Evidence map›Paper›PMID 37018291›Full record

ArticlePloS one2023

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.

Shayane Martins Rodrigues Gomes, Andréia Carolinne de Souza Brito, Wânia Ferraz Pereira Manfro, Marcelo Ribeiro-Alves, Roberto Stefan de Almeida Ribeiro, Mariana Soares da Cal, Vinicius da Cunha Lisboa, Daniel Paiva Barros de Abreu, Leda Dos Reis Castilho, Luís Cristóvão de Moares Sobrino Porto and 5 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Pooled it
  2. Human brain matters: Navigating the neuropathology of COVID-19.Brain pathology (Zurich, Switzerland) · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. A pain from the nose to the head: neurological commitment during long COVID.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  7. Association Between Genetic Variants inDiagnostics (Basel, Switzerland) · 2025
    Article
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  9. Article
  10. Article
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  12. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 1 country.

Shayane Martins Rodrigues GomesDepartment of Microbiology, Parasitology and Immunology, Medical Science Faculty (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil.
Andréia Carolinne de Souza BritoDepartment of Microbiology, Parasitology and Immunology, Medical Science Faculty (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil.
Wânia Ferraz Pereira ManfroDepartment of Microbiology, Parasitology and Immunology, Medical Science Faculty (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil.
Marcelo Ribeiro-AlvesLaboratory of Clinical Research on STD/AIDS, National Institute of Infectology Evandro Chagas, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, RJ, Brazil.
Roberto Stefan de Almeida RibeiroLaboratory of Immunopathology, Department of General Pathology and Laboratories, FCM, UERJ, Rio de Janeiro, RJ, Brazil.
Mariana Soares da CalPulmonary and Tisiology Department, Pedro Ernesto University Hospital (HUPE), Policlínica Piquet Carneiro (PPC)/UERJ, Rio de Janeiro, RJ, Brazil.ORCID 0000-0001-5537-7057
Vinicius da Cunha LisboaLaboratory of Immunopathology, Department of General Pathology and Laboratories, FCM, UERJ, Rio de Janeiro, RJ, Brazil.
Daniel Paiva Barros de AbreuChemical Engineering Program, Cell Culture Engineering Lab (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
Leda Dos Reis CastilhoChemical Engineering Program, Cell Culture Engineering Lab (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
Luís Cristóvão de Moares Sobrino PortoHistocompatibility and Cryopreservation Laboratory, Department of Histology and Embryology Institute of Biology Roberto Alcantara Gomes, UERJ, Rio de Janeiro, RJ, Brazil.
Thiago Thomáz MafortPulmonary and Tisiology Department, Pedro Ernesto University Hospital (HUPE), Policlínica Piquet Carneiro (PPC)/UERJ, Rio de Janeiro, RJ, Brazil.
Agnaldo José LopesPulmonary and Tisiology Department, Pedro Ernesto University Hospital (HUPE), Policlínica Piquet Carneiro (PPC)/UERJ, Rio de Janeiro, RJ, Brazil.ORCID 0000-0001-8598-4878
Silvia Amaral Gonçalves da SilvaDepartment of Microbiology, Parasitology and Immunology, Medical Science Faculty (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil.
Patrícia Maria Lourenço DutraDepartment of Microbiology, Parasitology and Immunology, Medical Science Faculty (FCM), Rio de Janeiro State University (UERJ), Rio de Janeiro, RJ, Brazil.
Luciana Silva RodriguesLaboratory of Immunopathology, Department of General Pathology and Laboratories, FCM, UERJ, Rio de Janeiro, RJ, Brazil.ORCID 0000-0003-0743-1009
Universidade do Estado do Rio de Janeiro · BRHospital Universitário Pedro Ernesto · BRUniversidade Federal do Rio de Janeiro · BRFundação Oswaldo Cruz · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCytokines 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.

methodsIn 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.

resultsA 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.

conclusionWe 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.

Indexed as

COVID-19CytokinesAdolescentBrazilChemokine CXCL10COVID-19 TestingCross-Sectional StudiesHumansInterferon-gammaInterleukin-10Interleukin-2Interleukin-6Interleukin-8Post-Acute COVID-19 SyndromeSARS-CoV-2Tumor Necrosis Factor-alphaChemokine CXCL10CytokinesInterferon-gammaInterleukin-10Interleukin-2Interleukin-6Interleukin-8Tumor Necrosis Factor-alpha

Identifiers

PMID37018291
PMCPMC10075475
OpenAlexW4362601316

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.