The use of hyperimmune serum for severe influenza infections

Background and Purpose: Although use of hyperimmune serum to treat patients with severe influenza infection, infections resistant to antiviral drugs, or as an interim therapy during a pandemic is frequently proposed, there have been no randomized case-control trials to investigate its efficacy. Reports of the use of hyperimmune serum in human influenza infection are sporadic and studies in animal models are limited. Methods: Ferrets exposed to an otherwise lethal dose of highly pathogenic avian influenza H5N1 were used as a model of severe human disease. Hyperimmune serum was administered 24 hrs before virus exposure, during early fever, or at the onset of initial clinical signs of influenza (lethargy, lack of appetite) to reflect clinically relevant intervention points. Animals were monitored for 14 days after challenge and assessed for local and constitutional signs of influenza as measured by survival, weight loss, activity scores, viral shedding, and seroconversion. Results: All animals administered hyperimmune serum homologous to the challenge virus before challenge survived the infection with no significant morbidity. The majority of animals receiving hyperimmune serum after virus exposure and during early fever survived the period of observation but showed significant morbidity and prolonged convalescence. The majority of animals that received serum later in the disease course died of acute infection. Conclusion: In highly pathogenic systemic influenza infections, the window for successful intervention by administration of hyperimmune serum may be narrow. (Crit Care Med 2012; 40:973-975)