Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection

Journal of Translational Medicine

Emanuele Nicastri¹  Fabrizio Palmieri¹  Gina Gualano¹  Assunta Navarra²  Antonio Bertoletti³  Giuseppe Ippolito⁴  Elisa Petruccioli⁵  Delia Goletti⁵  Saeid Najafi Fard⁵  Linda Petrone⁵  Gilda Cuzzi⁵  Valentina Vanini⁶  Luca Pierelli⁷ 

[1] Clinical Division of Infectious Diseases, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy;Clinical Epidemiology Unit, National Institute for Infectious Disease Lazzaro Spallanzani-IRCCS, Rome, Italy;Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore;Scientific Direction, National Institute for Infectious Disease “Lazzaro Spallanzani”-IRCCS, Rome, Italy;Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy;Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy;UOS Professioni Sanitarie Tecniche National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy;UOC Transfusion Medicine and Stem Cell Unit, San Camillo Forlanini Hospital, Rome, Italy;

关键词: SARS-CoV-2;    COVID-19;    Biomarkers;    T-cell;    Immunity;    IP-10;    Whole-blood;    Immune response;    Spike;    IFN-γ;   

DOI  :  10.1186/s12967-021-02938-8

来源: Springer

【 摘 要 】

BackgroundRecent studies proposed the whole-blood based IFN-γ-release assay to study the antigen-specific SARS-CoV-2 response. Since the early prediction of disease progression could help to assess the optimal treatment strategies, an integrated knowledge of T-cell and antibody response lays the foundation to develop biomarkers monitoring the COVID-19. Whole-blood-platform tests based on the immune response detection to SARS-CoV2 peptides is a new approach to discriminate COVID-19-patients from uninfected-individuals and to evaluate the immunogenicity of vaccine candidates, monitoring the immune response in vaccine trial and supporting the serological diagnostics results. Here, we aimed to identify in the whole-blood-platform the best immunogenic viral antigen and the best immune biomarker to identify COVID-19-patients.MethodsWhole-blood was overnight-stimulated with SARS-CoV-2 peptide pools of nucleoprotein-(NP) Membrane-, ORF3a- and Spike-protein. We evaluated: IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL- 15, IL-17A, eotaxin, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, RANTES, TNF-α, VEGF. By a sparse partial least squares discriminant analysis we identified the most important soluble factors discriminating COVID-19- from NO-COVID-19-individuals.ResultsWe identified a COVID-19 signature based on six immune factors: IFN-γ, IP-10 and IL-2 induced by Spike; RANTES and IP-10 induced by NP and IL-2 induced by ORF3a. We demonstrated that the test based on IP-10 induced by Spike had the highest AUC (0.85, p  <  0.0001) and that the clinical characteristics of the COVID-19-patients did not affect IP-10 production. Finally, we validated the use of IP-10 as biomarker for SARS-CoV2 infection in two additional COVID-19-patients cohorts.ConclusionsWe set-up a whole-blood assay identifying the best antigen to induce a T-cell response and the best biomarkers for SARS-CoV-2 infection evaluating patients with acute COVID-19 and recovered patients. We focused on IP-10, already described as a potential biomarker for other infectious disease such as tuberculosis and HCV. An additional application of this test is the evaluation of immune response in SARS-CoV-2 vaccine trials: the IP-10 detection may define the immunogenicity of a Spike-based vaccine, whereas the immune response to the virus may be evaluated detecting other soluble factors induced by other viral-antigens.

【 授权许可】

CC BY