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.

1st Medical Department Faculty of Medicine in Pilsen Charles University Medical School and Teaching Hospital Plzen Pilsen Czech Republic

Azienda Sanitaria Locale 3 Genovese Genova Liguria Italy

Cancer Research Department Sidra Medicine Doha Qatar

Centre for Clinical Research in Emergency Medicine Royal Perth Hospital Perth Western Australia Australia

Centre for Immunology and Allergy Research Westmead Institute for Medical Research Westmead New South Wales Australia

Centre for Infectious Diseases and Microbiology Westmead Hospital Westmead New South Wales Australia

Department of Health Sciences University of Genoa Genova Liguria Italy

Department of Infection Genetics Helmholtz Centre for Infection Research Braunschweig Niedersachsen Germany

Department of Intensive Care Medicine Amiens University Hospital Amiens France

Department of Internal Medicine Medistra Hospital Jakarta Indonesia

Department of Internal Medicine University of Genoa Genova Italy

Department of Surgery National University Singapore Yong Loo Lin School of Medicine Singapore

Division of Infectious and Tropical Diseases IRCCS Ospedale Policlinico San Martino Genova Liguria Italy

Division of Internal Medicine and Oncology IRCCS Ospedale Policlinico San Martino Genova Italy

Division of Primary Care University of Nottingham Nottingham UK

Emergency Medicine National University Hospital Singapore

Ente Ospedaliero Ospedali Galliera Genova Liguria Italy

Immunology Department Sidra Medical and Research Center Doha Ad Dawhah Qatar

Mucosal Immunology Research Group Griffith University Menzies Health Institute Queensland Southport Queensland Australia

Nepean Clinical School University of Sydney Sydney New South Wales Australia

System Biology and Health Data Analytic Lab The Graduate School of Biomedical Engineering University of New South Wales Sydney New South Wales Australia

Tarumanagara University Faculty of Medicine Jakarta Barat Jakarta Indonesia

University of Veterinary Medicine Hannover Hannover Niedersachsen Germany

Westmead Institute for Medical Research Westmead New South Wales Australia

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Wu C, Chen X, Cai Y, et al. . Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020;180:934. 10.1001/jamainternmed.2020.0994 PubMed DOI PMC

Zhou F, Yu T, Du R, et al. . Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054–62. 10.1016/S0140-6736(20)30566-3 PubMed DOI PMC

Chen X, Zhao B, Qu Y. Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely associated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients. Medrxiv. 10.1101/2020.02.29.20029520 PubMed DOI PMC

Ling W. C-Reactive protein levels in the early stage of COVID-19. Med Mal Infect 2020. 10.1016/j.medmal.2020.03.007 PubMed DOI PMC

Wang F, Nie J, Wang H, et al. . Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia. J Infect Dis 2020;221:1762–9. 10.1093/infdis/jiaa150 PubMed DOI PMC

Tang BM, Shojaei M, Parnell GP, et al. . A novel immune biomarker IFI27 discriminates between influenza and bacteria in patients with suspected respiratory infection. Eur Respir J 2017;49:1602098. 10.1183/13993003.02098-2016 PubMed DOI

Tang BM, Shojaei M, Teoh S, et al. . Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection. Nat Commun 2019;10:3422. 10.1038/s41467-019-11249-y PubMed DOI PMC

Mayhew MB, Buturovic L, Luethy R, et al. . A generalizable 29-mRNA neural-network classifier for acute bacterial and viral infections. Nat Commun 2020;11:1177. 10.1038/s41467-020-14975-w PubMed DOI PMC

Collins GS, Reitsma JB, Altman DG, et al. . Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD). Circulation 2015;131:211–9. 10.1161/CIRCULATIONAHA.114.014508 PubMed DOI PMC

Bellary S, Krishnankutty B, Latha MS. Basics of case report form designing in clinical research. Perspect Clin Res 2014;5:159–66. 10.4103/2229-3485.140555 PubMed DOI PMC

Wynants L, Van Calster B, Collins GS, et al. . Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal. BMJ 2020;369:m1328. 10.1136/bmj.m1328 PubMed DOI PMC

Royston P. Multiple imputation of missing values: update. Stata J 2005;5:188–201. 10.1177/1536867X0500500204 DOI

Marshall A, Altman DG, Holder RL, et al. . Combining estimates of interest in prognostic modelling studies after multiple imputation: current practice and guidelines. BMC Med Res Methodol 2009;9:57. 10.1186/1471-2288-9-57 PubMed DOI PMC

Metz CE. Basic principles of ROC analysis. Semin Nucl Med 1978;8:283–98. 10.1016/S0001-2998(78)80014-2 PubMed DOI

Brown LD, Cai TT, science ADS. Interval estimation for a binomial proportion. Statist Sci 2001;16:101–33. 10.1214/ss/1009213286 DOI