Single‐cell RNA sequencing analysis of a COVID‐19–associated maculopapular rash in a patient with psoriasis treated with ustekinumab

Abstract

AbstractCoronavirus 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.