Children with primary immunodeficiency may be at higher risk of serious complications from Covid-19

WASHINGTON: According to a new study, children with specific immunodeficiency diseases have abnormalities in genes that regulate the body’s immune system against viral infections and have a higher risk of death from COVID-19. 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. 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 examination and genetic analysis should be performed in children with severe COVID-19 or multi-inflammatory syndrome (MIS-C). Clinicians will then be able to help these children with more precise therapies based on their genetic changes,” says Qiang Pan-Hammarstrom, a professor in the Department of Biosciences and Nutrition at Karolinska Institutet, who led the study.

How the infection affects patients with primary immunodeficiency diseases, ie hereditary and congenital diseases of the immune system, is controversial.

Even among these patients, some are suffering from 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 at Karolinska Institutet studied young patients with primary immunodeficiency diseases (also called inborn errors of immunity, IEIs). who have developed severe or critical SARS-CoV. -2 infections.

Genetic and immunological analyzes were carried out. “Our results shed light on the molecular mechanism of these immune diseases, which opens up the possibility of developing a more targeted therapy.

The knowledge gained from the study also allows us to develop better strategies for the treatment and prevention of severe COVID-19 disease in these patients,” says Qiang Pan-Hammarstrom.

The study included 31 children aged five months to 19 years. All of the children had some type of primary immunodeficiency disease without molecular diagnosis and had severe or critical 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%, met criteria for multi-inflammatory syndrome, MIS-C. Some of the children lacked antibodies against the coronavirus.

“This suggests that many children with this type of immune disease cannot produce antiviral antibodies and therefore would not fully benefit from vaccination,” says Hassan Abolhassani, assistant professor in the Department of Biosciences and Nutrition, Karolinska Institutet. , and first author of the study. .

Genetic analyzes showed that more than 90% of the participants, 28 children, had mutations in genes important for our immune defense, and which could explain their immunodeficiency.

One important mechanism was mutations that affect proteins that regulate the immune system during viral infection, known as interferons.

Analyzes of patient 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, where the researchers found reports of approximately 1,210 patients with primary immunodeficiency and COVID-19 worldwide.

About 30% of them were children. The mortality rate among children with primary immunodeficiency and COVID-19 was over 8%, compared to about 0.01% 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 importance of different virus variants and 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 the Karolinska Institute.

Collaboration with Uppsala University, Tehran University of Medical Sciences (Iran), Iran University of Medical Sciences, Ahvaz Jundishapur University of Medical Sciences (Iran), University of Sciences Medical Centers of North Khorasan (Iran), the Howard Hughes Medical Institute (USA), Rockefeller University (USA) and Necker Hospital for Sick Children (France) also played a crucial role in 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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