If skin is a potential host of SARS-CoV-2, IL-17 antibody could reduce the risk of COVID-19

Abstract

To the Editor: In the era of the coronavirus disease 2019 (COVID-19) pandemic, debates have emerged on whether biologics might increase the risk of contracting the disease.1Lebwohl M. Rivera-Oyola R. Murrell D.F. Should biologics for psoriasis be interrupted in the era of COVID-19?.J Am Acad Dermatol. 2020; 82: 1217-1218Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar Interleukin (IL) 17 is a biologic that is widely used in dermatology. There were reports that viral reactivation, although extremely low, could be detected during the use of IL-17 antibody (160 mg subcutaneously at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8).2Snast I. Atzmony L. Braun M. Hodak E. Pavlovsky L. Risk for hepatitis B and C virus reactivation in patients with psoriasis on biologic therapies: a retrospective cohort study and systematic review of the literature.J Am Acad Dermatol. 2017; 77: 88-97.e5Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar This led to concerns in using the IL-17 antibody because it was believed that it could make patients more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). When we read the article by Sun et al3Sun Y. Zhou R. Zhang H. et al.Skin is a potential host of SARS-CoV-2: a clinical, single-cell transcriptome-profiling and histological study.J Am Acad Dermatol. 2020; 83: 1755-1757Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar in a recently published issue, a question occurred to us: If skin is a target of SARS-CoV-2, what might be the consequence of using the IL-17 antibody? Angiotensin-converting enzyme 2 (ACE2) is the main entrance receptor for SARS-CoV-2. Its expression is associated with the risk of making the target tissue susceptible to infection by SARS-CoV-2. Therefore, downregulating the expression of ACE2 could decrease the risk of COVID-19. To evaluate the influence of IL-17 antibody on skin ACE2 expression, we randomly selected 5 psoriasis patients who were treated with IL-17 antibody (Taltz, Eli Lilly and Company, Indianapolis, IN). The skin lesions of these patients were biopsied on week 0 and week 8 and prepared for RNA sequencing. The skin ACE2 expression of patients who underwent the antibody therapy for 8 weeks (0.36 ± 0.10; n = 5) was downregulated compared with that at week 0 (1.24 ± 0.50; n = 5), when the IL-17 antibody treatment had just begun (P < .05, paired t test). To confirm the result, we also selected 3 patients to compare the skin ACE2 expression at weeks 0 and 8 with immunofluorescence. Immunofluorescence staining revealed that the fluorescence intensity of ACE2 was downregulated in the skin at week 8 (0.84 ± 0.26; n = 3) compared with that before the IL-17 antibody treatment (9.23 ± 2.33; n = 3; P < .05; unpaired t test). Hence, either the messenger RNA or protein of ACE2 obtained from psoriasis patients can reveal that IL-17 antibody treatment remarkably reduces ACE2 expression. Our above-mentioned work proves that IL-17 antibody treatment during the COVID-19 pandemic is not contraindicated. Elevated ACE2 expression and detection of SARS-CoV-2 in the skin4Colmenero I. Santonja C. Alonso-Riaño M. et al.SARS-CoV-2 endothelial infection causes COVID-19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases.Br J Dermatol. 2020; 183: 729-737Crossref PubMed Scopus (281) Google Scholar of COVID-19 patients implied skin was a potential host of SARS-CoV-2. After IL-17 antibody treatment, the skin ACE2 expression was downregulated, which meant IL-17 antibody could decrease the risk of COVID-19 through lessening the cells that could interact with SARS-CoV-2. Additionally, IL-17 antibody could reverse the deteriorated barrier and inflammatory status in the skin of psoriasis patients, which meant less microbe infection. Herein, the specific microbe could be SARS-CoV-2. To our knowledge, until now there has been no evidence that COVID-19 can be spread by contact with skin. However, SARS-CoV-2 could survive on skin for about 9 hours,5Hirose R. Ikegaya H. Naito Y. et al.Survival of SARS-CoV-2 and influenza virus on the human skin: importance of hand hygiene in COVID-19.Clin Infect Dis. 2020:ciaa1517; https://doi.org/10.1093/cid/ciaa1517Crossref PubMed Scopus (65) Google Scholar which indicates that it might be transmitted through skin in certain skin conditions such as psoriasis. Thus, whether IL-17 antibody could reduce the COVID-19 risk through reversing the inflammatory skin status with a deteriorated barrier and preventing SARS-CoV-2 transmission should be further discussed.