Author: Shojaei, Maryam ; Shamshirian, Amir ; Monkman, James ; Grice, Laura ; Tran, Minh ; Tan, Chin Wee ; Rossi, Gustavo Rodrigues ; McCulloch, Timothy R. ; Nalos, Marek ; Chew, Keng Yih ; Zhu, Yanshan ; Xia, Yao ; Wells, Timothy J. ; Senegaglia, Alexandra Cristina ; Rebelatto, Carmen Lucia Kuniyoshi ; Franck, Claudio Luciano ; dos Santos, Anna Flavia Ribeiro ; de Noronha, Lucia ; Motamen, Sepideh ; Valadan, Reza ; Amjadi, Omolbanin ; Gogna, Rajan ; Madan, Esha ; Alizadeh-Navaei, Reza ; Lamperti, Liliana ; Zuniga, Felipe ; Nova-Lamperti, Estefania ; Labarca, Gonzalo ; Knippenberg, Ben ; Herwanto, Velma ; Wang, Ya ; Phu, Amy ; Chew, Tracy ; Kwan, Timothy ; Kim, Karan ; Teoh, Sally ; Pelaia, Tiana M. ; Kuan, Win Sen ; Jee, Yvette ; Iredell, Jon ; O'Byrne, Ken ; Fraser, John F. ; Davis, Melissa J. ; Belz, Gabrielle ; Warkiani, Majid ; Gallo, Carlos Salomon ; Souza-Fonseca-Guimaraes, Fernando ; Nguyen, Quan ; Mclean, Anthony ; Kulasinghe, Arutha ; Short, Kirsty R. ; Tang, Benjamin
Background: 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. Methods: We conducted a multi-cohort observational study to investigate the biol. and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients. Findings: We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression is associated with the presence of a high viral load. We further demonstrate that systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 severity. For clin. outcome prediction (e.g. respiratory failure), IFI27 expression displays a high pos. (0.83) and neg. (0.95) predictive value, outperforming all other known predictors of COVID-19 severity. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 swine influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients. Interpretation: These data suggest that prognostic biomarkers targeting the family of IFI27 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.