Journal
JOURNAL OF DERMATOLOGY
Volume 50, Issue 8, Pages 1052-1057Publisher
WILEY
DOI: 10.1111/1346-8138.16793
Keywords
COVID-19; maculopapular viral rash; SARS-CoV-2; single-cell RNA sequencing
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This study conducted single-cell RNA sequencing analysis on a COVID-19 patient with a skin rash. The results show the expression of ACE2 and TMPRSS2, the entry receptors for SARS-CoV-2, in the patient's keratinocytes, indicating profound transcriptional changes in these cells. Inflammatory immune cells also exhibited characteristics of immune response. These findings are important for understanding SARS-CoV-2-associated skin conditions.
Coronavirus disease 2019 (COVID-19) primarily affects the respiratory system but extrapulmonary manifestations, including the skin, have been well documented. However, transcriptomic profiles of skin lesions have not been performed thus far. Here, we present a single-cell RNA sequencing analysis in a patient with COVID-19 infection with a maculopapular skin rash while on treatment with the interleukin (IL)-12/IL-23 blocker ustekinumab for his underlying psoriasis. Results were compared with healthy controls and untreated psoriasis lesions. We found the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry receptors ACE2 and TMPRSS2 in keratinocytes of the patient with COVID-19, while ACE2 expression was low to undetectable in psoriasis lesions and healthy skin. Among all cell types, ACE2+ keratinocyte clusters showed the highest levels of transcriptomic dysregulation in COVID-19, expressing type 1-associated immune markers such as CXCL9 and CXCL10. In line with a generally type 1-skewed immune microenvironment, cytotoxic lymphocytes showed increased expression of the IFNG gene and other T-cell effector genes, while type 2, type 17, or type 22 T-cell activation was largely absent. Conversely, downregulation of several anti-inflammatory mediators was observed. This first transcriptomic description of a COVID-19-associated rash identifies ACE2+ keratinocytes displaying profound transcriptional changes, and inflammatory immune cells that might help to improve the understanding of SARS-CoV-2-associated skin conditions.
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