COVID-19 News: Study Of Long-Term Metabolic Alterations In Recovered SARS-CoV-2 Patients Reveals Up To 170 Dysregulations Two Years On!

COVID-19 News: A new study by researchers from University of Zacatecas-Mexico, Instituto Mexicano del Seguro Social-Mexico, Waters Technologies of Brazil, Waters Corporation-Mexico and University of Monterrey-Mexico has alarmingly found that up to 170 metabolic dysregulations were found in recovered SARS-CoV-2 patients two years on….. especially dysregulated lipid pathways.


 
According to the study team, similar to what it has been reported with preceding viral epidemics (such as MERS, SARS, or influenza), SARS-CoV-2 infection is also affecting the human immunometabolism with long-term consequences.
 
The study team aimed to evaluate the clinical and lipidomic profiles (using non-targeted lipidomics) of recovered patients who had a mild and severe COVID-19 infection (acute phase, first epidemic wave); the assessment was made two years after the initial infection.
 
Alarmingly, functional analyses revealed that sterols, bile acids, isoprenoids, and fatty esters were the predicted metabolic pathways affected in both COVID-19 and post-COVID-19 patients.
 
Principal Component Analysis showed differences between study groups. Several species of phosphatidylcholines and sphingomyelins were identified and expressed in higher levels in post-COVID-19 patients compared to controls.
 
Shockingly, the paired analysis (comparing patients with an active infection and 2 years after recovery) show 170 dysregulated features. The relationship of such metabolic dysregulations with the clinical symptoms, point to the importance of developing diagnostic and therapeutic markers based on cell signaling pathways.
 
The study findings were published in the peer reviewed journal: Frontiers In Biomolecular Sciences.
https://www.frontiersin.org/articles/10.3389/fmolb.2023.1100486/full
 
Past COVID-19 News coverages had also shown that SARS-CoV-2 infections impairs lipid pathways.
https://www.thailandmedical.news/news/breaking-sars-cov-2-impairs-lipid-metabolic-and-autophagic-pathways,-causing-damage-to-heart,-liver-and-kidneys-the-phytochemical-trigonelline-helps
 
https://www.thailandmedical.news/news/austrian-multi-omics-study-discovers-unique-anti-inflammatory-immune-signature-and-metabolic-alterations-in-individuals-with-long-covid
 
https://www.thailandmedical.news/news/sars-cov-2-research-study-finds-that-mutations-on-orf3a-determines-sars-cov-2-viral-fitness-through-modulation-of-lipid-droplets
& nbsp;
https://www.thailandmedical.news/news/covid-19-supplements-yale-study-shows-lipidomic-changes-that-mark-covid-19-disease-severity-resolvins-from-omega-3-fatty-acids-could-help
 
This extensive study aimed to thoroughly examine the clinical and metabolic changes that persist in patients two years after experiencing a SARS-CoV-2 infection of varying severity levels. The dysregulated metabolic pathways observed during infection and after two years of recovery were identified using a functional analysis approach. This approach assumes that putative annotation at the individual compound level can collectively predict changes at functional levels, as demonstrated by a past study.
https://pubmed.ncbi.nlm.nih.gov/23861661/
 
Dysregulated Lipid Classes in COVID-19 Patients
Lipid classes such as sterols, steroids, and fatty esters were found to be dysregulated in both COVID-19 patient groups studied.
 
A study recently discovered higher levels of poly and highly unsaturated fatty acids in patients with post-COVID-19 syndrome (more than 28 days after infection: recruitment phase conducted within a two-year time interval). This finding aligns with reduced fatty acid oxidation at the mitochondrial level. The accumulation of such molecules has been linked to erythrocyte dysfunction and impaired oxygen transportation, which could persist for months, potentially explaining symptoms like fatigue and exercise intolerance.
https://pubmed.ncbi.nlm.nih.gov/36355108/
 
Sterols And Cholesterol
Sterols are a subgroup of steroids, with cholesterol being the most well-known type. Cholesterol is crucial for membrane structure and serves as a precursor for fat-soluble vitamins and steroid hormones. A recent systematic review and meta-analysis demonstrated that lower concentrations of total HDL and LDL-cholesterol were significantly associated with COVID-19 severity and mortality, suggesting that cholesterol concentrations might be useful for risk stratification and monitoring.
https://pubmed.ncbi.nlm.nih.gov/34490188/
 
However, another study recently demonstrated that the lipoproteome of recovered patients gradually reverted to a healthy state.
https://pubmed.ncbi.nlm.nih.gov/35446921/
 
Corticosteroids
Corticosteroids, such as dexamethasone, are classified as steroids and exhibit significant anti-inflammatory and anti-fibrotic effects. These effects may play a role in reducing lung and systemic inflammation, particularly in severe pneumonia and advanced stages of COVID-19. Even these were found to be dysregulated in COVID-19 patients.
https://pubmed.ncbi.nlm.nih.gov/35090528/
 
Fatty Esters: Monoacylglycerols, Diacylglycerols, And Triacylglycerols
Fatty esters, including monoacylglycerols, diacylglycerols, and especially triacylglycerols, have also been linked to metabolic dysregulation in COVID-19 patients.
https://pubmed.ncbi.nlm.nih.gov/33785815/
 
Bile Acid
Bile acids, which are signaling molecules involved in immune, metabolic, and intestinal microbiota control actions, were also found to be dysregulated in COVID-19 patients.
https://pubmed.ncbi.nlm.nih.gov/27320064/
 
