Integrative multi-omics approach to analyse long COVID

To precisely characterise immunological alterations in long COVID at both cellular and molecular levels, the interdisciplinary research team applied an integrative multi-omics approach. Single-cell RNA sequencing of peripheral immune cells was combined with comprehensive immune phenotyping, molecular inflammatory marker profiling, and clinical lung function data. This systems immunology strategy enabled direct linkage of systemic immune processes with functional pulmonary impairment and allowed the identification of disease-associated cell states at unprecedented resolution.

“A central focus of our work is to analyse complex immunological processes across multiple molecular layers using computational and statistical methods,” explains Prof. Dr. Yang Li, researcher at the DZL site BREATH and Director of the Centre for Individualised Infection Medicine (CiiM), jointly operated by Hannover Medical School and the Helmholtz Centre for Infection Research. “By integrating single-cell data, additional omics layers, and clinical parameters such as lung function, we can systematically capture genetic and immunological determinants and more precisely describe their contribution to infectious and immune-mediated diseases such as long COVID.”

Identification of a disease-associated monocyte cell state

A key finding of the study is the identification of a specific transcriptional state in circulating monocytes that is significantly enriched in patients with long COVID. This cell state is characterised by coordinated activation of multiple signalling pathways, including TGF-β and WNT/β-catenin–dependent programmes associated with chronic inflammation, immune regulation, and tissue remodelling. The magnitude of this monocyte transcriptional profile closely correlated with impaired lung function and persistent respiratory symptoms, pointing to a direct link between systemic immune dysregulation and pulmonary function.

Translational relevance for diagnostics and therapy

These findings provide an important bridge between systemic immune regulation and pulmonary pathophysiology in long COVID, offering a biological framework to better understand and stratify clinically heterogeneous disease courses.

“In clinical care, we observe highly variable trajectories and symptom constellations among long COVID patients,” says Dr. Isabell Pink, BREATH scientist and Head of the Post-COVID Outpatient Clinic at the Department of Pneumology and Infectious Diseases at Hannover Medical School. “Identifying a clearly defined immunological cell state provides an important starting point to better explain this heterogeneity and, in the long term, to develop more targeted diagnostic and therapeutic strategies.”

Original publication:
Kumar, S., Li, C., Zhou, L. et al. A distinct monocyte transcriptional state links systemic immune dysregulation to pulmonary impairment in long COVID. Nat Immunol (2026). 

Text: BREATH/AB

Photo: Isabell Pink: private; Yang Li: Nico Herzog; Thomas Illig: MHH/ Tom Figiel