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Research questions that the OHDSI community can potentially answer to suport the COVID-19 response


(Melanie Philofsky) #21

Thank you for posting, @jenny_lane!

I’m interested in this statistic, “The CFR is higher among males compared to females (4.7% vs. 2.8%)” from the above. The non-data supported theory around the higher fatality rate in men is higher incidence of tobacco smoking rates in males versus females. Is a similar characterization seen in other countries? (something we can ask now) Does the evidence support this theory? (something we should ask in the near future)

The proposed standardization o the representation of tobacco use by @aostropolets and @Christian_Reich is very timely.


(belay birlie) #22

Hi all,

Great initiative!
I think (hope) the daily count of clinical COVD19 cases by the date of onset of symptom is readily available from most of the countries. Hence, I was thinking of conducting a real time prediction of the final size of the outbreak for multiple countries.


(Ed) #23

Hi all,

This article describes the potential role of ECMO (Extracorporeal Membrane Oxygenation) in the management of COVID19. Meanwhile, a review of ECMO from last year summarised that “Clinical trials of extracorporeal life support for acute respiratory failure in adults in the 1970s and 1990s failed to demonstrate benefit, reducing use of the intervention for decades and relegating it to a small number of centers. Nonetheless, technological improvements in extracorporeal support made it safer to use. Interest in extracorporeal life support increased with the confluence of 2 events in 2009: (1) the publication of a randomized clinical trial of extracorporeal life support for acute respiratory failure and (2) the use of extracorporeal life support in patients with severe acute respiratory distress syndrome during the influenza A(H1N1) pandemic.”

It seems that additional evidence on both the safety and effectiveness of ECMO is needed. Therefore, I would like to propose a device population-level estimation study with the CESAR trial as the ´target trial´. I think this will be a particularly difficult trial to emulate (control arm is conventional management and study inclusion was based on a Murray score >3·0 or pH <7·20 to name just two), but may well be worth the effort.

Any thoughts on the merit or otherwise of this potential study would be welcome!

Edit: Also to note, the WHO list of knowledge gaps for clinical management of severe and critically ill patients includes better understanding the “value of ECMO in the management of critically ill patients”


(David Vizcaya) #24

I see your point @Christian_Reich and it might be not so urgent to address this topic. I would like to see what data eventually shows though. There are aspects from covid19 progression that makes it interesting to investigate risk factors which might be different from previous corona outbreaks. See @MPhilofsky recent post in this thread around gender and smoking habit.


#25

Patrick, thank you for starting this discussion!

As I am taking care of patients who are on immunosupprants, my question is: for patients who are immunosuppressed (on biologics or chemo, etc), if the patient is infected with CoVID19, what is the risk of developing severe/critical CoVID/mortality?
I think it would provide critical information for clinicians to discuss risk and benefit when making decision to continue/initiate certain therapies. As we are still months away from having a vaccine to CoVID-19, it’d help clinically vulnerable patients.

Two possible approaches can be taken:

  1. Ideally we would need real-time data from current coronavirus outbreaks

  2. alternatively, can we learn something from old data on other viral respiratory infection?

Look forward to collaborate!


(Evan Minty) #26

One thing that is interesting about the COVID-19 is that similar to SARS, there is higher mortality in patients with cardiovascular disease. There also seem to be significant cardiac injuries (e.g. myocarditis) that are occurring with severe infection.

It’s known that SARS-COV-2 uses ACE2 (in part) for entry to into target cells. It’s also known that systemic ACE / ARB use increases the expression of ACE2 in cardiac cells. I can’t find reference to it’s effect in alveolar tissue, but ACE2 is expressed there, and thought to be involved in the pathogenesis of ARDS (effectively the presentation of severe COVID-19).

Could those on ACE / ARB be at risk for a more severe course due to up regulation of ACE2 at the cell surface, independent of other cardiac risk factors?

If so, perhaps widespread substitution of these agents for another might reduce the risk.

(I can’t find a reference to see how long it takes to return to previous expression levels after drug withdrawal)

The most natural group to look at here would be patients with isolated hypertension, many of which may be on an ACE, but also other agents with reasonable equipoise. Other patient groups on ACE I are also of interest.

https://www.bmj.com/content/368/bmj.m810/rr-2

COVID-19 and the cardiovascular system Nature Reviews Cardiology

Hoffmann M, Kleine-Weber H, Krüger N, Müller M, Drosten C, Pöhlmann S. The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells. bioRxiv 2020:2020.01.31.929042.


(Daniel Prieto-Alhambra) #27

thanks Evan, this is indeed an interesting question. one could look at the association between ace/arb2 use and severity/complications of covid when data is available. is this ace2-dependent mechanism specific of covid19 or is it shared with other previous infections? if so, maybe we could learn from previous outbreaks rather than waiting to have covid19 data.

the flu is also a myocardiotropic virus, by the way…


(Evan Minty) #28

As noted above, it’s also thought to be the entry target for SARS-Cov-1. The MERS spike appears to hit DPP4.

The narrative around ACE / ARB can be cast either way - I’ve also seen speculation ARB could be protective:
https://onlinelibrary.wiley.com/doi/pdf/10.1002/ddr.21656

ACE2 expression does seem to be necessary to infect cells in vitro.

