SARS-CoV-2 spike treatment and transfection impairs airway epithelial repair

The airway epithelium serves as a physical and immune barrier against inhaled insults. This tissue is susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and, following injury, the airway epithelium undergoes repair to restore barrier function. Although components of SARS-CoV-2, such as the spike glycoprotein essential in viral entry, have been shown to alter biological functions in various tissues, it is unclear how SARS-CoV-2 can impact airway epithelial functions, such as wound repair.

In this study, 16HBE14o- epithelial monolayer cultures were either treated with recombinant SARS-CoV-2 spike glycoprotein S1 subunit at 4 μg·mL^-1 or transfected with a plasmid expressing full-length spike glycoprotein. Secreted inflammatory mediators, markers of proliferation and cell cycle arrest, culture proliferation, and wound closure measurements following mechanical injury were assessed.

Spike treatment and transfection altered measures of culture proliferation and markers of proliferation and cell cycle arrest. Secreted interleukin-6 but not interleukin-8 were significantly higher with spike S1 treatment, while both were significantly elevated with spike transfection. Wound closure was inhibited by both spike treatment and transfection, with significant reductions compared to control.

SARS-CoV-2 spike S1 treatment and transfection can alter measures of proliferation and inflammation as well as impair wound closure of 16HBE14o- airway epithelial cells. These results highlight how components of SARS-CoV-2 can impair functions of the airway epithelium independent of viral replication.