Viral Sepsis in Children

Gupta, Neha; Richter, Robert; Robert, Stephen; Kong, Michele

Viral pathogenesis in children also varies according to the degree of host immunocompetence. Generally, young infants have significantly reduced TLR expression, antigen-presenting cell activity, NK cell responsiveness, T-cell functionality, B-cell maturity, and complement concentration (70) . This immaturity of the developing immune system places young infants at significantly higher risk for severe disease from viruses that would typically cause minimal harm to older children and adults (e.g., HSV, HPeV, enteroviruses, CMV). Similarly, children with congenital or acquired immunodeficiencies are more susceptible to viral pathogens. Specific immunodeficiencies that place children at higher risk for viral sepsis include NK cell deficiency, interferon (IFN)-γ receptor deficiency, TLR-3 deficiency, nuclear factor-kappa B essential modulator deficiency, severe combined immunodeficiency, severe T-cell lymphopenia in DiGeorge syndrome, agammaglobulinemia, and hyperIgM syndrome (71). Severe RNA viral infections have also been observed in patients with loss-of-function mutation of the IFN induced with helicase C domain 1 (IFIH1) gene that encodes the RLR MDA5 (36, 37, 72) . Moreover, children receiving immunomodulatory or immunosuppressive therapies due to malignancy, transplantation, or autoimmune disease are more susceptible to viral infection or reactivation.