In addition to
neuraminidase inhibitors and other drugs that directly target viral replication, a number of adjunctive and
immunomodulatory therapies are currently under evaluation for the treatment of
influenza. These novel treatments, which focus either on pathophysiological aspects of influenza virus
infection or the neutralization of virus with
antibodies, are the subject of this review.
Cytokine dysregulation has been observed in patients with severe
influenza, such as
avian influenza A (H5N1) and pandemic 2009
influenza A (H1N1pdm09)
virus infections, but the role of
immunomodulatory therapy is unclear, due to lack of data from randomized controlled trials (RCTs). Convalescent plasma appears to be useful as an adjunctive
therapy for the treatment of H5N1 and H1N1pdm09
infections. Until lately, data interpretation was limited to case reports and studies of non-randomized design, but a recent RCT found that patients with severe
influenza A (H1N1pdm09) who were treated with hyperimmune
immunoglobulin from persons who had survived the same disease had a lower peak viral load and lower mortality than controls, providing treatment was begun within 5 days of symptom onset. The efficacy of agents with potential immunomodulating effects, including
intravenous immunoglobulin,
N-acetylcysteine, acute use of
statins,
macrolides,
peroxisome proliferator-activated receptors agonists,
celecoxib and
mesalazine, and the role of
plasmapheresis and
hemoperfusion as rescue
therapy, deserve more investigation and where feasible, studies by RCTs. Prospective observational studies have shown that systemic
corticosteroids increase morbidity (e.g.,
secondary infections) and mortality in H1N1pdm09
influenza. This article forms part of a symposium in
Antiviral Research on "Treatment of
influenza: targeting the virus or the host."