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. 2025 Apr;13(4):e70194.
doi: 10.1002/iid3.70194.

Altered Circulating Cytokine Profile Among mRNA-Vaccinated Young Adults: A Year-Long Follow-Up Study

Amani Alghamdi  1 , Syed Danish Hussain  1 , Kaiser Wani  1 , Shaun Sabico  1 , Abdullah M Alnaami  1 , Osama Emam Amer  1 , Nasser M Al-Daghri  1
Affiliations

Altered Circulating Cytokine Profile Among mRNA-Vaccinated Young Adults: A Year-Long Follow-Up Study

Amani Alghamdi et al. Immun Inflamm Dis. 2025 Apr.

Abstract

Objectives: This longitudinal study aimed to assess the impact of COVID-19 vaccination on cytokine profile.

Methods: A total of 84 Saudi subjects (57.1% females) with mean age of 27.2 ± 12.3 participated in this longitudinal study. Anthropometric data and fasting blood samples were obtained at baseline and after final vaccination, with an average follow-up duration of 14.1 ± 3.6 months for adolescents and 13.3 ± 3.0 months for adults, calculated from the first dose of vaccination. Assessment of cytokine profiles was done using commercially available assays.

Results: After follow-up, a significant increase in weight and body mass index was observed overall (p = 0.003 and p = 0.002, respectively). Postvaccination, significant increases were observed in several cytokines, including basic fibroblast growth factor 2 (p < 0.001), interferon gamma (IFNγ) (p = 0.005), interleukin-1 beta (IL1β) (p < 0.001), IL4 (p < 0.001), IL6 (p = 0.003), IL7 (p = 0.001), IL17E (p < 0.001), monocyte chemoattractant protein-1 (MCP1) (p = 0.03), MCP3 (p = 0.001), tumor necrosis factor alpha (TNFα) (p < 0.001), and VEGFA (p < 0.001). A significant reduction was observed only in macrophage colony-stimulating factor (p < 0.001). When adjusted for age, epidermal growth factor (EGF), IL4, IL6, MCP3, TNFα, and vascular endothelial growth factor (VEGFA) remained statistically significant. Gender-based analysis revealed that men experienced greater increases in IL6 (p = 0.008), IL4 (p = 0.04), and TNFα (p = 0.015) compared to women. Age-based analysis showed that older participants had more pronounced increases in EGF (p = 0.011), IL6 (p = 0.029), MCP1 (p = 0.042), and TNFα (p = 0.017), while younger participants had a greater increase in VEGFA (p = 0.025).

Conclusions: The findings of this study indicated that COVID-19 vaccination resulted in an increase in cytokine levels, which signifies the persistence of the humoral immune response to messenger RNA (mRNA) vaccines. This effect may be attributed to the persistent production of spike protein and highly inflammatory nature of mRNA-lipid nanoparticle. Additionally, the results suggested differences in cytokine levels based on gender and age. Notably, the cytokine profile remains favorably altered in young adults who received mRNA vaccinations, even after 1 year.

Keywords: COVID‐19 vaccination; age; cytokines; gender.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Log2 fold change in biomarkers postvaccination among select groups.
Figure 2
Figure 2
Correlation between log2 fold change postvaccination among serum cytokines.
See this image and copyright information in PMC

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