Progression of whole blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in patients with severe influenza

Transcriptional profiles and host response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole blood mRNA signatures, local and systemic immune mediator concentrations in 131 adults hospitalised with influenza from which extensive clinical and investigational data were obtained by the MOSAIC consortium. Signatures reflecting interferon-related antiviral pathways were common up to day 4 of symptoms in cases not requiring mechanical ventilatory support; in those needing mechanical ventilation an inflammatory, activated neutrophil and cell stress/death (‘bacterial’) pattern was seen, even early in disease. Identifiable bacterial co-infection was not necessary for this ‘bacterial’ signature but could enhance its development, while attenuating the early ‘viral’ signature. Our findings emphasise the importance of timing and severity in the interpretation of host responses to acute viral infection, and identify specific patterns of immune activation that may enable the development of novel diagnostic and therapeutic tools for severe influenza.