COVID-19, the source of the present pandemic, could also be caused by one virus, but it's a spread of presentations that make treatment difficult. Children, for instance, almost exclusively experience mild or asymptomatic COVID-19, while adults can develop severe or maybe fatal COVID-19.
But children who contract COVID-19 are in danger of a rare but serious syndrome called multisystem inflammatory syndrome in children (MIS-C). Severe cases of MIS-C can cause cardiac disease and ventricular failure and need hospitalization and intense medical support.
Researchers Galit Alter, Ph.D., a core member of the Ragon Institute of MGH, MIT and Harvard, and Lael Yonker, MD, director of the Massachusetts General Hospital CF Center, are working to know why COVID-19 can cause such distinctly different outcomes in several populations.
In a study recently published in Nature Medicine, they and their team identified specific sorts of antibodies which will be driving these different responses, including one specific to severe disease in adults and another specific to MIS-C in children.
"We noticed children who developed MIS-C after COVID disease or exposure had high levels of a selected sort of antibody called IgG," says Yonker. "Normally, IgG acts to regulate an infection, but with MIS-C, the IgG is triggering activation of immune cells, which can be driving the severe illness seen in MIS-C."
Specifically, explains Yonker, IgG antibodies interact with cells called macrophages, which live throughout the body's tissues. If there are too many IgG bodies activating these macrophages, this might cause inflammation in many various organs and systems, which is seen in MIS-C. These high levels of IgG antibodies were only found in children who developed MIS-C after contracting or being exposed to COVID-19.
Yonker, a pediatric pulmonologist at MGH and professor at Harvard school of medicine (HMS), runs a biorepository that collects samples from pediatric CF patients. When the pandemic hit, she began to gather samples from children with mild cases of COVID-19.
When Yonker and other pediatricians began seeing children hospitalized with what's now called MIS-C, which usually onsets three to 6 weeks after developing COVID-19, she quickly began collecting those samples too. She wanted to know how a light case of COVID-19 could lead to severe MIS-C weeks after recovery.
Seeking an in-depth understanding of the immune reaction, Yonker teamed up with Alter, who is additionally a professor at HMS and an immunologist within the Department of Infectious Diseases at MGH. Alter's a team used her unique "systems serology" technology to carefully perform an in-depth comparison of the immune responses in children--17 with MIS-C and 25 with mild COVID-19--to the responses of 26 adults with severe disease and 34 adults with mild disease.
"We were expecting the children's immune responses to seem drastically different from the adults', no matter the severity of the disease," says Alter. "But instead, we found that adults with mild COVID-19 and youngsters with COVID-19 had remarkably similar immune responses. it had been only the adults with severe COVID-19 whose immune responses looked different."
For adults with severe COVID-19, Alter explains, they saw increased levels of IgA antibodies, which interact with a kind of immune cell called neutrophils and cause the neutrophils to release cytokines.
If there are too many IgA antibodies, the neutrophils could also be pushed to release too many cytokines, which could contribute to a cytokine storm, one among the symptoms of severe COVID-19.
In both cases, the study shows, it's going to be a high level of a selected sort of antibody causing the disease severity.
In MIS-C, high levels of IgG antibodies could also be activating macrophages, which may drive inflammation in organs throughout the body. In adults with severe COVID-19, high levels of IgA antibodies might be driving neutrophils to release too many cytokines, with the potential of causing a cytokine storm."
Identifying the immune mechanisms of multiple, distinct responses to an equivalent virus is that the initiative to understanding why it mounts different responses in divergent populations.
Discovering how the immune system's response shapes the disease and its outcome in both children and adults can help researchers develop treatments that will prevent or modulate the immune reaction, keeping its protective functions but lessening the unintentional, yet harmful, ones.
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