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Draft proposed updates to risk factors/social determinants of health section #881

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@rando2 rando2 commented Feb 24, 2021

Description of the proposed additions or changes

This is a work in progress that I'm posting so it's not secretly on my computer!
The goal is to tie the social side and the clinical side together via allostatic load/inflammation

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  • Pre-prints cited in this pull request have a GitHub issue opened so that they can be reviewed.

@rando2 rando2 marked this pull request as draft February 24, 2021 20:00
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Hey @rando2, I just gave a brief review. I can help more with inflammation/comorbidity sections after the vaccines paper

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HM Rando and others added 2 commits March 9, 2021 10:48
Co-authored-by: Ronan Lordan <[email protected]>
Co-authored-by: Anthony Gitter <[email protected]>
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However, genetic variants associated with outcomes within ancestral groups are far less surprising than genetic variants explaining outcomes between groups.
Alleles in _ACE2_ and _TMPRSS2_ have been identified that vary in frequency among ancestral groups [@doi:10.1186/s12916-020-01673-z], but whether these variants are associated with COVID-19 susceptibility has not been explored.
However, genetic variants associated with outcomes within ancestral groups are far more common than genetic variants explaining outcomes between groups.
Alleles in _ACE2_ and transmembrane protease serine protease-2, which is involved in proteolytic priming of SARS-CoV-2 for cell entry [@individual-pathogenesis], have been identified to vary in frequency among ancestral groups [@doi:10.1186/s12916-020-01673-z], but whether these variants are associated with COVID-19 susceptibility has not been explored.

Instead, examining patterns of COVID-19 susceptibility on a global scale that suggest that social factors are of primary importance in predicting mortality.
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Suggested change
Instead, examining patterns of COVID-19 susceptibility on a global scale that suggest that social factors are of primary importance in predicting mortality.
Instead, examining patterns of COVID-19 susceptibility on a global scale suggests that social factors are of primary importance in predicting mortality.

Similarly, preliminary findings indicate that nutritional status (e.g., vitamin D deficiency [@doi:10.1210/clinem/dgaa733]) may be associated with COVID-19 outcomes, and reduced access to grocery stores and fresh food often co-occurs with environmental racism [@url:https://journalhosting.ucalgary.ca/index.php/jisd/article/view/70753/54416; @doi:10.1056/NEJMp2021264].
Taken together, the evidence suggests that low-income workers who face greater exposure to SARS-CoV-2 due to their home or work conditions are also more likely to face environmental and social stressors associated with increased inflammation, and therefore with increased risk from COVID-19.
In particular, structural racism can play an important role on disease severity after SARS-CoV-2 exposure, due to consequences of racism which include an increased likelihood of poverty and its associated food and housing instability.
Similarly, preliminary findings indicate that nutritional status (e.g., vitamin D deficiency and other nutritional deficiencies [@individual-nutraceuticals]) may be associated with COVID-19 outcomes, and reduced access to grocery stores and fresh food often co-occurs with environmental racism [@url:https://journalhosting.ucalgary.ca/index.php/jisd/article/view/70753/54416; @doi:10.1056/NEJMp2021264].
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perhaps this sentence would fit better in the section above that discusses the link between poverty and inflammation (so right before line 211, before the discussion of environmental racism)


During the pandemic, a number of risk factors have been associated with COVID-19
These include health conditions such as obesity, diabetes mellitus, and heart disease [@url:https://www.mayoclinic.org/diseases-conditions/coronavirus/symptoms-causes/syc-20479963; @doi:10.1016/j.jinf.2020.04.021].
An observed association among racial and ethnic background and COVID-19 outcomes has also led to racial and ethnic minorities frequently being included on the list of groups with increased susceptibility (e.g., [@url:https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/index.html]).
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Something I'm wondering here- this paper discusses COVID-19 on a global scale, but I feel like this sentence is very country specific (because as you outline below, racial and ethnic background on a global scale does not seem to be associated with COVID-19 outcomes, but minority racial status seems to be) Just thinking that you might want to specify that this observation is context-dependent? such as "An observed association in several countries among racial and ethnic background and COVID-19 outcomes has also led to racial and ethnic minorities frequently being included on the list of groups with increased susceptibility"

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This is a really good point! I will clean this up.

During the pandemic, a number of risk factors have been associated with COVID-19
These include health conditions such as obesity, diabetes mellitus, and heart disease [@url:https://www.mayoclinic.org/diseases-conditions/coronavirus/symptoms-causes/syc-20479963; @doi:10.1016/j.jinf.2020.04.021].
An observed association among racial and ethnic background and COVID-19 outcomes has also led to racial and ethnic minorities frequently being included on the list of groups with increased susceptibility (e.g., [@url:https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/index.html]).
However, it is well documented that these health conditions occur at higher rates in communities of color.<!-- To Do: Add citation-->
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and same question here- isn't this statement more specific to communities of color within majority-white countries?

