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Other important proteins involved in this process include disintegrin and metalloproteinase domain\u2010containing protein 17 (ADAM17) also known as tumour necrosis factor\u2010\u03b1\u2010converting enzyme and transmembrane serine protease 2. ACE2 converts angiotensin II (Ang II) to angiotensin (1\u20137), to balance the renin angiotensin system. Membrane\u2010bound ACE2 ectodomain shedding is mediated by ADAM17 upon viral spike binding, Ang II overproduction and in several diseases. The shed soluble ACE2 (sACE2) retains its catalytic activity, but its precise role in viral entry is still unclear. Therapeutic sACE2 is claimed to exert dual effects; reduction of excess Ang II and blocking viral entry by masking the spike protein. Nevertheless, the paradox is why SARS\u2010CoV\u20102 comorbid patients struggle to attain such benefit in viral infection despite having a high amount of sACE2. In this review, we discuss the possible detrimental role of sACE2 and speculate on a series of events where protease primed or non\u2010primed virus\u2013sACE2 complex might enter the host cell. As extracellular virus can bind many sACE2 molecules, sACE2 level could be reduced drastically upon endocytosis by the host cell. A consequential rapid rise in Ang II level could potentially aggravate disease severity through Ang II\u2010angiotensin II receptor type 1 (AT1R) axis in comorbid patients. Hence, monitoring sACE2 and Ang II level in coronavirus disease 2019 comorbid patients are crucial to ensure safe and efficient intervention using therapeutic sACE2 and vaccines.<\/jats:p>","DOI":"10.1002\/rmv.2213","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T04:00:34Z","timestamp":1610683234000},"page":"1-12","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Potential detrimental role of soluble ACE2 in severe COVID\u201019 comorbid patients"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1211-8642","authenticated-orcid":false,"given":"Mohammad Mahmudur","family":"Rahman","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology Bangladesh University of Health Sciences  Dhaka 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