IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study

Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 ( ) in COVID-19 patients. We show that is expressed in the respiratory tract of COVID-19 patients and elevated expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, like genes were highly upregulated in the blood samples of severely infected patients. These data suggest that prognostic biomarkers targeting the family of genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.