Exploratory principal component analysis (PCA) revealed a trend toward separation of vaccinated and non-vaccinated groups, suggestively driven by inflammatory cytokines (IL-6, TNF-α, GM-CSF, IL-18) and neutrophil surface markers (HLA-DR, PD-L1, TREM-1, CD16).<h4>Conclusions</h4>These findings suggest that prior COVID-19 vaccination is associated with a distinct neutrophil activation profile in patients with severe disease, characterized by the concomitant expression of pro-inflammatory and immunoregulatory markers. This evidence concerns the gene CSF2 and COVID-19.