Prospective validation study of prognostic biomarkers to predict adverse outcomes in patients with COVID-19: a study protocol
Open Access
- 6 January 2021
- Vol. 11 (1), e044497
- https://doi.org/10.1136/bmjopen-2020-044497
Abstract
Introduction Accurate triage is an important first step to effectively manage the clinical treatment of severe cases in a pandemic outbreak. In the current COVID-19 global pandemic, there is a lack of reliable clinical tools to assist clinicians to perform accurate triage. Host response biomarkers have recently shown promise in risk stratification of disease progression; however, the role of these biomarkers in predicting disease progression in patients with COVID-19 is unknown. Here, we present a protocol outlining a prospective validation study to evaluate the biomarkers’ performance in predicting clinical outcomes of patients with COVID-19. Methods and analysis This prospective validation study assesses patients infected with COVID-19, in whom blood samples are prospectively collected. Recruited patients include a range of infection severity from asymptomatic to critically ill patients, recruited from the community, outpatient clinics, emergency departments and hospitals. Study samples consist of peripheral blood samples collected into RNA-preserving (PAXgene/Tempus) tubes on patient presentation or immediately on study enrolment. Real-time PCR (RT-PCR) will be performed on total RNA extracted from collected blood samples using primers specific to host response gene expression biomarkers that have been previously identified in studies of respiratory viral infections. The RT-PCR data will be analysed to assess the diagnostic performance of individual biomarkers in predicting COVID-19-related outcomes, such as viral pneumonia, acute respiratory distress syndrome or bacterial pneumonia. Biomarker performance will be evaluated using sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operating characteristic curve. Ethics and dissemination This research protocol aims to study the host response gene expression biomarkers in severe respiratory viral infections with a pandemic potential (COVID-19). It has been approved by the local ethics committee with approval number 2020/ETH00886. The results of this project will be disseminated in international peer-reviewed scientific journals.Funding Information
- CREID
- APPRISE
- Amgen
- Associazione Italiana per la Ricerca sul Cancro (IG 2018 ID 21761)
- MHIQ
- National Institute of Allergy and Infectious Diseases (2-U19-AI100625-06 REVISED, 5U19A|100625-07)
- Ministerstvo Školství, Mládeže a Tělovýchovy (CZ.02.1.01/0.0/0.0/16_019/0000787)
- Griffith University
- Helmholtz Association
This publication has 14 references indexed in Scilit:
- Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort studyThe Lancet, 2020
- A generalizable 29-mRNA neural-network classifier for acute bacterial and viral infectionsNature Communications, 2020
- Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely associated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patientsPublished by Cold Spring Harbor Laboratory ,2020
- Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infectionNature Communications, 2019
- A novel immune biomarker IFI27 discriminates between influenza and bacteria in patients with suspected respiratory infectionEuropean Respiratory Journal, 2017
- Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD)Circulation, 2015
- Basics of case report form designing in clinical researchPerspectives in Clinical Research, 2014
- Combining estimates of interest in prognostic modelling studies after multiple imputation: current practice and guidelinesBMC Medical Research Methodology, 2009
- Multiple Imputation of Missing Values: UpdateThe Stata Journal: Promoting communications on statistics and Stata, 2005
- Basic principles of ROC analysisSeminars in Nuclear Medicine, 1978