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Published in: Journal of Translational Medicine 1/2021

Open Access 01-12-2021 | SARS-CoV-2 | Research

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

Authors: Elisa Petruccioli, Saeid Najafi Fard, Assunta Navarra, Linda Petrone, Valentina Vanini, Gilda Cuzzi, Gina Gualano, Luca Pierelli, Antonio Bertoletti, Emanuele Nicastri, Fabrizio Palmieri, Giuseppe Ippolito, Delia Goletti

Published in: Journal of Translational Medicine | Issue 1/2021

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Abstract

Background

Recent 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.

Methods

Whole-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.

Results

We 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.

Conclusions

We 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.
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Metadata
Title
Exploratory analysis to identify the best antigen and the best immune biomarkers to study SARS-CoV-2 infection
Authors
Elisa Petruccioli
Saeid Najafi Fard
Assunta Navarra
Linda Petrone
Valentina Vanini
Gilda Cuzzi
Gina Gualano
Luca Pierelli
Antonio Bertoletti
Emanuele Nicastri
Fabrizio Palmieri
Giuseppe Ippolito
Delia Goletti
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-021-02938-8

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