ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1710783
This article is part of the Research TopicThe Influence of SARS-CoV-2 Infection and Long-COVID on The Incidence of Viral CoinfectionView all 10 articles
Transcriptome analysis of classical blood cells reveals down-regulation of proinflammatory genes in the classical monocytes of Long-COVID patients
Provisionally accepted
Florian Fricke
Franz Mai
Christine WossidloFelix Steinbeck
Wendy Bergmann-Ewert
Marcel Kordt
Karin Kraft
Britta Müller
Emil Christian Reisinger
Brigitte Müller-Hilke*- University Hospital Rostock, Rostock, Germany
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Despite extensive research, the pathogenesis and predispositions underlying Long-COVID remain poorly understood. To address this, we analyzed the immunological landscapes of 44 Long-COVID patients and 44 matched convalescents using single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and validated findings with plasma cytokine measurements via Luminex technology. While immune cell compositions showed minimal quantitative differences only among NK cells, transcriptome analyses identified distinct gene expression patterns, particularly in classical monocytes: Long-COVID patients exhibited downregulation of inflammation-associated genes, including IL1B and CXCL2. Imputation of transcription factor activity hinted at reduced inflammasome activity (via SNAI1) and impaired monocyte differentiation (via ATF2) in Long-COVID. RNA velocity supported the presence of immature classical monocytes in patients. These findings showed that monocytes might be dysregulated and/or exhausted in Long-COVID patients.
Keywords: Immune landscape, Immune Tolerance, Monocytes, SARS-CoV-2, Long-covid, scRNAseq
Received: 22 Sep 2025; Accepted: 17 Oct 2025.
Copyright: © 2025 Fricke, Mai, Wossidlo, Steinbeck, Bergmann-Ewert, Kordt, Kraft, Müller, Reisinger and Müller-Hilke. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Brigitte Müller-Hilke, brigitte.mueller-hilke@med.uni-rostock.de
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