Researchers continue to puzzle over why some patients infected with SARS-CoV-2, the virus that causes COVID-19, remain asymptomatic while others develop severe disease symptoms. This is a question that has resurfaced as the Delta variant spreads across the country.

Researchers at the Medical University of South Carolina (MUSC) discovered a specific and sensitive biomarker in blood samples that accurately predicts which patients will develop COVID-19 symptoms in a new retrospective study.

Their findings, which were published in Scientific Reports, indicate that low levels of a specific lipid, sphingosine, are associated with the development of COVID-19 symptoms. On the other hand, elevated levels of sphingosine, as well as the enzyme responsible for its synthesis, acid ceramidase (AC), are associated with asymptomatic infections.

Several waves of SARS-CoV-2 infections in the United States over the last 16 months have resulted in more than 35 million cases and nearly 630,000 deaths. Despite the development of numerous safe and effective vaccines, we are currently facing a new wave of infections.

COVID-19 mortality is thought to be caused by an excessive immune response to the virus in the lungs of infected patients, resulting in severe respiratory distress. However, symptoms vary considerably, and scientists and clinicians are baffled as to why some patients develop severe symptoms while remaining asymptomatic.

It is well established that sphingolipids, a class of molecules critical for the integrity of the cell membrane and cell-cell communication, can regulate inflammation and the immune system in response to a variety of infections. The Ogretmen laboratory has decades of experience analysing the production and processing of a variety of lipids, including sphingolipids, using a technique known as lipidomics.

The Ogretmen lab used this expertise to conduct an unbiased analysis of COVID-19 patient serum samples from the MUSC COVID-19 Biorepository in order to detect changes in sphingolipid levels.

The findings were startling.

The researchers discovered a slight increase in serum sphingosine levels—and only sphingosine—in asymptomatic patients who tested positive for a SARS-CoV-2 antibody. Sphingosine levels were found to be 15-fold lower in patients who developed COVID-19 symptoms. On the other hand, nearly 75% of asymptomatic patients had elevated AC levels, whereas the majority of symptomatic patients did not have detectable AC. The presence of serum AC is associated with increased sphingosine levels.

Using blood levels of sphingosine, there is a 99 percent probability of correctly predicting which patients who tested positive for SARS-CoV-2 antibodies will develop disease symptoms versus those who will remain asymptomatic.

There are still several questions remaining. What effect does vaccination have on sphingosine levels? How do sphingosine levels change as more variants are introduced?

Nonetheless, the ability to rapidly identify at-risk patients could significantly improve COVID-19 treatment and allow for more efficient distribution of scarce resources.