Higher Sequential Organ Failure Assessment (SOFA) scores have been associated with a higher probability of mortality [@doi:10/ggnxb3], and comorbid conditions such as cardiovascular and lung disease as well as obesity were also associated with an increased risk of hospitalization and death, even when correcting for age and sex [@doi:10.1136/bmj.m1985].
Diabetes may increase the risk of lengthy hospitalization [@doi:10.1016/j.cmet.2020.04.021] or of death [@doi:10.1016/j.cmet.2020.04.021;@doi:10.1007/s00592-020-01546-0].
[@doi:10.1111/dom.14057] and [@doi:10.1152/ajpendo.00124.2020] discuss possible ways in which COVID-19 and diabetes may interact.
Higher sequential organ failure assessment (SOFA) scores have been associated with a higher probability of mortality [@doi:10/ggnxb3], and comorbid conditions such as cardiovascular and lung diseases as well as obesity were also associated with an increased risk of hospitalization and death, even when correcting for age and sex [@doi:10.1136/bmj.m1985].
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One thought I've been having while reading through this is the use of the word "obesity." I've been trying to read more about the supposed connection between obesity and COVID-19 infection/outcomes (like this review- @doi.org/10.1111/obr.13128) but I don't see mention (except for one included paper) of controlling for other health conditions a person might have (type II diabetes, hypertension, cardiovascular disease) or their race, socioeconomic status, and access to healthcare or discrimination experienced while seeking healthcare. For we know the characterization of obesity as a disease is steeped in racism, and that people of higher weights experience excessive discrimination when seeking healthcare (for example- an H1N1 study found a correlation between higher weight and complications/ risk of death, but also that higher weight people were less likely to be prescribed early antiviral treatment...thus indicating healthcare discrimination could be a confounding variable @doi.org/10.1080/23744235.2016.1201721). I feel like obesity is often used as a proxy when researchers/clinicians are really talking about metabolic disturbances or other health conditions... just wondering if you all want to rethink the use of the word/ this framing in the paper. I'm happy to do more research on the topic or help rephrase things if you would like! I found these articles really helpful for learning more: url:https://sph.umich.edu/pursuit/2018posts/3-ways-public-health-professionals-can-combat-weight-stigma.html; url: https://www.huffpost.com/entry/fat-covid-19-pandemic-obesity_l_5f736f60c5b6e99dc3336e3e

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This is just my opinion, but I think that in the context of a review it would be better to continue to say "obesity." We could of course add that the problem is probably metabolic conditions associated with the high weight, rather then the weight itself, but I don't think we should change what the original research papers reported.

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I would be okay with saying "high BMI" if you feel very strongly that the word "obesity" itself is pejorative, but I don't see how that would actually help.

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To maybe give some context to your observations @juliettemarie0405

It is proposed that the underlying link between obesity and increased risk of COVID-19 is low-grade or systemic inflammation. Hence why other conditions such as diabetes, hypertension, CVD, and aging are also associated with increased risk of COVID-19 (all characterized by systemic inflammation-https://www.nature.com/articles/s41366-020-0597-4; and https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html). Many papers don't control for one or the other because many people have more than 1 of these conditions. You can be both type II diabetic and obese and even have hyperlipidemia, which in turn would increase one's risk of COVID-19. Heaped together, many people that are overweight or obese have metabolic syndrome, which is a clustering of these conditions. These non-communicable diseases (NCDs) or comorbidites are more prevalent in African Americans and you can be sure that social determinants of health is one of the reasons for that.

There was a similar increased risk associated with NCDs for H1N1, but in contrast to COVID-19, obesity and asthma were not associated with increased risk [https://doi.org/10.1371/journal.pmed.1001053].

You are right that obesity of course has connotations attached, but I think from a scientific standpoint it is fair to use the term. Particularly since it is a key component of metabolic syndrome. However, I take your point about from the example of the H1N1, there is certainly medical prejudice. Maybe we can acknowledge this somehow in the text.

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I think that some of the controversies that become associated with the idea of "risk factors" are related to the fact that different people and fields use the term in different ways. Some use the term only when they believe there is a direct cause-and-effect relationship, while others use the
term for anything that is a significant statistical predictor of an outcome (even if it might be a proxy for something else that's harder to measure). It's unfortunate that the same word is used in those two different ways, but we cannot fix it here. The former definition is more natural for what we ordinarily mean by risk, in the sense of somebody doing something dangerous. But I think the latter definition is actually more common in the field.

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I think it would be great to link this back to the medical discrimination that @tlukan wrote about in text below -- and also, I know @RLordan and I are really hoping we can make it clear how inflammation (which we'll need to make sure is contextualized alongside experiences/environment because they are so closely tied together) ties a lot of fragments of the COVID-19 story together.

In this case, obesity/high BMI/whatever we want to call it can be view as a signal of inflammation, but it is also associated (causally or not) with other factors that can influence health outcomes (medical discrimination, as @juliettemarie0405 mentioned, or also racial discrimination since BMI is not an inclusive measure, also often prevalent in places with limited access to health-related resources and/or low SES, etc.)

