Single-cell RNA sequencing analysis of a COVID-19-associated maculopapular rash in a patient with psoriasis treated with ustekinumab.
Katharina RindlerPhilipp TschandlJasmine P LevineLisa E ShawWolfgang WeningerMatthias FarlikConstanze JonakPatrick M BrunnerPublished in: The Journal of dermatology (2023)
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.
Keyphrases
- sars cov
- single cell
- respiratory syndrome coronavirus
- coronavirus disease
- rna seq
- wound healing
- high throughput
- angiotensin converting enzyme
- soft tissue
- angiotensin ii
- stem cells
- case report
- poor prognosis
- genome wide
- anti inflammatory
- cell proliferation
- immune response
- gene expression
- regulatory t cells
- dna methylation
- intellectual disability
- signaling pathway
- dendritic cells
- atopic dermatitis
- long non coding rna
- binding protein