Heightened Innate Immune and Inflammatory Gene Expression in the Skin of Severe COVID-19 Cases

Cutaneous manifestations of SARS-CoV-2 infection exhibit significant variability, yet the role of innate immune responses in the skin of COVID-19 patients remains poorly understood. In this study, we investigated the transcriptomic profile of skin samples from patients who succumbed to COVID-19.

Skin autopsies from COVID-19 patients with post-mortem time of less than 20 hours were obtained from University of São Paulo Medical School Hospital and healthy skin samples, were submitted to RNA sequencing analysis. Validation of differentially expressed genes (DEGs) was performed by real-Time PCR.

Our analysis revealed markedly elevated expression of type I interferon (IFN)-inducible antiviral factors, antioxidant enzymes, and components of several cytokine-signaling pathways in COVID-19 skin samples compared to healthy controls. SARS-CoV-2 infection robustly induced numerous interferon-stimulated genes (ISGs), IFITs, IRF, S100 family with a notable enrichment of those associated with antiviral and inflammatory responses. Moreover, the presence of counter-regulatory factors such as SOCS3 and NFKBIA indicate the involvement of anti-inflammatory mechanisms in the skin. Furthermore, deconvolution data indicated increased presence of macrophages other nucleated cells in vessels in the skin of COVID-19 patients, highlighting the involvement of innate immune mechanisms.

The results revealed cutaneous alterations in the expression of genes associated with innate immunity and inflammation factors. This suggests that, unlike tissues with viral tropism, the skin is enriched with antiviral factors to defend against SARS-CoV-2. This information could be useful for developing specific antiviral therapies.