Damaged skin: a potential transmission route for SARS-CoV-2?

In different skin models, key receptors could be identified whose modulation can help in creating compromised-skin topicals against SARS-CoV-2 entry.

Genetic polymorphisms in the androgen receptor associated with more or less severe COVID-19

The entry of SARS-CoV-2 virus in host cells depends on the availability of virus receptors and entry cofactors on the surface of host cells. The most important receptors identified so far are the angiotensin-converting enzyme 2 (ACE2) receptor, the transmembrane serine protease 2 (TMPRSS2), and the neuropilin-1 (NRP-1).

All receptors mentioned above are under the control of androgen receptor. Previously, it has been shown that genetic polymorphisms in the androgen receptor are associated with either more or less severe COVID-19 disease, stressing the importance of this receptor for the outcome of the disease2

Recommended hygiene procedures to prevent the spread of SARS-CoV-2 include repeated handwashing and frequent use of hand sanitisers. Both can disrupt skin barrier integrity leading to damaged skin that may contribute to an increased viral transmission.

To assess whether damaged skin could represent a potential gateway for SARS-Cov-2, Dr Hanan Osman-Ponchet (PKDERM, Antibes, France) and her team measured the expression levels of SARS-CoV-2 receptors in different human in-vitro skin models (i.e. fibroblast- and keratinocyte cultures, 3D skin model, and skin explants), and evaluated the effect of dexamethasone on mRNA expression level of SARS-CoV-2 receptors in in-vitro skin models. “The ultimate goal was to choose the most suitable skin model for the further investigation of a possible skin transmission of SARS-Cov-2,“ Dr Osman-Ponchet explained.

In contrast to lung models, androgen receptor was well expressed in skin models

The results showed that ACE2 and TMPRSS2 receptors are well expressed in skin models, especially in 3D-skin models and skin explants. The level of expression is lower than in a commonly used lung model. Moreover, the expression level of NRP-1 was similar in skin and lung models. In contrast to lung models, androgen receptor was well expressed in skin models (both in fibroblast cultures and skin explant). 

In a second step, the researchers assessed the effect of dexamethasone treatment on the skin models. When keratinocytes were treated with dexamethasone, both IL-8 production in lipopolysaccharides and expression of ACE2 was markedly reduced, an effect that could also be demonstrated in the 3D skin model. “These results show us that IL-8 and ACE2 expression in skin can be modulated,” Dr Osman-Ponchet said.

The fact that SARS-CoV-2 key receptors are expressed in the skin indicates that skin might represent a potential entry route, especially when it is damaged. A future trial will assess a new damaged skin model to develop potential protective means against this route of entry.

References
  1. Osman-Ponchet H, et al. Is compromised skin a potential transmission route for SARS-CoV-2? D3T01.2D, EADV Congress 2021, 29 Sept–2 Oct.
  2. Baldassarri M, et al. EBioMedicine 2021;65:103246.