Abstract
BackgroundA range of immunomodulatory therapies have been proposed as adjuncts to conventional antivirals to suppress harmful inflammation during severe influenza infection. We conducted a systematic review to assess available data of the effect of adjunctive non‐corticosteroid immunomodulatory therapy and potential adverse effects.MethodWe searched MEDLINE, Embase, Web of Science and clinical trial databases for published and unpublished studies, and screened the references of included articles. We included RCTs, quasi‐RCTs and observational studies of virologically confirmed influenza infections in hospitalised patients. We did not restrict studies by language of publication, influenza type/subtype or age of participants. Where possible, we pooled estimates of effect using random‐effects meta‐analysis models.ResultsWe identified 11 eligible studies for inclusion: five studies (4 RCTs and 1 observational; 693 individuals) of passive immune therapy; four studies (3 RCTs and 1 observational; 1120 individuals) of macrolides and/or non‐steroidal anti‐inflammatory drugs (NSAIDs), one RCT of mTOR inhibitors (38 individuals), and one RCT of statin therapy (116 individuals). Meta‐analysis of RCTs of passive immune therapy indicated no significant reduction in mortality (OR 0.84, 0.37‐1.90), but better clinical outcomes at Day 7 (OR 1.42, 1.05‐1.92). There was a significant reduction in mortality associated with macrolides and/or NSAIDs (OR 0.28; 0.10‐0.77).ConclusionsPassive immune therapy is unlikely to offer substantial mortality benefit in treatment of severe seasonal influenza, but may improve clinical outcomes. The effect of other immunomodulatory agents is uncertain, but promising. There is a need for high‐quality RCTs with sufficient statistical power to address this evidence gap.
Highlights
Seasonal influenza is a common viral infection of the respiratory tract
The recent 2018 Infectious Diseases Society of America (IDSA) seasonal influenza guidelines do not recommend any immunomodulatory therapies as adjunctive treatments.[3]
This systematic review focuses on immunomodulatory agents other than corticosteroids for the treatment of severe influenza
Summary
Seasonal influenza is a common viral infection of the respiratory tract. It is estimated to cause more than a billion infections annually, with three to five million severe illnesses and 250 000-650 000 deaths.[1,2] The highest mortality rates have been reported in adults aged over 75 years, children younger than 5 years and residents of sub-Saharan Africa or South-East Asia. The recent 2018 Infectious Diseases Society of America (IDSA) seasonal influenza guidelines do not recommend any immunomodulatory therapies as adjunctive treatments.[3] This systematic review focuses on immunomodulatory agents other than corticosteroids for the treatment of severe influenza. Three systematic reviews of passive immune therapy (convalescent plasma/serum or intravenous immunoglobulin) for the adjunctive care of severe influenza were. This systematic review was commissioned by the World Health Organization (WHO) to inform the development of clinical practice guidelines for severe influenza. It aims to provide a comprehensive and up-to-date assessment of the available data investigating the clinical effectiveness and safety of non-corticosteroid immunomodulatory therapy adjunctive to conventional antiviral medication for the treatment of severe influenza
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