LATEST! Individuals With Elevated Levels Of Acid Ceramidase And Sphingosine In Blood Likely To Become Asymptomatic When Infected With SARS-CoV-2!

A new ground breaking study led by oncology researchers from the Medical University of South Carolina has found that individuals with elevated levels of the lipid Sphingosine and a protein that it involved in its production called Acid Ceramidase (AC) in their blood were most likely to become asymptomatic when infected with the SARS-CoV-2 coronavirus. However the study also found that those that had reduced levels of these two compounds were found to become symptomatic.

 
Bioactive sphingolipids play a crucial role in the regulation of viral infections and pro-inflammatory responses involved in the severity of COVID-19.
 
To date however, any roles of sphingolipids in COVID-19 development or detection remain unknown.
 
Based on the study findings, lipidomics measurement of serum sphingolipids demonstrated that reduced sphingosine levels are highly associated with the development of symptomatic COVID-19 in the majority (99.24%) SARS-CoV-2-infected patients compared to asymptomatic counterparts. The majority of asymptomatic individuals (73%) exhibited increased acid ceramidase (AC) in their serum, measured by Western blotting, consistent with elevated sphingosine levels compared to SARS-CoV-2 antibody negative controls. AC protein was also reduced in almost all of the symptomatic patients’ serum, linked to reduced sphingosine levels, measured in longitudinal acute or convalescent COVID-19 samples.
 
The study findings showed that reduced sphingosine levels provide a sensitive and selective serologic biomarker for the early identification of asymptomatic versus symptomatic COVID-19 patients.
 
The study findings were published in the peer reviewed journal: Scientific Reports. https://www.nature.com/articles/s41598-021-93857-7
 
Often, researchers remain perplexed as to why some patients infected with SARS-CoV-2, the coronavirus responsible for COVID-19, remain asymptomatic while other patients develop severe disease symptoms.
 
This key question is once again at the front of the minds of many experts as the Delta variant spreads across the globe.
 
The study team discovered a specific and sensitive biomarker in blood samples that predicts which patients will develop COVID-19 symptoms.

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Their study findings show that reduced levels of a specific lipid, sphingosine, are significantly associated with developing COVID-19 symptoms. Conversely, elevated levels of sphingosine, as well as a protein involved in its production, acid ceramidase (AC), are associated with asymptomatic infections.
 
Dr Besim Ogretmen, Ph.D., Director of the Lipidomics Shared Resource at Hollings Cancer Center and Leader of the Hollings Developmental Cancer Therapeutics Research Program at the Medica l University of South Carolina told Thailand Medical News, “We developed this project at a time when there wasn't a successful vaccine. We wanted to contribute to the field and know which patients who were exposed to this virus would be symptomatic versus asymptomatic."
 
In the past 19 months several waves of SARS-CoV-2 infections in the world have resulted in more than 204 million SARS-CoV-2 infections and almost 4.4 million COVID-19 deaths. Despite the development of multiple safe and effective vaccines, the world is currently experiencing another wave of infections.
 
Importantly the mortality of COVID-19 is thought to result from an overactive immune response to the virus in the lungs of infected patients that causes severe respiratory distress. However, symptoms vary widely, and scientists and clinicians don't understand why some patients develop severe symptoms while others remain asymptomatic.
 
Interestingly it is known that sphingolipids, a class of molecules that are important for the integrity of the cell membrane and communication between cells, can regulate inflammation and the immune system in response to various infections.
 
The Ogretmen laboratory has decades of expertise in analyzing the production and processing of different lipids, including sphingolipids, using a global measurement method called lipidomics.
 
Utilizing this expertise, the Ogretmen lab undertook an unbiased analysis of COVID-19 patient serum samples from the MUSC COVID-19 Biorepository to look for changes in sphingolipid levels. The study findings turned out to be interesting.
 
Alhaji Janneh, lead author and graduate student in the Department of Biochemistry and Molecular Biology at the Medical University of South Carolina added, "Just by looking at the data, you can clearly separate the different patient groups, even without doing technical statistical analyses."
 
Importantly in asymptomatic patients who tested positive for a SARS-CoV-2 antibody, the study team found a slight increase in serum sphingosine levels and only sphingosine compared to patients who tested negative.
 
Remarkably, in patients who developed COVID-19 symptoms, there was a 15-fold reduction in sphingosine levels.
 
Conversely, almost 75% of asymptomatic patients had elevated AC levels while most symptomatic patients had no detectable AC. The presence of serum AC correlates with the increased levels of sphingosine.
 
Dr Ogretmen, who is also a professor in the Department of Biochemistry and Molecular Biology and the SmartState Endowed Chair in Lipidomics and Drug Discovery commented, "Can this be an alternative way to predict which patients are the most vulnerable to severe disease? If we can separate asymptomatic patients from symptomatic patients, we can use limited remedies and resources for patients who are more vulnerable."
 
The study finding showed that there is a 99% probability of correctly determining which patients, who have tested positive for SARS-CoV-2 antibodies, will develop disease symptoms versus remain asymptomatic, using blood levels of sphingosine.
 
The study team added that these striking results would not have been possible without the MUSC COVID-19 Biorepository and collaboration with the South Carolina Clinical & Translational Research Institute (SCTR). SCTR set up the biorepository to serve as a resource for COVID-19 research, and SCTR co-principal investigator Dr Patrick Flume, M.D. is its director and one of the authors of the study.
 
It must be noted that analyzing levels of various lipids from patient samples is expensive and requires sophisticated equipment, making this type of analysis prohibitive under most circumstances. However, the development of an ELISA-based assay - like those used to diagnose HIV infection - to detect levels of AC could provide a cost-effective alternative that could be widely implemented.
 
Importantly there are several outstanding questions remaining. How does vaccination impact sphingosine levels? How do sphingosine levels change with the introduction of more variants? Nevertheless, the ability to identify at-risk patients quickly could vastly improve treatment of COVID-19 and allow for effective distribution of scarce resources.
 
Thailand Medical News would like to add that diets rich in wheatflour, eggs, dairy products, soyabean and also cauliflower are rich in both Sphingosine and Acid Ceramidase (AC).
 
Also phytochemical extracts from the herbal plant Gentiana lutea have been found to help increase blood Acid Ceramidase (AC) levels and subsequently Sphingosine as well. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221824/
 
Gentiana lutea is also used in our therapeutic teas. https://www.thailandmedical.news/news/new-therapeutic-teas-
 
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