC-HRMS) on a cohort of severe COVID-19 patients and healthy controls.
The results revealed significant changes in choline-related metabolites, serine, glycine, and betaine, indicating dysregulation in methyl donors. Notably, non-survivors showed higher levels of creatine/creatinine, 4-hydroxyproline, gluconic acid, and N-acetylserine, signifying potential liver and kidney dysfunction. These metabolic disturbances could serve as useful biomarkers to monitor organ health and understand the pathophysiology of acute and post-acute COVID-19 syndromes.
Unraveling the Role of One-Carbon Metabolism and Lipoprotein Dynamics
One-carbon metabolism, a vital pathway for cellular processes, showed significant disruptions in severe COVID-19 cases. Choline, a critical metabolite in this pathway, exhibited reduced levels in infected subjects. The study further identified the detrimental effects of lower choline availability on lipoprotein dynamics, affecting lipid metabolism and liver function.
Moreover, the study findings indicated a potential association between choline-related metabolites and liver and kidney damage, suggesting a disruption in one-carbon metabolism in severe cases. Notably, changes in lipoprotein dynamics were more pronounced in women, adding a new dimension to the understanding of COVID-19 sex-based differences.
Amino Acid Metabolism and Its Impact on Disease Severity
The study revealed lower levels of essential amino acids, such as alanine, BCAAs (valine, isoleucine, and leucine), glutamine, tryptophan, glycine, and tyrosine in COVID-19 patients compared to healthy controls. These alterations might be indicative of increased amino acid catabolism, necessary to support viral replication, and liver involvement in acute-phase protein synthesis.
Strikingly, the study found that the metabolic disturbances observed in COVID-19 patients differ based on the virus variant and the clinical presentation, highlighting the dynamic nature of the disease and its influence on metabolism.
Conclusions and Implications
The Brazilian Plasma Metabolome Study significantly contributes to our understanding of COVID-19 pathophysiology and the role of metabolism in disease severity. By identifying key metabolic alterations in severe cases, researchers can potentially develop biomarkers to monitor organ health and inform treatment strategies.
The findings also underscore the importance of considering sex-based differences in COVID-19 research, as they may influence disease outcomes and post-acute COVID-19 syndromes.
While the study acknowledges its limitations in sample size, it opens new avenues for research to explore metabolic pathways involved in severe COVID-19 and offers hope for better disease stratification and improved patient outcomes in the ongoing battle against the pandemic.
The study findings were published in the peer reviewed journal: Metabolites
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