High levels of pro-inflammatory SARS-CoV-2-specific biomarkers revealed by in vitro whole blood cytokine release assay (CRA) in recovered and long-COVID-19 patients.

Autor: Gomes SMR; Department of Microbiology, Parasitology and Immunology, Medical Science Faculty (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil., Brito ACS; Department of Microbiology, Parasitology and Immunology, Medical Science Faculty (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil., Manfro WFP; Department of Microbiology, Parasitology and Immunology, Medical Science Faculty (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil., Ribeiro-Alves M; Laboratory of Clinical Research on STD/AIDS, National Institute of Infectology Evandro Chagas, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, RJ, Brazil., Ribeiro RSA; Laboratory of Immunopathology, Department of General Pathology and Laboratories, FCM, UERJ, Rio de Janeiro, RJ, Brazil., da Cal MS; Pulmonary and Tisiology Department, Pedro Ernesto University Hospital (HUPE), Policlínica Piquet Carneiro (PPC)/UERJ, Rio de Janeiro, RJ, Brazil., Lisboa VDC; Laboratory of Immunopathology, Department of General Pathology and Laboratories, FCM, UERJ, Rio de Janeiro, RJ, Brazil., Abreu DPB; Chemical Engineering Program, Cell Culture Engineering Lab (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil., Castilho LDR; Chemical Engineering Program, Cell Culture Engineering Lab (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil., Porto LCMS; Histocompatibility and Cryopreservation Laboratory, Department of Histology and Embryology Institute of Biology Roberto Alcantara Gomes, UERJ, Rio de Janeiro, RJ, Brazil., Mafort TT; Pulmonary and Tisiology Department, Pedro Ernesto University Hospital (HUPE), Policlínica Piquet Carneiro (PPC)/UERJ, Rio de Janeiro, RJ, Brazil., Lopes AJ; Pulmonary and Tisiology Department, Pedro Ernesto University Hospital (HUPE), Policlínica Piquet Carneiro (PPC)/UERJ, Rio de Janeiro, RJ, Brazil., da Silva SAG; Department of Microbiology, Parasitology and Immunology, Medical Science Faculty (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil., Dutra PML; Department of Microbiology, Parasitology and Immunology, Medical Science Faculty (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil., Rodrigues LS; Laboratory of Immunopathology, Department of General Pathology and Laboratories, FCM, UERJ, Rio de Janeiro, RJ, Brazil.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Apr 05; Vol. 18 (4), pp. e0283983. Date of Electronic Publication: 2023 Apr 05 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0283983
Abstrakt: Background: Cytokines induced by SARS-CoV-2 infection play a crucial role in the pathophysiology of COVID-19 and hyperinflammatory responses have been associated with poor clinical outcomes, with progression to severe conditions or long-term subacute complications named as long-COVID-19.
Methods: In this cross-sectional study, we aimed to evaluate a set of antigen-specific inflammatory cytokines in blood from recovered COVID-19 individuals or who suffered a post-acute phase of SARS-CoV-2 infection compared to healthy individuals with no history of COVID-19 exposition or infection. Interferon-gamma (IFN-γ), IFN-γ-induced protein 10 (IP-10), tumor necrosis factor (TNF), IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, and IL-17A were quantified by multiplex cytometric bead assay and enzyme-linked immunosorbent assay after stimulation of whole blood with recombinant Spike protein from SARS-CoV-2. Additionally, all participants have evaluated for anti-(S) protein-specific IgG antibodies. Clinical specimens were collected within two months of COVID-19 diagnosis.
Results: A total of 47 individuals were enrolled in the study, a median age of 43 years (IQR = 14.5), grouped into healthy individuals with no history of infection or exposure to SARS-CoV-2 (unexposed group; N = 21); and patients from the Health Complex of the Rio de Janeiro State University (UERJ), Brazil, who were SARS-CoV-2 positive by RT-PCR (COVID-19 group)-categorized as recovered COVID-19 (N = 11) or long-COVID-19 (N = 15). All COVID-19 patients presented at least one signal or symptom during the first two weeks of infection. Six patients were hospitalized and required invasive mechanical ventilation. Our results showed that COVID-19 patients had significantly higher levels of IFN-γ, TNF, IL-1β, IL-2, IL-6, IL-8, and IP-10 than the unexposed group. The long-COVID-19 group has presented significantly high levels of IL-1β and IL-6 compared to unexposed individuals, but not from recovered COVID-19. A principal-component analysis demonstrated 84.3% of the total variance of inflammatory-SARS-CoV-2 response in the first two components, and it was possible to stratify IL-6, TNF, IL-1β, IL-10, and IL-2 as the top-five cytokines which are candidates to discriminate COVID-19 group (including long-COVID-19 subgroup) and healthy unexposed individuals.
Conclusion: We revealed important S protein-specific differential biomarkers in individuals affected by COVID-19, bringing new insights into the inflammatory status or SARS-CoV-2 exposition determination.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Gomes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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