Higher risk of serious complications from COVID-19 in immunocompromised children

Children with certain immunodeficiency diseases carry mutations in genes that regulate the body’s immune system against viral infections and have a higher death rate from COVID-19. This is stated in a study by researchers of the Karolinska Institute, published in Journal of Allergy and Clinical Immunology.

The majority children those infected with the SARS-CoV-2 coronavirus develop mild disease or no symptoms at all. But a small percentage may develop serious complications.

“Mortality is much higher among children with primary immunodeficiency diseases infected with SARS-CoV-2. Our results show that basic immunological examination and genetic analysis should be performed in children with severe COVID-19 or polyinflammatory syndrome (MIS-C). Clinicians will then be able to help these children with more precise therapies based on them genetic changes” says Tien Pan-Hammarström, a professor in the Department of Biological Sciences and Nutrition at Karolinska Institutet, who led the study.

How the infection affects patients with primary immunodeficiency diseases (that is, inherited and congenital diseases of the immune system) is controversial. Even among these patients, some suffer from a severe form of COVID-19, while others experience mild or no symptoms.

To examine this more closely and try to find genetic explanations for severe forms of COVID-19, researchers from the Karolinska Institute studied small patients with primary immunodeficiency diseases (also called congenital immune disorders, IEI) who have developed severe or critical SARS-CoV-2 infection. Genetic and immunological analyzes were carried out.

The possibility of more targeted therapy

“Our results clarify the molecular mechanism of these immune diseases, which opens up the possibility of developing more targeted therapies. 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 Tien Pan-Hammarström .

31 children between the ages of five months and 19 years took part in the study. All children had some type of primary immunodeficiency without molecular diagnosis and suffered from severe or critical form of COVID-19. Participants were recruited from August to September 2020 in Iran. None of the children had been vaccinated against COVID-19.

Eleven children, more than a third, died from complications of the infection. Five children, 16%, met criteria for polyinflammatory syndrome, MIS-C. Some 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 fully benefit from vaccination,” says Hassan Abolhassani, associate professor of biological sciences and nutrition at Karolinska Institutet and first author of the study. .

Mutations of immune genes

Genetic analysis showed that more than 90% of the participants, 28 children, had mutations in genes that are important for our immune defenses, and this could explain their immunodeficiency. An important mechanism was mutations that affect proteins that regulate the immune system during viral infection, known as interferons.

Analysis of patients’ immune responses showed that children with MIS-C had immunological profiles different from those of children with primary immunodeficiency but without MIS-C.

The study also includes a literature review in which researchers worldwide found reports of approximately 1,210 patients with primary immunodeficiency and COVID-19. About 30% of them were children. Mortality rate of children from primary immunodeficiency disease and COVID-19 was more than 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 for this patient population.