{ "abstract": "Introduction: Long COVID is a complex pathophysiological condition linked to a heterogenous symptom profile. Dysregulation of 1) immunological and inflammatory responses, 2) endothelial/vascular function, and 3) metabolic and clotting processes have been identified; however, there remains a lack of clinically validated diagnostic biomarkers. The study aim was to investigate dysregulation of cytokines, chemokines and growth factors in confirmed Long COVID cases grouped by disease severity. Methods: One-hundred-and-twenty-seven participants provided venous blood samples for cytokine profiling utilising Luminex assays. Participants were grouped into those with no knowledge of SARS-CoV-2 infection (n = 21), acute infection within 3-months (n = 22), spontaneous resolvers (>3-months, n = 21) and those with confirmed Long COVID (n = 63). Long COVID severity was grouped according to the post-COVID-19 functional status (PCFS) and defined as those with negligible (4A; n = 9), mild (4B; n = 20), moderate (4C; n = 24), and severe limitations (4D; n = 10). Cytokines were assessed for normality using Shapiro-Wilk tests and differences measured between groups using Kruskal-Wallis tests. Pairwise correlation and principal component analysis were performed. Results: Interleukin-12 (p40/p70) was 22% greater in the Long COVID group (Median [IQR]: 58 [49] pg/mL, p = 0.046) and 30% greater in the acutely infected group (64 [36] pg/mL; p = 0.039) against non-infected controls (45 [25] pg/mL). Following PCFS classification, fibroblast growth factor-basic was 25% lower in Long COVID 4B versus spontaneous resolvers (24 [7] vs. 32 [24] pg/mL; p = 0.025). Pairwise correlation differences demonstrated that three Long COVID subgroups had strong, positive associations between cytokines when compared to non-infected controls; however, PCA was unable to determine any coordinated cytokine variation that was group specific. Discussion and conclusions: Elevated interleukin-12 (p40/p70) and reduced basic fibroblast growth factor suggest persistent immune activation and possible subgroup-specific Long COVID; however, these findings were marginally significant and exploratory. A coordinated but partial immunological/inflammatory profile may exist in some of those with Long COVID, suggesting a rationale for subgrouping upon a biological, rather than self-report basis but larger longitudinal studies are required to confirm this hypothesis.", "abstract_shown": true, "affiliations": [ "School of Health, Sport and Rehabilitation, College of Health and Humanities, University of Derby, Derby, United Kingdom.", "Research Centre for Healthcare and Communities Transformation, Coventry University, Coventry, United Kingdom.", "Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa.", "Department of Economics, Faculty of Economic and Management Sciences, Stellenbosch University, Stellenbosch, South Africa.", "School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, United Kingdom." ], "article_type": "Research Article", "arxiv": null, "author_total": 9, "authors": [ { "affs": [ 0 ], "name": "Callum Thomas", "orcid": "0000-0001-8608-8231" }, { "affs": [ 1 ], "name": "Ruth E Ashton", "orcid": "0000-0001-6282-0352" }, { "affs": [ 2 ], "name": "Etheresia Pretorius", "orcid": "0000-0002-9108-2384" }, { "affs": [ 0 ], "name": "Rebecca Owen" }, { "affs": [ 2 ], "name": "Massimo Nunes" }, { "affs": [ 3 ], "name": "Jan H Pretorius" }, { "affs": [ 0 ], "name": "Isaac T Shawa" }, { "affs": [ 0 ], "name": "Corinna Chidley" }, { "affs": [ 4 ], "name": "Mark A Faghy", "orcid": "0000-0002-8163-7032" } ], "bibtex": "https://research.draconitic.com/paper/1btqm6ahadzvw.bib", "cited_by": 0, "doi": "10.1371/journal.pone.0360525", "fulltext_url": "https://europepmc.org/articles/PMC13686509", "id": "1btqm6ahadzvw", "issns": [ "1932-6203" ], "landing_url": "https://doi.org/10.1371/journal.pone.0360525", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2728|Long-Term Effects of COVID-19" ], [ "plos", "/Biology and life sciences/Anatomy/Body fluids/Blood" ], [ "plos", "/Biology and life sciences/Biochemistry/Biomarkers" ], [ "plos", "/Biology and life sciences/Developmental biology/Molecular development/Cytokines" ], [ "plos", "/Biology and life sciences/Immunology/Immune response/Inflammation" ], [ "plos", "/Biology and life sciences/Immunology/Immune system/Innate immune system/Cytokines" ], [ "plos", "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Coronaviruses/SARS coronavirus/SARS CoV 2" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/RNA viruses/Coronaviruses/SARS coronavirus/SARS CoV 2" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Coronaviruses/SARS coronavirus/SARS CoV 2" ], [ "plos", "/Biology and life sciences/Physiology/Body fluids/Blood" ], [ "plos", "/Biology and life sciences/Physiology/Immune physiology/Cytokines" ], [ "plos", "/Engineering and technology/Electronics engineering/Electronics/Comparators" ], [ "plos", "/Medicine and health sciences/Anatomy/Body fluids/Blood" ], [ "plos", "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Inflammation" ], [ "plos", "/Medicine and health sciences/Diagnostic medicine/Virus testing" ], [ "plos", "/Medicine and health sciences/Immunology/Immune response/Inflammation" ], [ "plos", "/Medicine and health sciences/Immunology/Immune system/Innate immune system/Cytokines" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Coronaviruses/SARS coronavirus/SARS CoV 2" ], [ "plos", "/Physical sciences/Mathematics/Statistics/Statistical methods/Multivariate analysis/Principal component analysis" ], [ "plos", "/Research and analysis methods/Mathematical and statistical techniques/Statistical methods/Multivariate analysis/Principal component analysis" ] ], "openalex": "W7223111616", "pdf_url": "https://europepmc.org/articles/PMC13686509?pdf=render", "pmcid": "PMC13686509", "pmid": "42905724", "published": "2026-10-21", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/1btqm6ahadzvw.ris", "sources": [ { "first_seen": "2026-10-30T12:17:23Z", "native_id": "10.1371/journal.pone.0360525", "source": "plos", "url": "https://doi.org/10.1371/journal.pone.0360525" }, { "first_seen": "2026-10-30T12:19:53Z", "native_id": "MED:42905724", "source": "europepmc", "url": "https://europepmc.org/article/MED/42905724" } ], "subjects": [ { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" }, { "field": "mathematics", "origin": "plos:statistical methods", "subfield": "statistics" }, { "field": "medicine", "origin": "plos:anatomy", "subfield": "physiology" } ], "title": "Blood biomarkers of long COVID: A cross-sectional evaluation of key cytokines and the coordination of inflammation", "title_text": "Blood biomarkers of long COVID: A cross-sectional evaluation of key cytokines and the coordination of inflammation", "type": "peer-reviewed", "updated_at": "2026-10-30T12:19:53Z", "url": "https://research.draconitic.com/paper/1btqm6ahadzvw", "venue": "PLOS One", "versions": [] }