Predisposition to viral infection of the fetus and neonate

Viral infection-related hospitalization and mortality rates are highest in human newborns and infants compared to older children and adults, suggesting age-specific vulnerability and a non-redundant role for the maternal immune system. However, there is immense interindividual variability of clinical outcomes following early-life exposure to nearly any given virus that cannot be fully explained by variation in maternal immune protection. Inborn errors of immunity underlying defective control of viral replication or insufficient immune regulation following a viral trigger are increasingly recognized as the molecular etiology of severe viral disease in children and adults. In parallel, auto-antibodies (auto-Abs) neutralizing type I interferons (IFNs) are emerging as universal determinants of viral disease. The role of inborn errors of antiviral immunity in the fetus, the newborn, and the infant is starting to emerge or can be inferred from the study of viral disease in older individuals. The investigation of the molecular mechanisms underlying early-life viral disease in individual patients is crucial to the development of effective prevention and treatment strategies. Novel studies addressing the role of inborn errors of antiviral immunity or auto-Abs neutralizing type I IFNs in early-life viral infections should take into account the specific aspects of the neonatal immune system and its complex interactions with the maternal immune system.