A northern German research team has shown that two messenger substances are responsible for persistent inflammatory processes in the nasal mucosa in post-COVID syndrome: TNFα and TGFβ.
A research team from the Borstel Research Center, Leibniz Lung Center (FZB), the Christian Albrechts University of Kiel (CAU), the University of Lübeck (UzL) and the University Hospital Schleswig-Holstein (UKSH), together with other partners, has gained new insights into the development of the post-COVID syndrome. The researchers combined state-of-the-art single-cell transcriptomics (scRNA-seq) with cell biological models.
Inflammatory process inhibits tissue regeneration
This enabled them to decipher the cellular and molecular mechanisms behind the long-term complaints of many of those affected. The study identified two messenger substances that permanently trigger inflammation in the nasal mucosa. This inflammatory process apparently inhibits tissue regeneration and thus contributes to persistent symptoms in post-COVID. The results are currently published in “Nature Communications”.
Post-COVID syndrome (PCS) affects around 3 to 17 percent of people after an infection with the SARS-CoV-2 coronavirus. Those affected suffer from late or long-term consequences with different symptoms. The causes are still largely unclear.
The team around Dr. Karosham Reddy, Prof. Markus Weckmann (both FZB), Prof. Hauke Busch and PD Dr. Anke Fähnrich from Medical Systems Biology at the Lübeck Institute for Experimental Dermatology (LIED) therefore examined nasal biopsy samples from 25 patients with post-COVID syndrome at the cellular and molecular level. The samples were taken as part of NAPKON, a nationwide post-COVID cohort.
Persistent inflammation of the nasal mucosa driven by messenger substances
Among other things, the researchers analyzed the existing cell types and signaling pathways with which the cells communicate with each other. They found that the mucous membrane of the upper respiratory tract remains structurally changed months after a SARS-CoV-2 infection has been overcome – even if there is no longer an active viral infection. They identified two central messenger substances: TNFα and TGFβ. These are apparently responsible for persistent misprogramming of the mucosal cells. Reddy and Markus Weckmann at the FZB were able to confirm the findings in innovative, human mucous membrane models.
“Our data show that the combination of the two messenger substances TNFα and TGFβ severely disrupts the regeneration of the ciliated epithelium,” explains Reddy. “The persistent inflammation in the nasal mucosa is not maintained by the virus itself, but is driven by these messenger substances,” Reddy continued. The respiratory mucosa cannot therefore maintain its defensive function, which can result in long-lasting respiratory problems and increased susceptibility to infections, which are typical of PCS.
Results provide possible therapeutic targets
The results of the study could provide new starting points for the targeted treatment of post-COVID syndrome. “Our observations point to specific signaling pathways that apparently play a crucial role in PCS. These could be influenced therapeutically in order to alleviate the symptoms and possibly prevent long-term damage to the nasal mucosa,” explains lead author Fähnrich. The observed mechanisms could even play a role in other chronic lung diseases, which needs to be examined in more detail in further studies.
The study is an example of successful interdisciplinary and translational research within the PMI Cluster of Excellence. The close cooperation between the FZB, the LIED at the University of Lübeck and the University Hospital Schleswig-Holstein (UKSH), as well as the industrial partner Singleron, was crucial to the success. Only through this close cooperation could high-quality single cell data be collected and evaluated using modern bioinformatics methods.
