Washington: Children with specific immunodeficiency diseases have abnormalities in genes that regulate the body’s immune system against viral infections and are at higher risk of death from COVID-19, according to a new study. The study was published in the Journal of Allergy and Clinical Immunology. Most children infected with the SARS-CoV-2 coronavirus develop mild illness or show no symptoms at all. But for a small percentage, serious complications can develop.
“Mortality is much higher in children with primary immunodeficiency diseases infected with SARS-CoV-2. Our results indicate that basic immunological screening and genetic analysis should be performed in children with severe COVID-19 or multiinflammatory syndrome (MIS-C). Clinicians can then help these children with more precise therapies based on their genetic changes,” says Qiang Pan-Hammarstrom, professor in the Department of Biosciences and Nutrition, Karolinska Institutet, who led the study.
How the infection affects patients with primary immunodeficiency diseases, i.e. hereditary and congenital diseases of the immune system, is controversial. Even among these patients, some have severe COVID-19 while others have mild or no symptoms.
To investigate this more closely and to try to find genetic explanations for severe forms of COVID-19, researchers at Karolinska Institutet examined young patients with primary immunodeficiency diseases (also called congenital immunodeficiency disorders, IEI) who developed severe or critical SARS-CoV – 2 infection. Genetic and immunological analyzes were performed.
“Our results elucidate the molecular mechanism of these immune diseases, which opens up the possibility of developing a more targeted therapy. The insights gained from the study also allow us to develop better strategies to treat and prevent severe COVID-19 disease in these patients,” says Qiang Pan-Hammarstrom.
The study included 31 children aged five months to 19 years. All children had some type of primary immunodeficiency disease with no molecular diagnosis and had severe or critical COVID-19. Participants were recruited in Iran from August to September 2020. None of the children were vaccinated against COVID-19.
Eleven of the children, more than a third, died as a result of the infection. Five children, 16 percent, met criteria for multiinflammatory syndrome, MIS-C. Some children lacked antibodies against the coronavirus.
“This suggests that many children with this type of immune disease are unable to produce antiviral antibodies and therefore would not get the full benefit of vaccination,” says Hassan Abolhassani, assistant professor in the Department of Biosciences and Nutrition, Karolinska Institutet, and the study’s first author .
Genetic analyzes showed that more than 90 percent of the participants, 28 children, had mutations in genes that are important for our immune system and that could explain their immune deficiency. One important mechanism was mutations affecting proteins that regulate the immune system during viral infection, called interferons.
Analyzes of patients’ immune responses showed that children with MIS-C had different immunological profiles than children with primary immunodeficiency but without MIS-C.
The study also includes a literature review in which the researchers found reports of approximately 1,210 patients with primary immunodeficiency disease and COVID-19 worldwide. About 30 percent of them were children. The mortality rate among children with primary immunodeficiency disease and COVID-19 was more than eight percent, compared with about 0.01 percent for children in the general population.
The study is limited to severe cases of COVID-19 infected with the original strain of the virus and unvaccinated children. Further studies are needed to evaluate the importance of different virus variants and vaccines in this patient population.
The study was conducted within the research consortium ATAC, funded by the European Commission in response to the COVID-19 pandemic and coordinated by Karolinska Institutet. Cooperation with Uppsala University, Tehran Medical University (Iran), Iran Medical University, Ahvaz Jundishapur Medical University (Iran), North Khorasan Medical University (Iran), Howard Hughes Medical Institute (USA), Rockefeller University ( USA) and Necker Hospital for Sick Children (France) were also instrumental in conducting the study.
The study was also funded by the Swedish Research Council and the Knut and Alice Wallenberg Foundation.