Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed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. Hamdi, H.; Abdaldayem, E. The human-COVID-19 Tango: Connecting the Dots. Preprints 2020, 2020040160.


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.


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


Biology and Life Sciences, Virology

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.
+ Respond to this comment
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
+ Respond to this comment
Comment 3
Received: 16 April 2020
Commenter: Julia Driessen
The commenter has declared there is no conflict of interests.
Comment: Dear dr. Hamdi and dr. Abdaldayem,

Thank you for this very interesting review on the interaction of RAS and COVID-19.

Could you comment on the prevalence of COVID19 among young adults without any medical history, who are often athletes, and still can get very ill from COVID19?
Would it be possible that due to high excercise/training, the angiotensin II levels are lower in these people, which would sensitize them for COVID19 due to less competition with the ACE2 receptor?

Many thanks in advance,

Best regards,
Julia Driessen
+ Respond to this comment

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 2
Metrics 0

Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.