Skin as a Potential Entry Point for SARS-CoV-2 Virus.

Area of Science:

• Dermatology
• Virology
• Immunology

Background:

• SARS-CoV-2 primarily infects the respiratory tract, but skin lesions are common in COVID-19 patients.
• Pre-existing inflammatory skin conditions like psoriasis and atopic dermatitis (AD) increase COVID-19 risk.
• The role of skin in SARS-CoV-2 infection requires further investigation.

Purpose of the Study:

• To investigate if skin inflammation enhances SARS-CoV-2 entry.
• To evaluate the expression of viral entry receptors (ACE2, TMPRSS2) in inflamed skin models.
• To assess the impact of inflammatory cytokines on viral transduction in skin.

Main Methods:

• Utilized 3D human skin organoids (HSO) and neonatal skin explants.
• Treated HSO with individual and combined cytokines (TNF-α, IL-6, IL-1β, IFN-γ) and Th1/Th2 cocktails.
• Applied Spike-pseudotyped lentiviral reporter to assess viral entry into control and treated skin models.
• Performed transcriptomic analysis to compare gene expression in inflamed skin and COVID-19 lung tissue.

Main Results:

• Cytokine treatment, particularly combinations and Th1 cocktail, upregulated ACE2 and TMPRSS2 mRNA/protein levels in HSO.
• Spike-pseudotyped lentiviral reporter successfully transduced cytokine-treated HSO and skin explants.
• Inflamed skin models showed significantly increased viral entry compared to controls.
• Gene expression signatures in inflamed skin partially overlapped with those in COVID-19 lung tissue.

Conclusions:

• Skin inflammation can transiently increase human skin's permissiveness to SARS-CoV-2 entry.
• ACE2 and TMPRSS2 upregulation in inflamed skin facilitates viral entry.
• The skin may represent an underappreciated interface for SARS-CoV-2 host interactions.