Bile acid pathways have been widely reported in COVID-19 due to the established association between gut dysbiosis and inflammatory processes leading to severe disease. However, abnormalities in bile acid metabolism are also connected to liver injury and the cholesterol transport system, both common in severe COVID-19 cases.
https://pubmed.ncbi.nlm.nih.gov/32492406/
 
Disordered bile acid metabolism has been documented in recovered COVID-19 patients (three months after discharge), suggesting that intestinal equilibrium at the mucosal level is delayed before being fully repaired.
https://pubmed.ncbi.nlm.nih.gov/34522117/
 
Isoprenoids 
In post-COVID-19 patients, the isoprenoids pathway, also known as the mevalonate pathway, has been observed to be dysregulated. The isoprenoids pathway is an essential metabolic pathway in cells, responsible for the biosynthesis of various isoprenoid compounds, such as cholesterol, coenzyme Q10, and other essential molecules involved in cellular processes. These molecules play critical roles in cellular signaling, membrane integrity, and energy production.
https://pubmed.ncbi.nlm.nih.gov/15357017/
 
Dysregulation of the isoprenoid pathway in post-COVID-19 patients could have several potential consequences for their health:
 
-Altered cholesterol synthesis: Cholesterol is a vital component of cell membranes and a precursor for the synthesis of steroid hormones, bile acids, and vitamin D. A dysregulated isoprenoids pathway could result in abnormal cholesterol synthesis, which might contribute to a variety of health issues, including cardiovascular complications and hormonal imbalances.
 
-Impaired coenzyme Q10 production: Coenzyme Q10 (CoQ10) is an essential component of the mitochondrial electron transport chain, which plays a crucial role in energy production within cells. Reduced CoQ10 levels due to isoprenoids pathway dysregulation could lead to diminished cellular energy production, which may contribute to the persistent fatigue reported by many post-COVID-19 patients.
 
-Abnormal cellular signaling: Isoprenoids, such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate, are involved in the post-translational modification of proteins known as prenylation. Prenylated proteins are involved in various cellular signaling pathways that regulate processes such as cell growth, differentiation, and apoptosis. Dysregulation of the isoprenoid pathway could lead to abnormal prenylation, potentially disrupting essential cellular processes and contributing to the lingering symptoms experienced by Long-COVID individuals.
 
-Increased oxidative stress: Some isoprenoids function as antioxidants, protecting cells from oxidative stress by neutralizing reactive oxygen species. Dysregulation of the isoprenoid pathway could lead to decreased antioxidant capacity, which may exacerbate oxidative stress and inflammation in post-COVID-19 patients. This could contribute to the ongoing inflammation and tissue damage observed in some individuals recovering from the infection.
 
Understanding the molecular mechanisms behind the dysregulation of the isoprenoids pathway in post-COVID-19 patients is crucial for developing targeted therapies to address the long-term health consequences of the infection. Further research is needed to elucidate the precise molecular changes in the isoprenoids pathway and to identify potential therapeutic targets to restore normal cellular function.
 
Future studies should also investigate the interplay between the isoprenoids pathway and other metabolic pathways that may be affected in post-COVID-19 patients.
 
Acylcarnitines, Glycerophospholipids, Phosphatidylcholines And Sphingolipids Also Dsyregulated.
 
In this study, lipid metabolism was found to be altered in all stages of SARS-CoV-2 infection and recovery. Altered levels of acylcarnitines, glycerophospholipids, and unsaturated fatty acids were observed in early onset symptoms, during hospitalization, and months after discharge. The dysregulation of lipids was associated with long-term chronic discomfort and immune dysregulation in COVID-19 survivors.
 
Phosphatidylcholines were found to be altered, with a complex regulation depending on factors like infection severity, immune status, and comorbidities. The observed dysregulation could be due to compensatory mechanisms, persisting molecular mechanisms, cross-talking with the immune system and gut microbiota, or lifestyle changes.
 
Sphingolipids, involved in processes such as inflammation and cellular differentiation, were also dysregulated. This could be associated with symptoms like fatigue and muscular pain, as sphingolipids are known to affect skeletal muscle cells. Increased sphingolipid levels have been observed in metabolic syndrome and the acute cell danger response.
 
In summary, the study found that lipid metabolism was altered in COVID-19 patients throughout the infection and recovery process. This dysregulation could be linked to immune dysregulation, chronic discomfort, and symptoms like fatigue and muscle pain.
 
It is important to mention that this study focused primarily on the lipidomic profile of patients, which may not provide a comprehensive understanding of the full range of metabolic alterations that persist after a SARS-CoV-2 infection.
 
Alterations in lipids have been found in recovered patients from SARS (2003). A past study that followed 25 recovered SARS patients 12 years after infection found increased levels of phosphatidylinositol and lysophosphatidylinositol.
https://pubmed.ncbi.nlm.nih.gov/28831119/
 
Future studies should also explore other metabolic pathways and integrate additional omics data, such as proteomics and transcriptomics, to obtain a more holistic understanding of the long-term impacts of COVID-19 on the human body.
 
The study provides valuable insights into the long-term metabolic alterations that persist in patients who have recovered from a SARS-CoV-2 infection. These findings highlight the need for ongoing research to better understand the long-term consequences of COVID-19 and to develop effective strategies to support patients in their recovery.
 
In conclusion, this study has demonstrated that even two years after a SARS-CoV-2 infection, patients exhibit persistent metabolic alterations, particularly in lipid pathways. These alterations could explain some of the lingering symptoms experienced by post-COVID-19 patients, such as fatigue and musculoskeletal issues.
 
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