Searching for the genes involved in Long COVID in children

Fortunately, most children hardly have any symptoms during or after a COVID-19 infection. However, a small group develops a life-threatening inflammatory disease called multi-system inflammatory syndrome in children (MIS-C) after a COVID-19 infection. This disease causes high fever to develop and inflammations to suddenly occur throughout the entire body, for example in the heart and kidneys. Most children with these symptoms end up in intensive care. After a COVID-19 infection, there are also children that experience symptoms, which match those of Long COVID. MIS-C and Long COVID symptoms only come to light weeks after the COVID-19 infection, whereas the actual infection can pass fairly unnoticed. We examine why this group of children is susceptible to MIS-C or Long COVID.

In the case of MIS-C, the immune system seems to be deregulated. We think that in these children, changes occur in genes that are important for a proper functioning of the immune system. Our question was whether these children might have a congenital immune disorder. International research has already provided indications for this. It might be that the immune system does not function properly in the case of Long COVID too. However, there is not enough knowledge about this and we therefore received ZonMw funding to further investigate this problem.

Children with MIS-C can be treated with immunosuppressive drugs. They end up in intensive care due to an extremely low blood pressure caused by an inflamed heart muscle. As a result of this, the heart can no longer pump blood out of the heart powerfully enough. Also, the immune system produces a lot of inflammatory proteins, the so-called cytokines. We can stop this cytokine storm with the help of immunosuppressants, which make this inflammatory response disappear and cause the blood pressure to increase again. Fortunately, MIS-C can be treated well in children. The situation is not yet clear enough to provide a proper treatment for Long COVID because we currently possess too little knowledge about what happens in the body of a child with Long COVID. Various theories about the underlying mechanisms of Long COVID exist but we still lack an unequivocal understanding of this. It might differ per person, and differences between children and adults with Long COVID could exist. With our research into the immune system of children with Long COVID, we hope to collect more information about that. And that will hopefully provide starting points that provide prospects for a treatment.

For this GRIP study, we recruited children with MIS-C from the COPP study, and children with Long COVID from another ongoing study of the Emma Children’s Hospital in Amsterdam. We collect saliva from a hundred children who have had MIS-C and a hundred children with Long COVID. We compare their DNA with the DNA of the control group: children who have had COVID-19, but did not develop MIS-C or Long COVID. There is a list of genes that are involved in immune disorders. Do children with MIS-C and Long COVID more often show changes in these genes than children from the control group?

If it becomes clear which genes may be involved in the immune disorder, then we will know more about the background of the symptoms. We can subsequently begin to search for a targeted treatment for the group of children who continue to experience serious symptoms following a COVID-19 infection. At present, we only use general immunosuppressors, but once it becomes known which genes are involved, we can target the symptoms more specifically.