Host Immunomodulatory Interventions in Severe Influenza

Area of Science:

• Influenza research
• Immunomodulatory therapies
• Critical care medicine

Background:

• Severe influenza lacks proven immunomodulatory treatments.
• WHO conditionally advises against several agents like corticosteroids and macrolides.
• High-dose corticosteroids may worsen outcomes, but low-dose warrants investigation.

Purpose of the Study:

• To review current evidence on immunomodulatory agents for severe influenza.
• To identify promising therapeutic strategies and areas for future research.
• To inform a multidisciplinary approach integrating antiviral and immunomodulatory treatments.

Main Methods:

• Systematic review of clinical trials and observational data.
• Analysis of immunomodulatory agents including corticosteroids, passive immunotherapy, and novel drugs.
• Evaluation of treatment combinations and their impact on severe influenza outcomes.

Main Results:

• Oseltamivir, clarithromycin, and naproxen combination showed improved outcomes in one RCT.
• Sirolimus with corticosteroids expedited ventilation liberation and reduced viral load in an RCT.
• Passive immunotherapy (convalescent plasma, IVIG) has not proven effective; hyperimmune options are suggested.
• Other agents like macrolides, nitazoxanide, and mycophenolic acid showed limited or concerning results.

Conclusions:

• Large-scale trials are necessary to validate promising findings for agents like sirolimus and combination therapies.
• Future research should focus on hyperimmune plasma, specific immunomodulators, and combination strategies.
• An integrated approach combining antivirals and immunomodulators is crucial for enhancing severe influenza patient outcomes.