Human recombinant soluble ACE2 in severe COVID 19

Angiotensin converting enzyme 2 (ACE2) is the crucial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor and protects multiple tissues, including the lung, from injury as a regulator of the renin–angiotensin system.1Bourgonje AR Abdulle AE Timens W et al.Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19).J Pathol. 2020; 251: 228-248Crossref Scopus (27) Google Scholar Therefore, ACE2 has become the focus of COVID-19 research and a plethora of drug development efforts. Among the novel compounds under development is human recombinant soluble ACE2 (hrsACE2 [APN01; Apeiron Biologics, Vienna, Austria]), which has two mechanisms of action that theoretically should be of benefit in COVID-19.2Zhang H Penninger JM Li Y Zhong N Slutsky AS Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target.Intensive Care Med. 2020; 46: 586-590Crossref PubMed Scopus (390) Google Scholar The first involves binding the viral spike protein and thereby neutralising SARS-CoV-2,3Monteil V Kwon H Prado P et al.Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2.Cell. 2020; 181: 905-913Summary Full Text Full Text PDF PubMed Scopus (224) Google Scholar and the second is minimising injury to multiple organs, including the lungs, kidneys, and heart, because of unabated renin–angiotensin system hyperactivation and increased angiotensin II concentrations.4Kuba K Imai Y Rao S et al.A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury.Nat Med. 2005; 11: 875-879Crossref PubMed Scopus (863) Google Scholar, 5Crackower MA Sarao R Oudit GY et al.Angiotensin-converting enzyme 2 is an essential regulator of heart function.Nature. 2002; 417: 822-828Crossref PubMed Scopus (985) Google Scholar, 6Wong DW Oudit GY Reich H et al.Loss of angiotensin-converting enzyme-2 (Ace2) accelerates diabetic kidney injury.Am J Pathol. 2007; 171: 438-451Summary Full Text Full Text PDF PubMed Scopus (172) Google Scholar hrsACE2 has been tested in 89 patients, namely in healthy volunteers in phase 1 studies and in patients with acute respiratory distress syndrome (ARDS) in phase 2 clinical studies, with a good safety profile.7Haschke M Schuster M Poglitsch M et al.Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects.Clin Pharmacokinet. 2013; 52: 783-792Crossref PubMed Scopus (96) Google Scholar, 8Khan A Benthin C Zeno B et al.A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome.Crit Care. 2017; 21: 234Crossref PubMed Scopus (149) Google Scholar Moreover, hrsACE2 can reduce SARS-CoV-2 load by a factor of 1000–5000 in in-vitro cell-culture experiments and engineered organoids, directly demonstrating that ACE2 can effectively neutralise SARS-CoV-2.3Monteil V Kwon H Prado P et al.Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2.Cell. 2020; 181: 905-913Summary Full Text Full Text PDF PubMed Scopus (224) Google Scholar We describe in this Case Report the first course of treatment with hrsACE2 of a patient with severe COVID-19.