Just does seem odd that in this disease a possible question is - is hypertension as bad or worse to have as immunosuppression?

Some basic queries, even before severity and mortality data, that could be asked to start to get a sense of any directionality:

% of people with isolated HTN on ACE/ARB in general population vs. those w/ isolated HTN and admitted to hosp. with COVID-19 vs. seasonal influenza
% of ppl with diabetes on ACE / ARB in general population vs. those admitted to hosp with covid-19 vs.seasonal influenza

Would also be worth looking at the cardiotropism relative to influenza as per your comment.

Also important to keep in mind in a network study that we are possibly dealing with different clades which may differ in their virulence / pathogenesis.

https://nextstrain.org/ncov?l=radial


(Cynthia Sung) #29

Referencing these articles: https://www.bmj.com/content/368/bmj.m810/rr-2 and https://pubmed.ncbi.nlm.nih.gov/32129518-angiotensin-receptor-blockers-as-tentative-sars-cov-2-therapeutics/ Questions that would be interesting to ask of the OHDSI network

  1. Is ACE inhibitor usage a risk factor for severe disease/death?
  2. Is AT1 blocker (e.g. losartan) a risk or protective factor for severe disease/death?

[OHDSI COVID-19] Review on the effect of ACE inhibitors and Angiotensin Receptor Blockers on COVID-19 incidence and complication rate
(Seng Chan You) #30

@Evan_Minty and @CSung I’ve also been interested in association between RAS blockers and covid-19. I added this to the github issue


(Rae Woong Park) #31

It seems that three university hospitals in endemic area in Korea can provide EMR data of patients infected with Covid-19. We will convert them into CDM with the support of Evidnet, and let researchers in OHDSI community use them in this Study-a-thon, if possible. Research themes can be expanded to fit rich data in the CDM from EMR. I will update whether the data will be available in time.


(Hainiwen) #32

Dear Dr Seng Chan You,

Available patient level open data collected by volunteers in mainland China include these links (as far as I’m aware):

and

https://shimo.im/sheets/6QQ3j8DKDqtCwyDV/QQKUx

(in Chinese)

Patient-level info included gender\age\geographic location\confirmed date\ contact with other patient ID\route\symptoms when diagnosed(partial)

Patient outcomes (in-hospital/released/deceased) are not available (as China CDC official wasn’t releasing clinical outcomes patient by patient).

So I guess sadly these data won’t be able to generate mortality rate…


(Daniel Prieto-Alhambra) #33

dear Rae
this would be great. please let’s email separately to discuss the logistics for remote collaborative analyses
bw


(Christophe Lambert) #34

That’s wonderful news, Rae! Just to confirm, will you have lab test results, including positive/negative tests for covid-19?


(Rae Woong Park) #36

Yes I will! Basically it will an indirect way. We will convert the hospitals’ data into CDM. The Achilles of the CDM will be publicly available. However researchers may not allowed to use ATLAS on the CDM. Instead, if researchers make their own analytic codes using ATLAS, then we can run in on the CDM and reply the results.


(Rae Woong Park) #37

The 3 hospitals agreed to provide their data.
Absolutely they have the RT-PCR result for Covid-19 confirmation. So I expect we can provide the data.


(Daniel Prieto-Alhambra) #38

Excellent. That should work just fine!


(Julianna Kohler) #39

Hi all,

I haven’t had time to read the full thread but wanted to add the work that the Global Digital Health Network is doing in a similar vein. They have a workshop planned for this Thursday to work out what questions should be answered and how members can answer the questions, and it seems like a good opportunity to join forces with them. I have pasted the email I received below which has a google doc outlining the questions that folks have thought of already as well as information about Thursday’s workshop.

As part of Thursday’s COVID Response Workshop from 8:30-Noon Eastern time, we will have Challenges Breakout Sessions where working groups will dive into current Surveillance, Prevention, Diagnosis, and Treatment issues for coronavirus response. 

We will look at each area to develop uses cases faced by four different cadres of people: Client, Provider, Manager, and Policy Maker. These use cases will help governments, donors, and health workers understand which digital health application would be the best solution for their context.

Please help us think through the questions each working group should be asking, on this Google Doc:
https://docs.google.com/document/d/1o1c-iYcruALvFQ26Q-aBW2aBb_2rw4ejxDX4xuZW-I0/edit?usp=sharing

Thanks in advance,
Wayan

PS: You RSVP’ed to this event already, right? Over 400 people will be joining us - don’t miss out!
https://www.eventbrite.com/e/how-the-global-digital-health-community-can-support-covid-response-tickets-98668354705

(Vojtech Huser) #40

From a totally opposite bucket:

I suggest we study chronic medication stockpiling (preparing for pandemic) by patients. Not sure how our normal methods account for stockpiling but we have a unique chance to study it in the month of March 2020. (early refills). Will the observed stockpiling predictably delay refills in several weeks after initial stockpiling.


(Nicholas Tatonetti) #41

Hey @SCYou,

Thanks for sharing your questions. The Korean data has already been so informative. I have a virologist colleague who has a specific hypothesis about possible protective co-morbidities with COVID-19. Do you know if co-morbidity data is going to be made available from the Korean data set?

Thanks!


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