According to a new study, children with certain immunodeficiency diseases have abnormalities in the genes that regulate the body’s immune system against viral infections and have a higher risk of dying from COVID-19.
The study was published in the Journal of Allergy and Clinical Immunology.
Most children infected with SARS-CoV-2 develop mild illness or no symptoms at all. But for a small percentage, serious complications may occur.
“The mortality rate is much higher among children with primary immunodeficiency diseases infected with SARS-CoV-2. Our results suggest that primary immunological screening and genetic analysis should be performed for children with severe COVID-19 or multiple inflammatory syndrome (MIS-C). Physicians will be They are then able to help these children with more precise treatments based on their genetic changes,” says Chiang Pan Hammarstrom, a professor in the Karolinska Institutet’s Department of Biological Sciences and Nutrition, who led the study.
How infection affects patients with primary immunodeficiency diseases, such as 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 try to find genetic explanations for severe forms of COVID-19, researchers from Karolinska Institutet studied young patients with primary immunodeficiency diseases (also called genetic errors of immunity, IEI) who had been infected with severe or severe SARS virus. -2 infection. Genetic and immunological analyzes were performed.
“Our results elucidate the molecular mechanism of these immune diseases, opening up the possibility of developing more targeted therapy. The knowledge gained from the study also allows us to develop better strategies for treating and preventing severe COVID-19 disease in these diseases,” says Chiang Pan Hammarstrom.
The study included 31 children aged between five months and 19 years. All of the children had some form of primary immunodeficiency without a molecular diagnosis and had severe or severe COVID-19. Participants were recruited from August to September 2020 in Iran. None of the children have been vaccinated against COVID-19.
Eleven of the children, more than a third, died of complications from the infection. Five children, 16 percent, met the criteria for multiple inflammatory syndrome, MIS-C. Some of the children lacked antibodies to the coronavirus.
“This suggests that many children with this type of immune disease cannot produce antiviral antibodies and therefore will not have the full benefit of vaccination,” says Hassan Abulhassani, assistant professor in the Department of Biological Sciences and Nutrition at Karolinska Institutet and first author of the study. .
Genetic analyzes showed that more than 90 percent of the participants, 28 children, had mutations in genes important for immune defense, and this could explain their immunodeficiency. An important mechanism was mutations that affect proteins that regulate the immune system during infection with the virus, known as interferon.
Analyzes of the patients’ immune responses showed that children with MIS-C had immune profiles that differed from those of children with primary immunodeficiency but without MIS-C.
The study also includes a literature review, where researchers globally found reports of about 1,210 patients with primary immunodeficiency disease and COVID-19. About 30 percent of them were children. The death rate among children with primary immunodeficiency virus and COVID-19 was more than eight percent, compared to about 0.01 percent among 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 assess the significance of viral variants and different vaccines in this group of patients.
The study was conducted within the ATAC research consortium, funded by the European Commission in response to the COVID-19 pandemic and coordinated by Karolinska Institutet.
Cooperation with Uppsala University, Tehran University of Medical Sciences (Iran), Iran University of Medical Sciences, Ahvaz Gundishapur University of Medical Sciences (Iran), North Khorasan University of Medical Sciences (Iran), Howard Hughes Medical Institute (USA), Rockefeller University (US USA) and Necker Hospital for Sick Children (France) were also critical to the implementation of the study.
The study was also funded by the Swedish Research Council and the Knut and Alice Wallenberg Foundation.
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