tetano
Editor, Senior Moderator
Front Immunol
. 2025 Nov 7:16:1710783.
doi: 10.3389/fimmu.2025.1710783. eCollection 2025. Transcriptome analysis of classical blood cells reveals downregulation of pro-inflammatory genes in the classical monocytes of long COVID patients
Florian Fricke[SUP] 1 [/SUP], Franz Mai[SUP] 1 [/SUP], Christine Wossidlo[SUP] 2 [/SUP], Felix Steinbeck[SUP] 1 3 [/SUP], Wendy Bergmann-Ewert[SUP] 1 [/SUP], Marcel Kordt[SUP] 1 [/SUP], Karin Kraft[SUP] 4 [/SUP], Britta Müller[SUP] 5 [/SUP], Emil C Reisinger[SUP] 2 [/SUP], Brigitte Müller-Hilke[SUP] 1 [/SUP]
Affiliations
Introduction: Despite extensive research, the pathogenesis and predispositions underlying long COVID (long-term coronavirus disease 2019) remain poorly understood.
Methods: To address this, we analyzed the immunological landscapes of 44 patients with long COVID and 44 matched convalescents using single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and validated the findings with plasma cytokine measurements via Luminex technology.
Results: While the immune cell compositions showed minimal quantitative differences only among natural killer (NK) cells, the transcriptome analyses identified distinct gene expression patterns, particularly in classical monocytes: patients with long COVID exhibited downregulation of the inflammation-associated genes, including IL1B and CXCL2. Imputation of the transcription factor activity hinted at a reduced inflammasome activity (via SNAI1) and an impaired monocyte differentiation (via ATF2) in long COVID. The RNA velocity data supported the presence of immature classical monocytes in these patients.
Discussion: These findings show that monocytes might be dysregulated and/or exhausted in patients with long COVID.
Keywords: SARS-CoV-2; immune landscape; immune tolerance; long COVID; monocytes; scRNAseq.
. 2025 Nov 7:16:1710783.
doi: 10.3389/fimmu.2025.1710783. eCollection 2025. Transcriptome analysis of classical blood cells reveals downregulation of pro-inflammatory genes in the classical monocytes of long COVID patients
Florian Fricke[SUP] 1 [/SUP], Franz Mai[SUP] 1 [/SUP], Christine Wossidlo[SUP] 2 [/SUP], Felix Steinbeck[SUP] 1 3 [/SUP], Wendy Bergmann-Ewert[SUP] 1 [/SUP], Marcel Kordt[SUP] 1 [/SUP], Karin Kraft[SUP] 4 [/SUP], Britta Müller[SUP] 5 [/SUP], Emil C Reisinger[SUP] 2 [/SUP], Brigitte Müller-Hilke[SUP] 1 [/SUP]
Affiliations
- PMID: 41280901
- PMCID: PMC12634634
- DOI: 10.3389/fimmu.2025.1710783
Introduction: Despite extensive research, the pathogenesis and predispositions underlying long COVID (long-term coronavirus disease 2019) remain poorly understood.
Methods: To address this, we analyzed the immunological landscapes of 44 patients with long COVID and 44 matched convalescents using single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and validated the findings with plasma cytokine measurements via Luminex technology.
Results: While the immune cell compositions showed minimal quantitative differences only among natural killer (NK) cells, the transcriptome analyses identified distinct gene expression patterns, particularly in classical monocytes: patients with long COVID exhibited downregulation of the inflammation-associated genes, including IL1B and CXCL2. Imputation of the transcription factor activity hinted at a reduced inflammasome activity (via SNAI1) and an impaired monocyte differentiation (via ATF2) in long COVID. The RNA velocity data supported the presence of immature classical monocytes in these patients.
Discussion: These findings show that monocytes might be dysregulated and/or exhausted in patients with long COVID.
Keywords: SARS-CoV-2; immune landscape; immune tolerance; long COVID; monocytes; scRNAseq.