Children With Primary Immunodeficiency Disease May Have Higher Mortality from COVID-19

In a recent study, researchers observed that more than a third of children with a primary immunodeficiency disorder died from COVID-19.

Children with certain immunodeficiency diseases have a higher mortality rate from COVID-19, suggests a new study by Karolinska Institutet published in Journal of Allergy and Clinical Immunology.

Most children infected with COVID-19 are asymptomatic or have mild symptoms, but those with certain immunodeficiency diseases — also called inborn errors of immunity (IEI) — may have mutated genes that compromise the immune system, preventing it from protecting itself against infection. This can lead to serious or fatal complications.

“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,” said study leader Qiang Pan-Hammarström, professor in the Department of Biosciences and Nutrition, Karolinska Institutet, in a press release.

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In children with primary immunodeficiency disorders (examples include hereditary and congenital immune system disorders), certain individuals will have mild or no symptoms after contracting COVID-19, while others will have severe symptoms. According to the authors of the current study, it is controversial why the spectrum of symptoms differs so much.

Researchers at Karolinska Institutet wanted to find out whether genetics play a role in the severity of some COVID-19 cases in children with primary immunodeficiency diseases. Between August 2020 and September 2020, researchers in Iran identified 31 unvaccinated children who had the same primary immunodeficiency disease. Participants, aged 5 months to 19 years, had severe or critical COVID-19 infection.

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After conducting genetic and immunological analyses, the researchers determined that 11 children died from SARS-CoV-2 complications. Among the participants, 5 (16%) children were diagnosed with MIS-C.

Research suggests that patients with MIS-C differ from those without MIS-C because they cannot produce their own antiviral antibodies. Consequently, they “would not have the full benefit of vaccination,” said lead author Hassan Abolhassani, an assistant professor at the Karolinska Institute’s Department of Life Sciences and Nutrition, in the press release.

In addition, the genetic analyzes showed that more than 90% of children with primary immunodeficiency diseases had a mutation affecting proteins (interferons) that regulate the immune system during viral infection. These mutated genes could explain why their immune defenses aren’t working properly.

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Researchers performed an additional literature search of global reports examining this population. The team identified the mortality rate from COVID-19 in children with an IEI as 8%.

The study was limited to researching patients with severe COVID-19 cases, those infected with the original strain, and unvaccinated children.

“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 for the treatment and prevention of severe COVID-19 disease in these patients,” said Pan-Hammarström in the press release.


Karolinska Institute. Higher risk of serious COVID-19 complications in children with primary immunodeficiency. EurekAlert! September 16, 2022. Accessed September 19, 2022.

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