One thing I was hoping to do while I was writing this draft was to try to drag any "I'm a biologist, I don't care about social sciences" people reading it along with us by working out in circles from things they would view as biological (e.g., obesity) and eventually tying it in to systemic effects that elevate inflammation. It seems like I need to revisit this because it's not working the way it is! I really appreciate all the feedback (and the references @juliettemarie0405!)

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All true, I think it would be fair to say in my world we often dip into both definitions blindly haha @dziakj1

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Also, welcome @juliettemarie0405 !

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Thank you @RLordan! And thank you for that very helpful explanation of the role of inflammation in all of this, and for pointing out the difficulties in controlling for comorbidities. I really appreciate the opportunity to discuss this with all of you, and I am excited by the idea of introducing this discussion to readers as well. @rando2 I really like how you framed it- that the underlying thread in all of this is inflammation, that there are many causative forces, and that higher weight should be reconceptualized as a "signal of inflammation" rather than a condition in and of itself. Even if you all decide to move forward with the term obesity, I really like @RLordan's suggestion of acknowledging how medical prejudice (and racism, poverty, fatphobia) inherently complicate how we understand associations identified in the literature.

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rando2 commented Mar 24, 2021

@juliettemarie0405 can you check your author information that I added? Just leave notes for anything you want filled in or that is wrong and I can fix it -- also, just note that you are in agreement with the code of conduct and whether you have any conflicts of interest! (I know you also sent me an email about this, I'm sorry I've been so behind!)

(Author order is determined at the end, so I put 0 for a placeholder, lol)

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@juliettemarie0405 can you check your author information that I added? Just leave notes for anything you want filled in or that is wrong and I can fix it -- also, just note that you are in agreement with the code of conduct and whether you have any conflicts of interest! (I know you also sent me an email about this, I'm sorry I've been so behind!)

(Author order is determined at the end, so I put 0 for a placeholder, lol)

just did!

Co-authored-by: juliettemarie0405 <[email protected]>
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dziakj1 commented Mar 29, 2021

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dziakj1 commented Mar 29, 2021

Also, it looks like at least some people have done some research into why higher-BMI patients do worse with COVID-19. The relationship holds up even in an all-white subsample, so it isn't just confounding by racial background.
https://www.frontiersin.org/articles/10.3389/fgene.2020.586308/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521361/

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dziakj1 commented Mar 29, 2021

@rando2 I found this preprint talking about allostatic load as a mediator, although it appears to be more of a narrative review rather than a new study:
https://www.medrxiv.org/content/10.1101/2021.01.24.21250397v1.full.pdf

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dziakj1 commented Apr 3, 2021

This paper just came out. It is a rather fancy causal mediation analysis of British data, arguing that a sizable reason for racial differences in COVID rates in the UK is "material disparities" (economic poverty). It uses some rather difficult statistical methods that I've only started to learn about myself, so if you are interested, I'd try to write a paragraph on it. However, it depends on what you want to do with this paper and I don't know whether it would fit in or not.
https://academic.oup.com/eurpub/advance-article/doi/10.1093/eurpub/ckab041/6179315

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dziakj1 commented Apr 3, 2021

Also, this preprint looks at seropositivity rates in different demographic groups in the US last year, which might help to provide a look at overall infection rates including mild cases. For example, the rates were higher in younger than older participants, and in female than male participants; even though if you counted deaths the risks would be higher for older than younger and for male than female. The Black/African American demographic was very disproportionately affected.
https://pubmed.ncbi.nlm.nih.gov/33532807/
The data is a bit old though.

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dziakj1 commented Apr 8, 2021

Hello @rando2 and @RLordan !
I don't know how to work this in, but I think it's very related to inflammation.
This very new JAMA Pediatrics paper with a large sample provided evidence that MIS-C in children was due to a "delayed" immune reaction to covid-19. They also mentioned in passing that most children with this syndrome were Black or Hispanic -- although that doesn't necessarily mean that they are more vulnerable to MIS-C per se, it just might be that they are more likely to get COVID or more severe COVID, and the MIS-C may follow later. I know very little about inflammation but my rough understanding is that it has to do with the immune system. I feel like this paper is really important but am somewhat deficient in the skills I would need to explain it. If you like, I could put one of my short and vaguely worded sentences, that are just wrappers for citations, in there somewhere. But somebody who knows about immunology could do better.
Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic
Ermias D. Belay, MD; Joseph Abrams, PhD; Matthew E. Oster, MD; et al.
https://jamanetwork.com/journals/jamapediatrics/fullarticle/2778429
The paper is discussed in an editorial here:
https://jamanetwork.com/journals/jamapediatrics/fullarticle/2778430

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dziakj1 commented Apr 24, 2021

Hello again! Another large report about inequities has come out, this one in the Annals of Internal Medicine on April 20:
COVID-19 Inequities Across Multiple Racial and Ethnic Groups: Results From an Integrated Health Care Organization
https://www.acpjournals.org/doi/10.7326/M20-8283

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dziakj1 commented May 4, 2021

This is ANOTHER new large study from the UK:
Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00634-6/fulltext

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