Inborn errors of immunity aggravate COVID-19 death risk

Children with pre-existing inborn errors of immunity (IEI) are at greater risk of death when infected with the SARS-CoV-2 virus, according to a new study.

The study included 31 children and youth (aged 0.5–19 years) with pre-existing inborn errors of immunity but had no definitive molecular diagnosis. All participants later contracted COVID-19 complications. Study endpoints included COVID-19 disease severity and clinical outcomes, as well as SARS-CoV-2-specific antibodies and other immune markers.

Overall, 90.3 percent (n=23) of participants ultimately received a potential genetic cause for their IEI, including mutations that could adversely affect the complement system, the inflammasome, interferon signaling, and B and T cell function. Fourteen patients were able to produce virus-specific antibodies.

During the follow-up, five patients died of COVID-19 complications, particularly infectious in nature, yielding a mortality rate of 35.4 percent. This represents a “3,000-fold higher mortality rate compared to the COVID-19 death rate in normal children,” which rests at around 0.01 percent, the researchers said. [Nature 2021;595:639]

Subsequent literature synthesis found that of the 381 children with IEI who had contracted COVID-19 to date, 23.6 percent developed severe disease and the mortality rate was at 8.7 percent.

“As this study was limited only to the severe cases affected with wild-type virus and without vaccination, further studies are needed to evaluate the impact of different variants of concerns and different types of vaccines on this specific group of patients,” the researchers said.

Nevertheless, “our overall findings emphasize the need for a paradigm change about SARS-CoV-2 infected children as severity and mortality are extremely high in paediatric patients with a history of IEI,” they added.