How seriously a person suffers from COVID-19 has a lot to do with the body’s immune response to the SARS-CoV-2 virus and the infection it causes. Our immune system adapts antibodies to fight infections, so they are often used as an indicator to determine what type of illness we are facing or how likely it is to make us sick.
By taking a close look at one of the antibodies produced to fight COVID-19, researchers at Drexel University School of Medicine have discovered a trait that could be used to predict disease severity.
The discovery, reported recently in the journal Natural communicationsis linked to the presence of sugary structures, called glycans, which modify antibodies and affect their functioning.
Early research on COVID-19 focused on this modification, called glycosylation, as it occurred in long-lasting immunoglobulin G antibodies. The Drexel team’s discovery came from the study of an antibody produced earlier in the immune response, called immunoglobulin M (IgM).
“IgM plays a major role in how the immune system responds to pathogens like bacteria and viruses,” said Mary Ann Comunale, EdD, co-senior author of the research. “No one was interested in IgM glycans, so we made them the target of this work.” Comunale is an associate professor and glycobiologist at the Faculty of Medicine with more than two decades of experience in biomarker research focused on glycobiology.
The Drexel research group, led by MD/Ph.D. candidate Ben Haslund-Gourley, a student in the Comunale lab at Drexel’s College of Medicine, found that changes in the structures of glycans attached to IgM were associated with the severity of a patient’s COVID-19 infection — and these Changes in glycans can influence how the antibodies fight infection.
“What this paper tells us is that the immune system modifies IgM glycans, particularly in severe disease,” said co-senior author Elias El Haddad Ph.D., professor of microbiology and d. immunology at the Faculty of Medicine. “Although there is no rapid test to examine these glycans in hospitalized patients, these results can serve as a starting point for understanding the immune system response.”
Blood samples used in the study were from hospitalized COVID-19 patients participating in the National Institute of Allergy and Infectious Diseases’ Drexel Cohort “Evaluation of Immunophenotyping in a COVID-19 Cohort Study” ( IMPACC), of which El Haddad and co-study author and College of Medicine dean Charles Cairns, MD, are principal investigators. The researchers kept an eye on the patients, following the first 28 days of their illness.
“Once IgM binds to its target, it activates a cascade of proteins, called complements, that attack cell walls,” El Haddad explained. “While this activity can help fight infections, overactivation of complement can lead to organ failure.”
Severe COVID-19 infections have higher complement activity, a mechanism the body uses to fight pathogens. The Drexel team’s research suggests that glycans present on IgM could be partly responsible for this overactivation during severe illness.
“These results suggest that identification of IgM glycans could identify patients at risk of severe disease at an early stage of infection and help guide management,” Cairns said.
“Glycosylation of an antibody is essential when developing therapeutic products,” Comunale said. “Antibodies can have pro- or anti-inflammatory effects depending on the glycans present. Glycoengineering is a way to fine-tune an antibody to kill a pathogen more effectively and ensure that you don’t cause an increased response inflammatory disease of the patient. Therefore, these results inform the development of immunotherapy strategies for viral diseases.
The authors hope that this study of 22 patients will lead to larger studies of patients that will verify these findings, as well as future research looking at IgM and IgG in patients after they are discharged from the hospital to see if these glycans may help predict symptoms of long COVID.
“The collaboration began when Ben, a student in my lab, heard about the IMPACC study from his colleague Kyra Woloszczuk, a student in the Drexel lab of PhD Elias El Haddad, bringing together experts in glycobiology and immunology,” Comunale says . “The results of this work highlight two key points necessary for translational research: the importance of collaboration and the patient’s willingness to engage with scientists.”
More information:
Benjamin S. Haslund-Gourley et al, IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition, Natural communications (2024). DOI: 10.1038/s41467-023-44211-0
Provided by Drexel University
Quote: Researchers find possible predictor of COVID-19 severity (February 21, 2024) retrieved February 21, 2024 from
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