# Airway Basal Stem Cells Inflammatory Alterations in COVID‐19 and Mitigation by Mesenchymal Stem Cells

## TL;DR

This study shows that airway stem cells from COVID-19 patients show harmful changes, but mesenchymal stem cells can reduce these effects.

## Contribution

This is the first study to isolate airway basal stem cells from Chinese COVID-19 patients and test mesenchymal stem cell co-culture effects.

## Key findings

- Airway basal stem cells from COVID-19 patients show goblet cell hyperplasia, inflammation, and fibrosis.
- Mesenchymal stem cell co-culture reduces these harmful effects via interferon signaling modulation.
- The study establishes a new xenograft model for studying airway stem cell alterations in COVID-19.

## Abstract

SARS‐CoV‐2 infection and the resultant COVID‐19 pneumonia cause significant damage to the airway and lung epithelium. This damage manifests as mucus hypersecretion, pulmonary inflammation and fibrosis, which often lead to long‐term complications collectively referred to as long COVID or post‐acute sequelae of COVID‐19 (PASC). The airway epithelium, as the first line of defence against respiratory pathogens, depends on airway basal stem cells (BSCs) for regeneration. Alterations in BSCs are associated with impaired epithelial repair and may contribute to the respiratory complications observed in PASC. Given the critical role of BSCs in maintaining epithelial integrity, understanding their alterations in COVID‐19 is essential for developing effective therapeutic strategies. This study investigates the intrinsic properties of BSCs derived from COVID‐19 patients and evaluates the modulatory effects of mesenchymal stem cells (MSCs). Through a combination of functional assessments and transcriptomic profiling, we identified key phenotypic and molecular deviations in COVID‐19 patient‐derived BSCs, including goblet cell hyperplasia, inflammation and fibrosis, which may underlie their contribution to PASC. Notably, MSC co‐culture significantly mitigated these adverse effects, potentially through modulation of the interferon signalling pathway. This is the first study to isolate BSCs from COVID‐19 patients in the Chinese population and establish a COVID‐19 BSC‐based xenograft model. Our findings reveal critical insights into the role of BSCs in epithelial repair and their inflammatory alterations in COVID‐19 pathology, with potential relevance to PASC and virus‐induced respiratory sequelae. Additionally, our study highlights MSC‐based therapies as a promising strategy to address respiratory sequelae and persistent symptoms.

Airway basal stem cells derived from COVID‐19 patients demonstrated pronounced goblet cell hyperplasia, inflammatory responses and tendencies toward fibrosis. Co‐culture with mesenchymal stem cells (MSCs) notably reduced these pathological changes, likely due to MSCs' regulatory effects on the interferon signalling pathway.