Scientists in Dubai have identified genetic factors that may put certain children at greater risk of having a potentially fatal reaction when infected with Covid-19.
Researchers used data from dozens of youngsters in Dubai and Jordan to determine what genetic variants increased the likelihood of them developing multisystem inflammatory syndrome in children (MIS-C).
Previous studies have highlighted the role genes play in causing MIS-C, but this new research is unusual in that it included many Arab children, who are often not included in large numbers in studies of this kind.
The work was led by scientists at Mohammed Bin Rashid University of Medicine and Health Sciences and Al Jalila Children’s Hospital, both in Dubai, and published in JAMA Network Open.
“This is an important study not only because the findings show comprehensive genetic profiling of children with MIS-C, which is essential to characterise the genetic contribution to the disease, but also because patients of an Arab background have long been under-represented in genetic studies,” Dr Walid Abuhammour, head of the paediatric infectious diseases department at Al Jalila Children’s Specialty Hospital, and study investigator, said.
Issues with immunity regulation
The study involved analysing the genes, clinical symptoms and other factors of 45 Arab and Asian children who developed MIS-C, and comparing them to 25 children who also had Covid-19 but did not develop MIS-C.
The children were treated at Al Jalila Children’s Specialty Hospital and the Jordan University Hospital between September 2020 and August 2021.
MIS-C involves a type of over-reaction of the immune system, known as a cytokine storm, that can affect multiple organs and result in death. The cytokine storm has also been associated with deaths from Covid-19 in adults.
Among the other institutions to have researched MIS-C is Boston Children’s Hospital, which released a study in September that identified genetic risk factors that all pointed to, the hospital said, “underlying problems with immune regulation”.
Extreme reaction to infection
These variants caused the children to have what was described as an exaggerated response to viral infections, something that before the coronavirus emerged actually helped these individuals fight off infections. Particular chemical messengers in the body that stimulate the immune system were blamed for the over-reaction associated with MIS-C, as they could cause inflammation if released at the wrong time.
Like the Boston study last year, and others, the new research found that children who developed MIS-C were more likely to have particular rare genetic variants linked to the immune system.
“Although clinical presentations and laboratory markers in this cohort were consistent with recently described MIS-C cohorts elsewhere, our analysis revealed significant enrichment of rare, likely deleterious [harmful] [genetic] variants,” the study said.
These variants affect particular biochemical processes, the paper stated, that “overlap with the currently characterised immunologic profile in patients with MIS-C”.
The onset of the disease and resistance to treatment were also associated with genetic factors identified by the scientists.
More studies needed
“The results of this research suggest that rare genetic factors play a role in MIS-C disease and highlight immune-related pathways which might become targets for intervention,” Dr Ahmad Abou Tayoun, director of Al Jalila Children's Genomics Centre and associate professor of genetics at MBRU, said.
“Hopefully, this will now prompt additional studies to functionally characterise some of the identified genes, and to expand genomic sequencing to more diverse populations to fully characterise the genetic landscape of this new disease entity.”
The research was funded by the Al Jalila Foundation, which was founded by Sheikh Mohammed bin Rashid, Vice President and Ruler of Dubai.
As well as researchers at MBRU and Al Jalila Children’s Hospital, the study involved scientists at Dubai Health Authority, the University of Jordan and The Specialty Hospital in Amman.
