# Principal component analysis of cytokine signature in COVID-19 and Long COVID

**Authors:** Zoia R. Korobova, Areg A. Totolian

PMC · DOI: 10.3389/fimmu.2026.1717107 · Frontiers in Immunology · 2026-02-26

## TL;DR

This study uses principal component analysis to identify key cytokine clusters in Long COVID, revealing complex immune system patterns.

## Contribution

The paper introduces a novel PCA-based approach to analyze cytokine interactions in Long COVID patients.

## Key findings

- Three key cytokine clusters were identified, each associated with different immune processes in Long COVID.
- Cluster A reflects local immune responses, while cluster B is linked to neuroinflammation.
- Cluster C indicates vascular changes, highlighting the complexity of Long COVID immunopathology.

## Abstract

Despite the activity of the COVID-19 pandemic being lower in the recent years, COVID-associated threat, long COVID (LC). Its clinical presentation includes nearly 200 symptoms affecting cardiovascular, respiratory, nervous systems, endocrine organs, urinary tract, and gastrointestinal systems. Cytokines serve as important biomarkers for assessing the level of immune system involvement and dysregulation in LC. Most studies on cytokine network and cytokine interactions usually address more traditional methods of statistical analysis with comparison criteria, discriminant analysis, regression. But multiplex cytokine analysis includes dozens of parameters, and requires complex assessment of the network as a whole.

We analyzed data of cytokine multiplex analysis of 289 patients with COVID-19, 44 patients with LC and 51 healthy donors. PCA we identified cyotkines with the highest importance rate, and further investigated between them with the use of 3D mapping.

Three key clusters were identified: cluster A - IL-13, CCL7/MCP-3, IL-4; cluster B - IL-18, CCL2/MCP-1, CCL4/MIP-1β, CXCL8/IL-8, M-CSF, and cluster C - sCD40L, CXCL1/GROα, PDGF-AA, EGF, FGF-2, FLT-3L, IL-7, IL-17F.

The coordinated interactions within these clusters reveal a complex immunopathology behind LC: clsuter A repsresenting local immune responses, cluster B for neuroinflammatory processes, and cluster C for changes in the blood vessels. The results, however, leave an opening for further investigatoin and interpretation.

## Linked entities

- **Proteins:** IL13 (interleukin 13), IL4 (interleukin 4), IL18 (interleukin 18), CSF1 (colony stimulating factor 1), pdgfaa (platelet-derived growth factor alpha polypeptide a), EGF (epidermal growth factor), FGF2 (fibroblast growth factor 2), FLT3LG (fms related receptor tyrosine kinase 3 ligand), IL7 (interleukin 7), IL17F (interleukin 17F)
- **Diseases:** COVID-19 (MONDO:0100096)

## Full-text entities

- **Genes:** FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, CSF1 (colony stimulating factor 1) [NCBI Gene 1435] {aka CSF-1, MCSF, PG-M-CSF}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, IL17F (interleukin 17F) [NCBI Gene 112744] {aka CANDF6, IL-17F, ML-1, ML1}, IL7 (interleukin 7) [NCBI Gene 3574] {aka IL-7, IMD130}, CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351] {aka ACT2, AT744.1, G-26, HC21, LAG-1, LAG1}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, CXCL1 (C-X-C motif chemokine ligand 1) [NCBI Gene 2919] {aka FSP, GRO1, GROa, MGSA, MGSA-a, NAP-3}, CCL7 (C-C motif chemokine ligand 7) [NCBI Gene 6354] {aka FIC, MARC, MCP-3, MCP3, NC28, SCYA6}, FLT3LG (fms related receptor tyrosine kinase 3 ligand) [NCBI Gene 2323] {aka FL, FLG3L, FLT3L, IMD125}
- **Diseases:** COVID (MESH:D000086382), LC (MESH:D000094024), neuroinflammatory (MESH:D000090862)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12979545/full.md

## References

54 references — full list in the complete paper: https://tomesphere.com/paper/PMC12979545/full.md

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Source: https://tomesphere.com/paper/PMC12979545