key: cord-0910559-jmo38w7g
authors: McGonagle, Dennis; Bridgewood, Charlie; Ramanan, Athimalaipet V; Meaney, James F M; Watad, Abdulla
title: COVID-19: angiotensin II in development of lung immunothrombosis and vasculitis mimics – Author's reply
date: 2021-03-17
journal: Lancet Rheumatol
DOI: 10.1016/s2665-9913(21)00065-5
sha: 2c7d554016ca10fc1dfa1dac57cbb7e281c5d012
doc_id: 910559
cord_uid: jmo38w7g

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In our Viewpoint, we mentioned several mechanisms, including pulmonary microembolisation, systemic RNAaemia with arteriolar and venous thrombosis, and other factors contributing to the thrombotic phenotypes that can mimic vasculitis. The authors point out that angiotensin II might play a role in this immunothrombotic process, and they point to one animal model in particular in which angiotensin II was implicated and associated with accelerated arteriolar thrombus formation and leukocyte recruitment in venules. Thus, the authors propose that, after the initial viral-angiotensin-converting enzyme 2 (ACE2) receptor interaction, increased angiotensin II concentrations can further trigger endothelial inflammation and more extensive in situ immunothrombosis.

Of course, there are several other studies incriminating ACE2 in cardiovascular physiology, and a multiplicity of mechanisms conse quent to its dysregulation might facilitate viral entry into cells and also concomitantly block generation of the anti-inflammatory angiotensin-(1-7). 2 Indeed, following this line of enquiry, a recent small study showed that recombinant ACE2 reduces systemic concentrations of angiotensin II in patients with severe COVID-19, with a hint that this might be a helpful therapeutic strategy. 3 Further studies will clarify this approach, but we believe that the predominant mechanism of pulmonary intravascular coagulopathy 4 is likely to be due to immunothrombosis resulting from the juxtaposition of the large alveolar and capillary surface areas in the context of severe viral pneumonia, and it is the SARS-CoV-2 tropism for ACE2 on pneumocytes, rather than the systemic factors suggested by Lloyd-Jones and Oudkerk, that determines the outcome of severe infection. Further clinical trials will clarify this.

COVID-19 vasculitis and novel vasculitis mimics

COVID-19 infection, inflammation, and coagulopathy: missing pieces in the puzzle

A pilot clinical trial of recombinant human angiotensinconverting enzyme 2 in acute respiratory distress syndrome

Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia