key: cord-0725229-5xh4p786
authors: Tanabe, Naoya; Matsumoto, Hisako; Hamada, Satoshi; Ito, Isao; Hirai, Toyohiro
title: Dupilumab maintenance therapy in an asthmatic patient with coronavirus disease 2019 pneumonia
date: 2020-11-07
journal: Allergol Int
DOI: 10.1016/j.alit.2020.10.005
sha: 7fc41609c21344110dba870f0308b91fce341ce9
doc_id: 725229
cord_uid: 5xh4p786

nan

HM received honoraria from Sanofi outside the submitted work. SH reports 25 grants from Teijin Pharma, outside the submitted work. The rest of the authors 26 have no conflict of interest. Dupilumab is a human monoclonal antibody against the alfa subunit of 31 interleukin (IL)-4 receptor that regulates type2 inflammation by inhibiting 32 signaling from IL-4 and IL-13. Dupilumab is widely used as an important biologic 33 agent to control severe condition of asthma, eosinophilic chronic rhinosinusitis, 34 and atopic dermatitis. In the pandemic of severe acute respiratory 35 syndrome-coronavirus-2 (SARS-CoV-2) and its associated respiratory disease, clinical course is summarized in Figure 1 . He was asymptomatic, but diagnosed 47 as COVID-19 (day1). He was admitted to the hospital for close monitoring on 48 J o u r n a l P r e -p r o o f day 3, but had a fever (38.3°C) and oral favipiravir was started on day 6. No 49 respiratory symptoms had been reported until he rapidly developed dyspnea and 50 hypoxemia and nasal oxygen therapy was started on day 11. On day12, chest 51 computed tomography (CT) showed bilateral peripheral-dominant ground glass 52 opacity (GGO) and consolidation ( Fig. 2A) , and because he had several risk 53 factors for severe COVID-19 including obesity and diabetes, he was transferred 54 to intensive care unit at our hospital and received oxygen therapy via face mask 55 (5-6 L/min).

At the transfer (day12), there were no signs of any exacerbation of 57 asthma. In addition to regular inhalation of relvar ellipta ® 200 µg/day, inhaled 58 ciclesonide 800 µg/day was started, which has been suggested for anti-viral 59 effect in small case series [1]. Moreover, intravenous administration of 60 dexamethasone 6.6 mg/day and heparin was started. On day 14, favipiravir was 61 switched to remdesivir. He was gradually recovered, a negative PCR for 62 SARS-CoV-2 was confirmed on day 27, oxygen therapy was discontinued on 63 day 28. Follow-up chest CT was performed on day 31. Bilateral GGO was 64 resolved and partially converted to consolidation (Fig. 2B) . He was discharged 65 on day 34.

He was a never smoker and diagnosed as asthma at early 40s with 67 higher blood eosinophil (10-20% of total white blood cells). He had been treated 68 with relvar ellipta ® 200 µg/day and mepolizumab for two years, but developed 69 pruritus cutaneus while asthma control was maintained. Then, mepolizumab Dupilumab is an essential biologic agent for severe type of asthma, 84 eosinophilic chronic rhinosinusitis, and atopic dermatitis. As well as other 85 biologics, there is a concern whether dupilumab can be used safely in the era of 86 COVID-19 pandemic. One of the concerns may stem from its potential 87 modulation of angiotensin-converting enzyme 2 (ACE2) expression. In initial 88 infection of SARS-Cov-2, the spike protein of inhaled virus binds to ACE2 89 located on lung epithelium membrane. Then, the virus is incorporated into the 90 host epithelium such as alveolar type-2 epithelial cells. This process depends on 91 cellular serine protease, termed transmembrane protease serine 2 (TMPRSS2). 

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