MUSC researchers screen for sugar modifications to assess immunity against COVID-19

Julia Lefler
June 30, 2020
Dr. Peggy Angel (left), Dr. Richard Drake (center), and Dr. Anand Mehta (right)
Dr. Peggy Angel (left), Dr. Richard Drake (center), and Dr. Anand Mehta (right) of the Department of Cell and Molecular Pharmacology and Experimental Therapeutics

The need for efficient methods of screening and testing for COVID-19 is at an all-time high as communities have begun to lift their stay-at-home restrictions, and case numbers have started to spike. A team of MUSC researchers is developing a way to test individuals rapidly for immunity against the disease. The researchers hope they will have this technology ready for use in MUSC Health clinics in time for the second wave of COVID-19.  

SARS-CoV-2, the virus that causes COVID-19, is covered in sugar molecules called glycans. These glycans can interact with the deep layer of glycans on our own cells and result in viral entry. 

MUSC researchers Peggi Angel, Ph.D., Richard Drake, Ph.D., and Anand Mehta, D.Phil., with the Department of Cell and Molecular Pharmacology and Experimental Therapeutics, study sugars attached to proteins. Together, they founded the company GlycoPath, with the goal of generating clinical methods to study changes in glycans associated with various diseases. 

“There are still a lot of things about this virus that we don’t know, like why it causes a dramatic disease in some while others remain asymptomatic. What we do know, though, is that all of these interactions in our bodies are mediated by glycans [sugar molecules].”

-- Dr. Richard Drake, Endowed Chair, Proteomics

Upon infection with a virus, such as SARS-CoV-2, the immune system produces proteins called antibodies that act like soldiers to fight off foreign invaders, such as a virus. These soldiers learn to recognize and kill specific viral particles to prevent infection from the virus in the future. 

It is also known that glycans attached to the antibodies help to dictate their actions against a disease. 

“There are still a lot of things about this virus that we don’t know, like why it causes a dramatic disease in some while others remain asymptomatic,” said Drake. “What we do know, though, is that all of these interactions in our bodies are mediated by glycans.”  

Using their expertise in the field of glycobiology, the team has developed a pilot test called the “glycotyper,” originally intended to screen for certain glycans associated with cancers but with wide application to other diseases. 

Dr. Richard Drake standing in front of the MALDI mass spectrometer. 
Dr. Richard Drake in front of the MALDI mass spectrometer.

This test can also be used to analyze and identify sugars on antibodies in the blood or saliva of an individual who has been infected by SARS-CoV-2.  

 “It will allow us to test patients who have been infected with SARS-CoV-2 and differentiate those who will develop a significant disease that forces them into an ICU unit or a milder disease that would only require isolation and some oxygen,” said Mehta. “It’s a broad technology that allows us to look at very specific proteins and get information out of it.” 

“We’re trying to develop a test that will reveal more information about the nature of the infection in an individual and how severe their disease will be.”

-- Dr. Anand Mehta, SmartState Endowed Chair in Proteomic Biomarkers

This technology will allow the team to analyze the antibodies, or soldiers, from a COVID-19 patient and determine how effective he or she will be at fighting off the virus. 

“We’re trying to develop a test that will reveal more information about the nature of the infection in an individual and how severe their disease will be,” remarked Mehta. “None of the current tests being used in the clinic reveal who will have severe disease with this virus and who will remain asymptomatic. Our goal is to fill in that gap in our knowledge with clinical accuracy.” 

Two types of tests are currently available for COVID-19. The antibody test reveals whether patients have been exposed to SARS-CoV-2. It cannot determine how recently they were exposed or whether they mounted an effective immune response. The nasal swab test determines whether the virus is present in the upper respiratory tract. Neither test, however, is able to determine whether a patient will have mild or severe disease or remain asymptomatic. 

Dr. Anand Mehta in his laboratory. 
Dr. Anand Mehta in his laboratory

The glycotyper assay could not only predict severity of disease, a clear advantage over any of the existing tests, but it could also test patients much more efficiently than anything currently used in the clinic. 

“Other assays being used in the clinic can take two to three days per sample,” said Drake. “The assay we are developing can be completed in a few hours with minimal amount of sample per patient.” 

The test’s efficiency could be crucial in controlling the spread of the disease in the community. Not only will this method allow more people to be tested, but it will quickly identify those who need to isolate themselves so that they do not continue to spread the virus in the community. 

This method is similar to an antibody test that looks for specific antibodies in the blood of a patient who has been infected by this disease. However, this MUSC-developed test has the advantage of being able to screen for many antibodies of interest that are spotted on a pre-coded, commercially available glass slide. A few microliters of serum or saliva from a patient are placed on the slide, and glycoproteins are captured by their corresponding antibodies on the slide. The captured glycoproteins are then imaged, using a special mass spectrometer that enables the investigators to visualize what sugars are present.  

“Importantly, we can add up to 100 samples on one slide, so this can be easily scaled up to screen many patients,” said Angel. 

“What’s exciting about this technology is that we started out developing this test for cancer. Now it’s applicable to COVID-19, which demonstrates that this unique technology developed here at MUSC can be useful for a broad range of diseases.”

-- Dr. Peggy Angel, Assistant Professor,
College of Medicine

In addition to predicting the severity of a patient’s disease, this method could be useful in the future to determine how effective certain vaccines or therapeutics are against the virus. 

“We can use this technology to evaluate a patient’s response to a vaccine or a drug to assess its efficacy against the disease,” said Drake. “That could help with future waves of this disease.” 

Partnering with Bruker, a company that develops scientific instruments, the group is attempting to speed up the transition from a laboratory-based assay to a clinical assay, with the hope that this technology will begin to be tested here at MUSC before a second wave of the pandemic hits. 

In addition to partnering with Bruker, the team is also teaming up with MUSC researchers Satish Nadig, M.D., D.Phil., medical director of the Center for Cellular Therapy, and Shikhar Mehrotra, Ph.D., co-scientific director of oncology and immunotherapy programs, to obtain samples from patients across South Carolina. 

“Using this technology, we are trying to help determine if there are differences in the type of immune response mounted against the virus that correlates to age, ethnicity or geographical location,” said Mehrotra. 

The efforts of researchers at MUSC highlight the importance of working together when it comes to taking on COVID-19. 

“What’s exciting about this technology is that we started out developing this test for cancer,” said Angel. “Now it’s applicable to COVID-19, which demonstrates that this unique technology developed here at MUSC can be useful for a broad range of diseases.” 

About the Author

Julia  Lefler

Keywords: COVID-19, Research