Viral Sepsis in Children

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

For RSV infection, management is currently limited to passive immunization for at-risk infants. Palivizumab, an RSV-specific monoclonal antibody, is Food and Drug Administration (FDA) approved for the prevention of infection in high-risk infants during RSV season. The American Academy of Pediatrics has issued more clear recommendations for palivizumab use, stating that it should be administered as a monthly injection during RSV season in children born less than 29 weeks, 0 days gestation and are less than 12 months of age or in children with congenital heart disease, chronic lung disease (132) . Studies have shown variable efficacy of palivizumab, with reduction in RSV hospitalization rate by approximately 60% (133) . Currently, aerosolized ribavirin is the only FDA-approved treatment available for the management of RSV infection, though its use remains controversial (134) . To date, RSV vaccines and antiviral therapies remain an active area of investigation (135) . A randomized, controlled trial performed in adult patients with RSV infection compared the RSV entry inhibitor GS-5806 to placebo and demonstrated a decrease in both viral load and the clinical severity of infection in patients treated with GS-5806 (136) . Similar fusion inhibitors such as ALX-0171 (137), JNJ-2408068 (138) , , and VP14637 (138) demonstrate efficacy in vitro, and ALX-0171 is undergoing a phase II clinical trial in infants hospitalized for RSV (clinicaltrials.gov registration no. NCT02979431). The use of ALS-008176, an RSV polymerase inhibitor, has similarly been shown to reduce viral load, rapidly clear RSV, and improve the severity of disease in adults with RSV infection (140) . ALN-RSV01 is a lipidbased nanoparticulate system, containing small-interfering RNA (siRNA] that demonstrates promising antiviral effects against RSV in lung transplant patients (141) by targeting the mRNA of the RSV nucleocapsid protein, thereby limiting viral replication (142) . However, until these novel treatments have undergone appropriate clinical trials, the pediatric medical community must continue to wait for effective RSV antiviral therapy.