COVID-19 Outcomes Influenced by Antibody Response

A recent study conducted by investigators from the Ragon Institute of MGH, MIT and Harvard, in collaboration with the Massachusetts General Hospital Cystic Fibrosis Center, has identified specific types of antibodies which may drive different coronavirus disease 2019 (COVID-19) responses in adults and children. Data from the study was published in the journal Nature Medicine.

Treatment for the SARS-CoV-2 virus is difficult due to the various ways in which the disease presents itself. For example, the majority of children who contract the virus are asymptomatic or only experience mild disease. However, some children who contract COVID-19 are at a high risk for multisystem inflammatory syndrome in children (MIS-C). MIS-C is a rare and serious syndrome that can eventually lead to cardiac disease and ventricular failure.

Investigators behind the study employed a unique systems serology technology and carefully conducted a detailed comparison of immune responses in children and adults. The study included 17 children with MIS-C and 25 with mild disease, as well as 26 adults with severe disease and 34 adults with mild disease.

"We were expecting the children's immune responses to look drastically different from the adults', regardless of the severity of disease," Galit Alter, a core member of the Ragon Institute said. "But instead, we found that adults with mild COVID-19 and children with COVID-19 had remarkably similar immune responses. It was only the adults with severe COVID-19 whose immune responses looked different."

The investigators found 2 specific antibodies, one leading to severe disease in adults and another leading to MIS-C in children. In the children, they discovered high levels of IgG antibodies, which can cause inflammation in different organs and systems by activating macrophages. The high levels of IgG were found only in those children who developed MIS-C after contracting COVID-19.

In the adults, the investigators saw high levels of IgA antibodies, which interact with the immune cells called neutrophils and can cause them to release cytokines. Too many of these antibodies can cause an excess of cytokines, which may contribute to the cytokine storm in severe cases of the disease.

These findings are a first step in understanding the varying responses that COVID-19 causes in different populations. Knowing what drives these outcomes will help investigators to develop treatments that can prevent or modulate immune responses.