Viral hemorrhagic fevers - therapeutic trial advances and challenges

Abstract

IntroductionViral hemorrhagic fevers (VHFs) represent a group of severe diseases caused by RNA viruses with high fatality rates, posing significant global health threats. These diseases are prioritized by the World Health Organization due to their epidemic potential, geographical restrictions, and limited therapeutic options.Areas coveredThis review discusses the current state of therapeutic advancements, challenges in treatment, and post-exposure prophylaxis for various VHFs. Relevant literature on VHFs and therapeutic interventions was identified through searches of PubMed, Scopus, Web of Science, WHO and CDC databases, and ClinicalTrials.gov from database inception to November 2025. Key therapies like ribavirin for Crimean-Congo hemorrhagic fever and Lassa fever, along with monoclonal antibodies for Ebola and Marburg virus disease, have demonstrated clinical efficacy. However, gaps remain in effective antivirals and vaccines for many VHF pathogens.Expert opinionNotable challenges in therapeutic development include ethical concerns in randomized controlled trials, logistical barriers in endemic areas, and the evolving immune response in late-stage disease. The role of cytokine modulation and the growing potential of monoclonal antibodies offer new directions for treatment. Strengthening observational studies and expanding international collaboration are critical for improving patient outcomes and advancing therapeutic options for these deadly diseases.