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[OHDSI COVID-19] Review on the effect of ACE inhibitors and Angiotensin Receptor Blockers on COVID-19 incidence and complication rate

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#10

Thanks @Nicole_Pratt for checking over the spreadsheet and for sharing the reference. I’m glad we already have most of their citations accounted for. My current understanding of the plan is that there will be estimation studies comparing ACEs and ARBs against other hypertension treatments. So I think it’s a good idea to include all hypertension treatments in the literature review as long as the paper is talking about their relationship with incidence and/or complications of viral disease.

Again, feel free to make revisions to the spreadsheet if you think it needs any. I think this literature review will include a diverse set of studies (e.g. cell studies, human studies) as well as commentaries and letters. I’m still thinking through what specific pieces of information / features we want to abstract from cellular studies, commentaries, etc.

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#11

Hey everyone. Just wanted to post a couple updates on the current progress.

  • If you see the Google Doc linked above you’ll see that the list of potentially relevant studies is growing pretty quickly. As was expressed in the statements by various academic societies this week, there is very little literature describing any sort of causal analyses (observational or randomized) of the relationship between antihypertensive medications and viral incidence / complications. However, over the past 12 hours, I’ve learned that there is an extensive history of possibly relevant cellular studies that describe how coronaviruses interact with the ACE-2 receptor, much of which relates to SARS-CoV and MERS-CoV.

  • Given the short turnaround we have for this literature review, I don’t want anyone getting lost trying to parse the cell studies. If you sign up to review one of those, do your best to document the main findings and conclusions. There are several commentaries on the list which have already done a nice job synthesizing the existing evidence from cellular studies on how caronaviruses bind with receptors in human (and animal) hosts. We will definitely need to lean heavily on those existing summaries in order to provide some meaningful synthesis of evidence by tomorrow night.

  • I’m going to switch gears right now away from searching and start reviewing some articles in more detail. Obviously if anyone finds any relevant citations that are not in the list, feel free to add them.

If anyone has any questions feel free to email me or reach out to me on Microsoft Teams (mconove1@its.jnj.com)

#12

There is another viewpoint out in JAMA, but probably no surprising finding/conclusion:
COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor BlockersWhat Is the Evidence?

#13

Thanks for posting @NKolb. It’s been added to the spreadsheet.

#14

Hey everyone - we’ve been making forward progress on populating the study abstraction sheet (thanks @Nicole_Pratt for all your work). As I’ve been populating the sheet, I’ve started drafting a rough outline of how to tie all of this information together (see Google Doc link below). This is still incomplete since it only includes the studies I abstracted. Hoping to work more on it this afternoon and tonight. In the meantime, anyone is welcome to add/delete/revise as much as they like.

https://drive.google.com/file/d/1XpXg6jv9MsI9jQ4ZzUDDlGeD_xd77osK/view?usp=sharing

#15

The studies that @Nicole_Pratt abstracted have now been incorporated into the write-up / outline (linked above).

#16

Hi everyone,

As posted by @CSung in Research questions that the OHDSI community can potentially answer to suport the COVID-19 response, there’s also a hypothesis that AT1R blockers / angiotensin 2 such as losartan or valsartan can have a beneficial/protective effect. Since these are common medicines for treatment of a.o. hypertension, there is a chance that we can see this effect in action if we can identify these subgroups. Is this something we can assess in the study-a-thon?

See https://doi.org/10.1002/ddr.21656 and there’s also a nice explainer video of the biochemistry which I have to look up,

Greetings,

Kees

#17

Hey @keesvanbochove . Thanks for sharing. The good news is that we have already incorporated the article you linked (Gurwitz et al. 2020) into the literature review spreadsheet and the text write-up / outline - both of those are linked above. Gurwitz et al is not the only one to propose mechanisms whereby ACEs and ARBs may have different effects on the SARS-CoV-2 cellular attachment process. So I agree with that there would be value to producing evidence that considers ACE’s and ARBs separately (instead of just a comparison of ACE/ARB vs. calcium-channel blockers).

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#18

Patrick and team,
Thank you for this important effort.

#19

Hey everyone,

We have now moved the two google docs above (the lit review spreadsheet and the lit review text write-up) over to the “Files” tab in the “Study-Estimation-Ace Inhibitors” Microsoft Teams channel (so the two google docs linked above are no longer active). If you want to collaborate/contribute and you are on the study-a-thon team, please find them there. If anyone has any trouble finding these documents please reach out to me on Teams or by email (mconove1@its.jnj.com)

A spreadsheet containing information abstracted from key references has been posted to the “Files” tab in the “Study-Estimation-Ace Inhibitors” channel on Microsoft Teams (link below).

