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Researchers from Borstel, Lübeck, and Kiel identify two key messengers that trigger persistent inflammation in the nasal mucosa.Publication in Nature Communications.
A research team from the Research Center Borstel, Leibniz Lung Center (FZB), Kiel University (CAU), the University of Lübeck (UzL), and the University Medical Center Schleswig-Holstein (UKSH), together with additional partners, has gained new insights into the development of post-COVID syndrome. Using state-of-the-art single-cell transcriptomics (scRNA-seq) combined with cell biology models, the scientists were able to decipher the cellular and molecular mechanisms underlying the prolonged symptoms experienced by many affected individuals. The study identified two messenger substances that cause persistent inflammation in the nasal mucosa. This inflammatory process appears to inhibit tissue regeneration and thus contributes to the ongoing symptoms of post-COVID syndrome. The findings have now been published in Nature Communications.
Post-COVID syndrome (PCS) affects approximately 3–17% of individuals following infection with the SARS-CoV-2 coronavirus. Those affected suffer from late or long-term effects with a wide range of symptoms, the causes of which remain largely unclear. The team led by Dr. Karosham Reddy and Professor Markus Weckmann (both FZB), Professor Hauke Busch, and Associate Professor Dr. Anke Fähnrich from the Medical Systems Biology group at the Lübeck Institute of Experimental Dermatology (LIED), examined nasal biopsy samples from 25 patients with post-COVID syndrome at the cellular and molecular levels. The samples were collected as part of NAPKON, a nationwide post-COVID cohort.
The researchers analyzed, among other things, the existing cell types and the signaling pathways through which the cells communicate. They discovered that the mucosa of the upper respiratory tract remains structurally altered even months after recovery from a SARS-CoV-2 infection – despite the absence of an active viral infection. In this context, they identified two key messenger substances: TNFα and TGFβ. These appear to be responsible for a persistent misprogramming of the mucosal cells. Dr. Reddy and Professor Markus Weckmann at FZB were able to confirm these findings in innovative human mucosal models.
“Our data show that the combination of the two messenger substances TNFα and TGFβ severely disrupts the regeneration of the ciliated epithelium,” explains Dr. Reddy. “The persistent inflammation in the nasal mucosa is therefore not maintained by the virus itself, but driven by these messengers,” Reddy continues. As a result, the airway mucosa can no longer maintain its protective function, which may lead to prolonged respiratory symptoms and increased susceptibility to infections, both typical features of PCS.
The results of the study may provide new approaches for targeted treatment of post-COVID syndrome. “Our observations point to specific signaling pathways that appear to play a key role in PCS. These could be therapeutically targeted to alleviate symptoms and possibly prevent long-term damage to the nasal mucosa,” says lead author PD Dr. Fähnrich. The mechanisms observed could also play a role in other chronic lung diseases, which will need to be explored in future studies.
The study is an example of successful interdisciplinary and translational research within the Cluster of Excellence Precision Medicine in Chronic Inflammation (PMI). The close collaboration between FZB, LIED at the University of Lübeck, and the University Medical Center Schleswig-Holstein (UKSH), as well as with the industrial partner Singleron, was crucial to its success. Only through this close cooperation was it possible to obtain high-quality single-cell data and analyze them using advanced bioinformatic methods.
Photos are available to download:
https://www.precisionmedicine.de/de/pressemitteilungen/pressebilder-2025/13-Team...
v.l.: PD Dr. Anke Fähnrich (LIED/UzL), Prof. Hauke Busch (LIED/UzL), Dr. Karosham Reddy (FZB), Prof. Markus Weckmann (FZB, UKSH, UzL), Yamil Maluje (LIED/UzL)
© W. Nurieva, Uni Lübeck
The Cluster of Excellence "Precision Medicine in Chronic Inflammation" (PMI) is being funded from 2019 to 2025 through the German Excellence Strategy (ExStra). It succeeds the "Inflammation at Interfaces” Cluster, which was already funded in two periods of the Excellence Initiative (2007-2018). Around 300 members from eight institutions at four locations are involved: Kiel (Kiel University, University Medical Center Schleswig-Holstein (UKSH), Muthesius University of Fine Arts and Design, Kiel Institute for the World Economy (IfW), Leibniz Institute for Science and Mathematics Education (IPN)), Lübeck (University of Lübeck, University Medical Center Schleswig-Holstein (UKSH)), Plön (Max Planck Institute for Evolutionary Biology) and Borstel (Research Center Borstel - Leibniz Lung Center).
The goal is to translate interdisciplinary research findings on chronic inflammatory diseases of barrier organs to healthcare more intensively, as well as to fulfill previously unsatisfied needs of the patients. Three points are important in the context of successful treatment, and are therefore at the heart of PMI research: the early detection of chronic inflammatory diseases, the prediction of disease progression and complications, and the prediction of individual responses to treatment.
Cluster of Excellence "Precision Medicine in Chronic Inflammation"
Scientific Office, Head: Dr habil. Susanne Holstein
Postal address: Christian-Albrechts-Platz 4, 24118 Kiel, Germany
Contact: Sonja Petermann
Tel.: +49 (0)431 880-4850, Fax: +49 (0)431 880-4894
E-mail: spetermann@uv.uni-kiel.de
Twitter: PMI @medinflame
Press Contact:
Frederike Buhse
Phone: +49 431 880 4682
email: fbuhse@uv.uni-kiel.de
https://precisionmedicine.de
Link to the press information: https://www.precisionmedicine.de/en/details/news/new-study-uncovers-molecular-dr...
PD Dr. habil. Anke Fähnrich
Medizinische Systembiologie, Lübecker Institut für Experimentelle Dermatologie
Universität zu Lübeck und Universitätsklinikum Schleswig-Holstein (UKSH), Campus Lübeck
Phone: +49 451/ 3101 8473
E-Mail: anke.faehnrich@uksh.de
Reddy, K.D., Maluje, Y., Ott, F. et al.: scRNA-seq reveals persistent aberrant differentiation of nasal epithelium driven by TNFα and TGFβ in post-COVID syndrome. Nat Commun (2025). https://doi.org/10.1038/s41467-025-64778-0
from left: PD Dr. Anke Fähnrich (LIED/UzL), Prof. Hauke Busch (LIED/UzL), Dr. Karosham Reddy (FZB), ...
Quelle: W. Nurieva
Copyright: University of Lübeck
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Biologie, Ernährung / Gesundheit / Pflege, Medizin
überregional
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from left: PD Dr. Anke Fähnrich (LIED/UzL), Prof. Hauke Busch (LIED/UzL), Dr. Karosham Reddy (FZB), ...
Quelle: W. Nurieva
Copyright: University of Lübeck
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