Associations between COVID-19 and skin conditions identified through epidemiology and genomic studies

Patrick, Matthew T.; Zhang, Haihan; Wasikowski, Rachael; Prens, Errol P.; Weidinger, Stephan; Gudjonsson, Johann E.; Elder, James T.; He, Kevin; Tsoi, Lam C.

Background COVID-19 is commonly associated with skin manifestations, and may also exacerbate existing skin diseases, yet the relationship between COVID-19 and skin diseases remains unclear. Objective By investigating this relationship through a multi-omics approach, we sought to ascertain whether patients with skin conditions are more susceptible to COVID-19. Methods We conducted an epidemiological study and then compared gene expression across nine different inflammatory skin conditions and SARS-CoV-2 infected bronchial epithelial cell lines, then performed a GWAS trans-disease meta-analysis between COVID-19 susceptibility and two skin diseases (psoriasis and atopic dermatitis). Results Skin conditions, including psoriasis and atopic dermatitis, increase the risk of COVID-19 (OR=1.55, p=1.4x10 -9 ), but decrease the risk of mechanical ventilation (OR=0.22, p=8.5x10 -5 ). We observed significant overlap in gene expression between the infected normal bronchial epithelial cells (NHBE) and inflammatory skin diseases, such as psoriasis, and atopic dermatitis. For genes that are commonly induced in both the SARS-CoV-2 infection and skin diseases, there are four S100 family members located in the epidermal differentiation complex (EDC), and we also identified the ‘IL-17 signaling pathway’ (p=4.9x10 -77 ) as one of the most significantly enriched pathways. Furthermore, a shared genome-wide significant locus in the epidermal differentiation complex (EDC) was identified between psoriasis and SARS-CoV-2 infection, with the lead marker being a significant eQTL for S100A12 (p=3.3x10 -7 ). Conclusion Together our findings suggest association between inflammatory skin conditions and higher risk of COVID-19, but with less severe course, and highlight shared components involved in anti-COVID19 immune response.