“One of the major unanswered questions about MIS-C is how, immunologically, the disease evolves from the initial infectious episode to the final, immune-mediated assault,” says Gorelik. “One way to study this could be to identify what is unique about the inflammatory/immunologic response in MIS-C.”
Although other studies have looked at the immune and inflammatory response of MIS-C patients, most have compared patients with healthy controls after starting treatment. “To us, comparisons to healthy controls would not differentiate the basic inflammatory response to infection from the unique features of MIS-C, and, of course, treatment would muddy the waters,” says Gorelik.
Gorelik and Winchester’s team compared 8 MIS-C patients with 14 patients with other febrile infections and looked at the sequence of immune cells and blood samples taken during the first visit to the emergency department before treatment began.
Differences in Immune Cells
There may be clues as to what causes MIS-C in different immune cells found in MIS-C patients compared with other patients.
“Only some cells were activated, which suggests that these cells are mistakenly directing the immune system to attack blood vessels in the body that had been damaged by the virus,” says Winchester. “These cells are drawn to the blood vessels because of the presence of the virus, but they appear to misidentify the culprit when they alert the rest of the immune system.”
MIS-C also appears to drive patients’ natural killer cells Β another immune cell type Β to exhaustion. “They get to the point where they are no longer able to carry out their function properly,” Winchester says. “This is seen in some other inflammatory diseases and may offer a clue to treatment similar to those diseases.”
Faster Diagnosis?
Another finding may give physicians an easier way to diagnose MIS-C, which is difficult to distinguish from other syndromes.
It was also noted that interleukin-27 acts as an inflammatory molecule, which was very highly upregulated in patients with MIS-C but not in other febrile children.
“This cytokine is poorly understood but has been associated with increased mortality in patients with serious blood infection or sepsis,” Gorelik says.
“If validated, these findings may allow researchers to run a simple, easily available test to readily confirm MIS-C in patients when they are in the emergency department.”
Similarities with Other Major Disease in Adults
Columbia researchers say MIS-C and adult COVID-19 infections may be more similar than currently believed. “We noticed that several of our findings have also been reported in studies of adult patients with severe, late-stage COVID-19 infection,” Gorelik says.
“Perhaps Β and this is highly speculative Β what is unique to children is the ability to handle the initial viral infection more efficiently, and then a month or so later they develop MIS-C. In contrast, adults are not able to suppress the initial viral infection. And then secondarily, in severe cases, a serious MIS-C-like immune response develops. In both adults and children, however, this second phase immune signature appears quite similar.”
Further Information
The close collaborations with the pediatric and emergency medicine departments at Columbia University and co-authors Peter Dayan, MD, professor of pediatrics (in emergency medicine), and Tamar Lubell, MD, assistant professor of pediatrics (in emergency medicine) were also noted.
All contributors were Janice J. Huang (Columbia), Samantha B. Gaines (Columbia), Mateo L. Amezcua (Columbia), Tamar R. Lubell (Columbia), Peter S. Dayan (Columbia), Marissa Dale (Columbia), Alexis D. Boneparth (Columbia), Mark D. Hicar (University at Buffalo Medical Center), Robert Winchester (Columbia), and Mark Gorelik (Columbia).
The research was supported by grants from the National Institutes of Health (K08 HL155033 25), the U.S. Public Health Service, and the American Heart Association.
Source: Medindia
