Background 

Upregulation of epithelial damage markers in the airways can be seen even several months after acute COVID-19, but whether this is associated with abnormal epithelial function is not known.

Aims

To evaluate pulmonary epithelial responses to mechanical or viral injury in patients post COVID-19.

Methods

Functional capacity of bronchial epithelial cells from 15 donors previously hospitalised for COVID-19 was evaluated in comparison to those derived from healthy volunteers. Acquisition of epithelial cells was performed at a median of 171(IQR 121-179) days post hospital discharge. The cohort consisted of 12/15 (75%) males with a median age of 58 (52?70) years.

Wound healing response to a scratch assay was assessed in submerged culture, and an in vitro influenza challenge model devised to evaluate epithelial responses to viral injury in cells cultured at air-liquid interface.

Results

Wound healing at 24 hours was impaired post COVID-19 compared to healthy controls (74.8% +/-5.6 vs 96.5% +/-1.5 wound closure), but cellular proliferation was comparable between groups (1.23 vs 1.33-fold change from baseline). Heterogeneity in wound closure was seen post-COVID-19, but this was unrelated to time from hospital admission (p=0.32), age (p=0.64), severity of the acute illness (p=0.17) and extent of residual abnormality on CT (p=0.39). However, inflammatory and interferon responses to influenza infection were similar between the groups, with peak response occurring at 72 hours post infection.

Conclusion

Impairment in epithelial repair mechanisms may be present, even several months after acute COVID-19. However, epithelial responses to a viral challenge appear preserved. Further studies evaluating the mechanisms underlying this aberrant response are ongoing.