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Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) infects the host by binding to angiotensin\u2010converting enzyme 2 (ACE2). The role of ACE2 in the pathophysiology of coronavirus disease 2019 (COVID\u201019) is a topic of debate, with clinical and experimental evidence indicating a multifaceted relationship between ACE2 activity and disease severity. Here, we review the mechanisms by which the peptidergic substrates and products of ACE and ACE2 contribute to physiological and pathophysiological processes and hypothesise how down\u2010regulation of ACE2 by SARS\u2010CoV\u20102 cellular entry disrupts homeostasis. A better understanding of the endocrinology of the disease, in particular the neuroendocrinology of ACE2 during COVID\u201019, may contribute to the timely design of new therapeutic strategies, including the regulation of ACE2 itself by steroid hormones, to ameliorate the severity of COVID\u201019.<\/jats:p>","DOI":"10.1111\/jne.12935","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T01:44:52Z","timestamp":1611020692000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["ACE2 in the second act of COVID\u201019 syndrome: Peptide dysregulation and possible correction with oestrogen"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7422-5136","authenticated-orcid":false,"given":"Limei","family":"Zhang","sequence":"first","affiliation":[{"name":"Dept. 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