Associations between COVID-19 and skin conditions identified through epidemiology and genomic studies - 04/03/21
, Haihan Zhang, MS b, Rachael Wasikowski, MS a, Errol P. Prens, MD, PhD c, Stephan Weidinger, MD, PhD d, Johann E. Gudjonsson, MD, PhD a, James T. Elder, MD, PhD a, e, Kevin He, PhD b, Lam C. Tsoi, PhD a, b, f, ⁎
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Abstract |
Background |
Coronavirus disease 2019 (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 multiomics 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 9 different inflammatory skin conditions and severe acute respiratory syndrome coronavirus 2–infected bronchial epithelial cell lines, and then performed a genome-wide association study transdisease meta-analysis between COVID-19 susceptibility and 2 skin diseases (psoriasis and atopic dermatitis).
Results |
Skin conditions, including psoriasis and atopic dermatitis, increase the risk of COVID-19 (odds ratio, 1.55; P = 1.4 × 10−9) but decrease the risk of mechanical ventilation (odds ratio, 0.22; P = 8.5 × 10−5). We observed significant overlap in gene expression between the infected normal bronchial epithelial cells and inflammatory skin diseases, such as psoriasis and atopic dermatitis. For genes that are commonly induced in both the severe acute respiratory syndrome coronavirus 2 infection and skin diseases, there are 4 S100 family members located in the epidermal differentiation complex, and we also identified the “IL-17 signaling pathway” (P = 4.9 × 10−77) as one of the most significantly enriched pathways. Furthermore, a shared genome-wide significant locus in the epidermal differentiation complex was identified between psoriasis and severe acute respiratory syndrome coronavirus 2 infection, with the lead marker being a significant expression quantitative trait locus for S100A12 (P = 3.3 × 10−7).
Conclusions |
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–COVID-19 immune response.
Il testo completo di questo articolo è disponibile in PDF.Key words : COVID-19, SARS-CoV-2, skin conditions, psoriasis, atopic dermatitis, epidemiology, genetics, gene expression
Abbreviations used : ACE2, ASSET, BMI, CDC, COPD, COVID-19, FC, FDR, GTEx, hBO, HISAT2, NHBE, OR, SARS-CoV-2, SLE, TDMA
Mappa
| This work was supported by the Arthritis National Research Foundation and the National Psoriasis Foundation (L.C.T. and M.T.P.), National Psoriasis Foundation’s Psoriasis Prevention Initiative (L.C.T. and J.E.G.), and awards from the National Institutes of Health (grant nos. R01AR042742, R01AR050511, R01AR054966, R01AR063611, and R01AR065183 to J.T.E. and grant no. K01AR072129 to L.C.T.). L.C.T. was also supported by the Dermatology Foundation, and M.T.P. was supported by a Precision Health Scholars Award from the University of Michigan. L.C.T., J.E.G., and J.T.E. are supported by the Dawn and Dudley Holmes Foundation and the Babcock Memorial Trust. J.E.G. was supported by the National Institutes of Health (grant nos. K08AR060802 and R01AR06907) and the Taubman Medical Research Institute as the Frances and Kenneth Eisenberg Emerging Scholar. L.C.T. and J.E.G. are also supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; grant no. UM-SBDRC 1P30AR075043) and the Taubman Institute Innovation Project. J.T.E. is supported by the Ann Arbor Veterans Affairs Hospital. |
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| Disclosure of potential conflict of interest: S. Weidinger is coprincipal investigator of the German Atopic Eczema Registry TREATgermany; has received institutional research grants from Sanofi Deutschland GmbH, Leo Pharma, and La Roche Posay; has performed consultancies for Sanofi-Genzyme, Regeneron, LEO Pharma, AbbVie, Pfizer, Eli Lilly, Kymab, and Novartis; has also lectured at educational events sponsored by Sanofi-Genzyme, Regeneron, LEO Pharma, AbbVie, Novartis, and Galderma; and is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of psoriasis and atopic eczema. J. E. Gudjonsson received research grants from Almirall, Eli Lilly, Kyowa Kirin, and SunPharma, and serves as advisory board member for Novartis, Eli Lilly, Almirall, and AnaptysBio. The rest of the authors declare that they have no relevant conflicts of interest. |
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| Ethics statement: All human subjects provided written informed consent and were enrolled according to the protocols approved by the institutional review board for human subject research of each institution, in adherence with the Declaration of Helsinki principles. |
Vol 147 - N° 3
P. 857 - Marzo 2021 Ritorno al numero
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