Respiratory syncytial virus in high-risk adults: A critical appraisal of therapeutic options and unmet needs

Respiratory syncytial virus (RSV) has traditionally been viewed as a causative agent of pediatric illness, yet accumulating evidence shows substantial morbidity and mortality among adults, particularly older individuals, those with cardiopulmonary comorbidities, and the immunocompromised. Although recent vaccine approvals for older adults represent major progress in prevention, effective therapeutic options for established infection remain limited. Herein we provide a critical analysis of existing and emerging antiviral and monoclonal antibody (mAb) therapies for the management of RSV infection in adults, highlighting current options and compounds in clinical development. At present, ribavirin remains the only antiviral recommended for treatment in adults, and no mAb has received regulatory authorization for prophylaxis or therapy in this population. Several development programs for direct-acting antivirals have been discontinued for reasons unrelated to safety or efficacy in adults, contributing to an ongoing treatment gap. Nevertheless, newer drug candidates, including ziresovir, EDP-938, and S-337395, have shown encouraging antiviral activity and acceptable safety in adult studies. By examining both the scientific evidence and the structural factors shaping the current landscape, we emphasize the need for sustained adult-focused clinical development to complement preventive vaccination. Addressing this therapeutic gap will be essential to reduce the burden of RSV disease in high-risk adult populations, particularly as the global population ages.