Blood Test for Specific and Sensitive Biomarker Can Predict Which Patients Will Develop COVID-19 Symptoms

The results of the study by researchers at Medical University of South Carolina (Charleston, SC, USA) 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.

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. 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 researchers undertook an unbiased analysis of COVID-19 patient serum samples from the MUSC COVID-19 Biorepository to look for changes in sphingolipid levels. The results were striking. In asymptomatic patients who tested positive for a SARS-CoV-2 antibody, the researchers 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.

Overall, 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. 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. 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.

“Can this be an alternative way to predict which patients are the most vulnerable to severe disease?” asked Besim Ogretmen, Ph.D., director of the Lipidomics Shared Resource at Hollings Cancer Center and leader of the Hollings Developmental Cancer Therapeutics Research Program.. “If we can separate asymptomatic patients from symptomatic patients, we can use limited remedies and resources for patients who are more vulnerable.”

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Medical University of South Carolina