IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study
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Abstract
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 biology and the prognostic role of interferon alpha-inducible protein 27 ( IFI27 ) in COVID-19 patients.
Results
We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 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 IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27- like genes were highly upregulated in the blood samples of severely infected patients.
Conclusion
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.
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SciScore for 10.1101/2021.10.29.21265555: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study was approved by the Human Research Ethics Committees of participating institutions and all study participants provided informed consent.
Consent: The study was approved by the Human Research Ethics Committees of participating institutions and all study participants provided informed consent.
IACUC: All methods were performed in accordance with institutional guidelines and regulations.
Field Sample Permit: Cohort 6: This study was approved by the Mazandaran University of Medical Sciences (approval number IR.MAZUMS.REC 1399.856).Sex as a biological variable not detected. Randomization not detected. Blinding Researchers who performed PCR assays were blinded to information regarding … SciScore for 10.1101/2021.10.29.21265555: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study was approved by the Human Research Ethics Committees of participating institutions and all study participants provided informed consent.
Consent: The study was approved by the Human Research Ethics Committees of participating institutions and all study participants provided informed consent.
IACUC: All methods were performed in accordance with institutional guidelines and regulations.
Field Sample Permit: Cohort 6: This study was approved by the Mazandaran University of Medical Sciences (approval number IR.MAZUMS.REC 1399.856).Sex as a biological variable not detected. Randomization not detected. Blinding Researchers who performed PCR assays were blinded to information regarding patient data or etiological diagnoses. Power Analysis not detected. Cell Line Authentication Contamination: In addition to standard microbiological tests, testing for atypical respiratory pathogens (Chlamydophila pneumoniae, Mycoplasma pneumoniae and Legionella pneumonphila) was also performed in selected patients at the discretion of treating physicians. Table 2: Resources
Software and Algorithms Sentences Resources All statistical analyses were performed using Prism version 9.0. Prismsuggested: (PRISM, RRID:SCR_005375)Cohort 7: Singaporean cohort: The study was approved by the National Healthcare Group Domain Specific Review Board (DSRB 2014/00614). National Healthcaresuggested: NoneResults from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:The present study has several limitations. Firstly, the prospective validation cohort was relatively limited in size. Secondly, patient cohorts were recruited prior to the availability of vaccination. Accordingly, our findings do not apply to vaccinated individuals experiencing ‘breakthrough’ infections. Finally, we could not correlate the changes in IFI27 expression levels between the peripheral blood and the infected lung. Future studies (e.g., in animal models) are needed to unravel the coupled dynamics of IFI27 expression between these tissue compartments. In conclusion, the findings provided herein represent the first evidence that IFI27 expression has a potential as a severity biomarker for risk stratification in COVID-19 patients.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a protocol registration statement.
Results from scite Reference Check: We found no unreliable references.
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