Preprint Review Version 2 This version is not peer-reviewed

The human-COVID-19 Tango: Connecting the Dots

Version 1 : Received: 8 April 2020 / Approved: 9 April 2020 / Online: 9 April 2020 (14:48:21 CEST)
Version 2 : Received: 13 April 2020 / Approved: 14 April 2020 / Online: 14 April 2020 (14:34:43 CEST)

How to cite: Hamdi, H.; Abdaldayem, E. The human-COVID-19 Tango: Connecting the Dots. Preprints 2020, 2020040160 (doi: 10.20944/preprints202004.0160.v2). Hamdi, H.; Abdaldayem, E. The human-COVID-19 Tango: Connecting the Dots. Preprints 2020, 2020040160 (doi: 10.20944/preprints202004.0160.v2).


As the world grapples with a pandemic with various and expanding epicenters, a flurry of medical and scientific activity has gained speed and momentum in a race to halt COVID-19. A controversial topic has been the connection between COVID-19 and the Renin-Angiotensin system (RAS). COVID-19, like Sars before it, enters by way of the Angiotensin Converting Enzyme 2 (ACE2). ACE2 is ubiquitously expressed in many tissues in the body serving as the doorway by which the virus can enter and spread causing inflammatory havoc. Demographic evidence coming out of China and other locations make it clear that the elderly and those suffering cardiovascular complications such as hypertension etc are most at risk. The connection to RAS and the demographic nature of the data coming out has led many to advance hypothesis, recommendations and even therapies based on existing RAS inhibitors and other components of the renin-Angiotensin system. It is pertinent to review the literature in the context of our understanding of the renin-angiotesnin system to allow better judgements to be made as well as lines of research initiated advancing a quick resolution to COVID-19. Covid-19 appears invincible as if dipped in the river Styx, but even Achilles had a vulnerable heel. Understanding the homeostatic balance that the coronavirus disrupts, we can discover the arrow in corona’s heel.

Subject Areas

COVID-19; ACE; ACE2; Angiotensin II; Bradykinin; RAS inhibitors; ACE inhibitors; AT1 receptor blockers; Losartan; Bradykinin Antagonists; Ang II loading; Giapreza; Icatibant.

Comments (2)

Comment 1
Received: 14 April 2020
Commenter: Hamdi Hamdi
Commenter's Conflict of Interests: Author
Comment: Grammatical mistakes and spelling errors were corrected. Extraneous words were removed. Figures were added to the manuscript for clarity of the ideas contained in the text. The word Covid in the title was replaced by Covid-19. All protein names were capitalized.
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Comment 2
Received: 14 April 2020
Commenter: Hawazen Hirbawi
The commenter has declared there is no conflict of interests.
Comment: The explanation provided for why children tend to have a mild COVID-19 infection while adults have a virulent infection is scientifically sound. This is a logical argument, which should be immediately considered by the medical community. The contrast made between the renin-angiotensin system in adults and children in the context of COVID-19 is brilliant! I really like this new version of the paper. The diagrams are very helpful indeed. I hope many in my profession can read this paper.

Hawazen Hirbawi, MD
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