key: cord-0008378-elltaidc
authors: Lee, Nelson; Hui, David S C
title: Potential and challenges of serotherapy for severe influenza
date: 2017-07-22
journal: Lancet Respir Med
DOI: 10.1016/s2213-2600(17)30266-7
sha: d1437e9cb58174936f2bc00809f4d9334da1c14a
doc_id: 8378
cord_uid: elltaidc

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reports also described an absence of efficacy when serotherapy was given later in the disease course (SARScoronavirus >10 days; A/H1N1 pdm09 >5 days). 2 Available evidence suggests that viral replication is most active and viral load is at its peak during the earlier periods, which could have affected the therapeutic time window for antiviral agents (eg, ≤5 days for neuraminidase inhibitors, with highest benefits when given ≤2 days), in these severe infections. 3 Such observations and the futility of non-specific IVIG suggest that the predominant role of serotherapy could be neutralisation and inhibition of the invading virus, although other mechanisms such as immunomodulation might coexist. 2 Viral load reduction was not shown in Beigel and colleagues' main analysis, but sub-analysis of their data according to virus subtype and the respective virus neutralising antibody titre, and future data from the low (haemagglutination inhibition titre ≤1:10) versus high (haemagglutination inhibition titre ≥1:80) antibody concentration plasma trial (NCT02572817) might provide additional insight and help to define the actual effective titre or dose by bodyweight.

If efficacy can be established, it would be important to define the patient group that would benefit most from adjunctive serotherapy in addition to neuraminidase inhibitors, which is currently considered as the standard of care. Several prognostic indexes based on presenting clinical and laboratory parameters (eg, PaO 2 to FIO 2 ratio, Acute Physiology and Chronic Health Evaluation [APACHE] II, and metabolomics) have been proposed, and might assist risk stratification. 4 The magnitude of improvement in outcomes over neuraminidase inhibitor treatment alone, and its risk-to-benefit ratio will need to be further addressed because of several potential safety concerns 

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