tetano
Editor, Senior Moderator
Mol Biol Rep
. 2026 Apr 11;53(1):610.
doi: 10.1007/s11033-026-11778-y.
COVID-19 vaccination shifts neutrophils toward a mixed activated and regulatory phenotype in patients with severe disease
Yrna Lorena M de Oliveira[SUP] 1 2 [/SUP], Ayane de S Resende[SUP] 3 [/SUP], Mariana N F de Franca[SUP] 3 [/SUP], Camilla Natália O Santos[SUP] 3 4 5 [/SUP], Lucas S Magalhães[SUP] 4 6 [/SUP], Cristiane B Correa[SUP] 3 7 [/SUP], Priscila L Dos S Almeida[SUP] 3 4 [/SUP], Angela Maria da Silva[SUP] 3 4 [/SUP], Michael W Lipscomb[SUP] 8 [/SUP], Tatiana R de Moura[SUP] 3 4 [/SUP]
Affiliations
Background: Dysregulation of the innate immune response to SARS-CoV-2 has been linked to poor outcomes in COVID-19. Neutrophils are key players in this response, displaying distinct functional profiles associated with disease severity. This study investigates how neutrophil phenotypes, and their mediators are modulated in severe COVID-19 following vaccination.
Methods and results: We conducted an observational case-control study using clinical data, serum samples, and circulating neutrophils from patients hospitalized with severe COVID-19. Neutrophils from vaccinated patients exhibited increased expression of surface markers including TREM-1, CD182, HLA-DR, and PD-L1, alongside higher HLA-DR mean fluorescence intensity (MFI). These cells also showed a higher proportion of inflammatory (CD16⁺CD182⁺TREM-1⁺) and immunoregulatory (HLA-DR⁺PD-L1⁺) subsets compared to non-vaccinated individuals. 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).
Conclusions: 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 immune phenotype may reflect a more balanced inflammatory response during severe SARS-CoV-2 infection. These findings open avenues for future studies incorporating functional assays and larger, independent cohorts to confirm and extend the biological and clinical relevance of these observations.
Keywords: Innate immunity; Neutrophils; SARS-CoV-2; TREM-1.
. 2026 Apr 11;53(1):610.
doi: 10.1007/s11033-026-11778-y.
COVID-19 vaccination shifts neutrophils toward a mixed activated and regulatory phenotype in patients with severe disease
Yrna Lorena M de Oliveira[SUP] 1 2 [/SUP], Ayane de S Resende[SUP] 3 [/SUP], Mariana N F de Franca[SUP] 3 [/SUP], Camilla Natália O Santos[SUP] 3 4 5 [/SUP], Lucas S Magalhães[SUP] 4 6 [/SUP], Cristiane B Correa[SUP] 3 7 [/SUP], Priscila L Dos S Almeida[SUP] 3 4 [/SUP], Angela Maria da Silva[SUP] 3 4 [/SUP], Michael W Lipscomb[SUP] 8 [/SUP], Tatiana R de Moura[SUP] 3 4 [/SUP]
Affiliations
- PMID: 41964802
- PMCID: PMC13070084
- DOI: 10.1007/s11033-026-11778-y
Background: Dysregulation of the innate immune response to SARS-CoV-2 has been linked to poor outcomes in COVID-19. Neutrophils are key players in this response, displaying distinct functional profiles associated with disease severity. This study investigates how neutrophil phenotypes, and their mediators are modulated in severe COVID-19 following vaccination.
Methods and results: We conducted an observational case-control study using clinical data, serum samples, and circulating neutrophils from patients hospitalized with severe COVID-19. Neutrophils from vaccinated patients exhibited increased expression of surface markers including TREM-1, CD182, HLA-DR, and PD-L1, alongside higher HLA-DR mean fluorescence intensity (MFI). These cells also showed a higher proportion of inflammatory (CD16⁺CD182⁺TREM-1⁺) and immunoregulatory (HLA-DR⁺PD-L1⁺) subsets compared to non-vaccinated individuals. 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).
Conclusions: 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 immune phenotype may reflect a more balanced inflammatory response during severe SARS-CoV-2 infection. These findings open avenues for future studies incorporating functional assays and larger, independent cohorts to confirm and extend the biological and clinical relevance of these observations.
Keywords: Innate immunity; Neutrophils; SARS-CoV-2; TREM-1.