  • Filename: Literature Review - ACE_ARB and COVID-19 incidence and complications.xlsx

The literature review text write-up has been incorporated into the Main Document file which is also available in the “Files” tab in the “Study-Estimation-Ace Inhibitors” channel on Microsoft Teams (link below).

  • Filename: MAIN DOCUMENT – ACEi Estimation

Mitch

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#20

Can it still be useful to add in this workpackage literature on the possible role of statins either alone or in combination with ARBs ? Has article below already been added to the list ? Thank you.

mBio. 2020 Mar 20;11(2). pii: e00398-20. doi: 10.1128/mBio.00398-20.

Hiding in Plain Sight: an Approach to Treating Patients with Severe COVID-19 Infection.

Abstract

Patients with COVID-19 infection are at risk of acute respiratory disease syndrome (ARDS) and death. The tissue receptor for COVID-19 is ACE2, and higher levels of ACE2 can protect against ARDS. Angiotensin receptor blockers and statins upregulate ACE2. Clinical trials are needed to determine whether this drug combination might be used to treat patients with severe COVID-19 infection.

#21

Thanks @Geert_Byttebier1. This is very helpful. We will incorporate this into the literature review / background. Also, I’ve shared your reference in the Microsoft Teams thread so that people who are working on the estimation study protocols can view.

#22

Very good. Thank you. Another relatively recent article (see reference below) also indicated potential impact of statin use. Statins were apparently also administered as acute medication during Ebola outbreaks in Africa las year, also documented in publications.

2020 Feb;48(1):51-56. doi: 10.1007/s15010-019-01335-0. Epub 2019 Jun 15.

Influenza virus infection: an approach to identify predictors for in-hospital and 90-day mortality from patients in Vienna during the season 2017/18.

Pawelka et al.

CONCLUSIONS:

Older age, history of atrial fibrillation and pneumonia are associated with increased risk of influenza-associated in-hospital and 90-day mortality. Statin use may decrease 90-day mortality.

#23

One of the supporting extra references as reported above :

J Public Health Policy. 2018 Aug;39(3):268-282. doi: 10.1057/s41271-018-0138-8.

What treating Ebola means for pandemic influenza.

Fedson DS

, 57, chemin du Lavoir, 01630, Sergy Haut, France. davidsfedson@gmail.com.

Abstract

Almost all new treatments being developed for the next influenza pandemic target the virus. During the Ebola crisis in West Africa, patients were treated with an inexpensive generic statin/angiotensin receptor blocker combination that appeared to greatly improve survival. These drugs target the host response, not the virus, and probably reverse endothelial dysfunction. Scientists and health officials have shown little interest in this idea. Yet, during the early months of the next pandemic, vaccines will be unavailable and treatment options will be limited. Physicians should be prepared to undertake clinical trials of widely available generic drugs to determine whether they improve survival in patients with seasonal influenza, other emerging virus diseases, and other forms of acute critical illness. Public health officials should give these studies their strong support. If successful, they will suggest a ‘bottom up’ approach to patient care that could be implemented worldwide on the first pandemic day.

Angiotensin receptor blockers; Ebola; Emerging virus diseases; Endothelial dysfunction; Host response; Pandemic influenza; Statins

#24

Hi,

This is Charu Gandotra. I recently joined OHDSI, introduced to it by Ana Szarfman. I am a cardiologist and work as a clinical reviewer at FDA. I will like to contribute to ACE-COVID 19 work stream. I am still trying to iron out some technical issues in joining Microsoft team meetings. Please let me know how i can contribute?

Thanks,
Charu.

#25

This paper talks about genetic variability in expression of ACE -2 and risk of corona virus infection. May be helpful to look at regional variations in outcomes of patients using ACEI or ARBs, and also compare ACEI with ARB.

https://www.nature.com/articles/s41421-020-0147-1.pdf

#26

Good morning! I am Qin Ryan, a new member of OHDSI, introduced by Dr. Ana Szarfman. I am a hematologist/oncologist who works at FDA reviewing efficacy and safety on new therapies. I am also a cell and molecular biologist. It is my honor to contribute to ACE-COVID 19 work stream. Presently, I am still try to navigate through OHDSI but would love to contribute. Thanks,

Qin

#27

Hot off the press: NEJM: Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19. A interesting article!
https://www.nejm.org/doi/full/10.1056/NEJMsr2005760?query=RP

#28

Hi Patrick, I am interested in this study-a-thon. How could I be involved in this event and make my contribution?

#29

@conovermitch, I’m happy to help out in any way I can on the literature review. Please let me know if there are any tools that you’re using to get started. I can be reached at jkohler@usaid.gov or juliannamkohler@gmail.com (some of the tools didn’t work on my government furnished equipment).

Many thanks,
Julianna

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