Circulation on the Run: Discussing Circulation’s Response to COVID-19

This week's episode is special: To start 2021, Circulation's
Digital Strategies Editor, Amit Khera, hosts a look back at
Circulation's response to the Covid-19 pandemic. Circulation's
Executive Editor James de Lemos and Senior Associate Editor
Biykem Bozkurt discuss the initial days of Covid manuscript
submissions to Circulation. Then Amit interviews author Fatima
Rodriguez and her findings of racial and ethnic differences of
patients suffering from Covid-19. Finally, Amit interviews
authors Nicholas (Nick) Hendren and Justin Grodin as they discuss
their article, which was one of the first science outputs from
this AHA COVID registry.


TRANSCRIPT BELOW:


Dr. Amit Khera:


Well, welcome to Circulation on the Run. This is Amit Khera. I am
digital strategies editor for Circulation, and I have the
privilege of standing in for Carolyn Lam and Greg Hundley on this
very special edition this week. We have no Circulation issue, so
we get to use this and we thought we would use it for a really
special look at COVID the Circulation response. It's a time to
take a pause and reflect on what we've seen so far this year and
what science and initiatives have come out of Circulation. And
it's a real privilege today to be joined by first senior
associate editor of Circulation, Biykem Bozkurt, who's professor
of medicine at Baylor College of Medicine, and also James de
Lemos. He's executive editor of Circulation and professor of
medicine at UT Southwestern Medical Center. Welcome to you both.


Dr. James de Lemos:


Thank you.


Dr. Biykem Bozkurt:


Thank you, Amit.


Dr. Amit Khera:


Well, Biykem, I'm going to start with you. I remember when COVID
came out, it was, we were all overwhelmed. The data were coming
fast and furious. Most importantly as cardiovascular specialists
we wanted to know how to manage these patients and what
manifestations we're seeing. Things were coming from all over the
world, and you were tasked with the challenge of, well, how do we
organize and curate all this? And what can Circulation do to be
most helpful in this response? And you came up with some really
creative ideas that I really lodge you for. Maybe you can tell us
a little bit about what was going through your mind when this was
starting and what are some of the initiatives you started around
that?


Dr. Biykem Bozkurt:


Thank you, Amit. And I really appreciate your pushing it to
reflect. In early March it was clear that COVID was surging and
we had to create a platform rapidly to disseminate the insights
and the best practices from around the world in a timely fashion,
and also inform future research for the fight against COVID. We
discussed amongst the senior editors, and it was apparent early
on that we would not have large-scale multicenter trials. And
most of the information was going to come from site experiences
and our cohorts, which were so valuable, and everybody was
yearning for that information. With that framework in mind, we
thought the best platform would be to do a call for submission of
rapid research letters. And also we thought of interviews with
experts from the hotspots, and we rapidly assembled a Circulation
COVID editorial team, which comprised of me along with my
colleagues, Salim Virani, Erin Michos, and then both of whom are
the guest editors at Circulation, along with Mark Drazner, Darren
McGuire and yourself.


Dr. Biykem Bozkurt:


And we created a call for rapid research letters for COVID and
also started doing short video interviews from pandemic hotspots
around the globe. We wanted these interviews to be dynamic,
informative, conversational, both recognizing the crisis and the
human factor as well as the best practices. We were so hungry for
information. So we thought of a dyad approach where the
interviews would be conducted by early career fellows in
training, along with regional experts from the hotspots who were
leading the fight formulating solutions. And we are so indebted
to these experts and heroes for sharing their stories and
experience on the cardiovascular presentations and the practices
and how they were managing their patients. And these were called
COVID updates from the front lines.


Dr. Biykem Bozkurt:


We had approximately 19 interviews with leaders from Seattle.
That was one of the early hotspots. Then we moved on to Singapore
because they were having such valuable and successful
interventions. Then we went over to Madrid, Spain, where there
was a huge hotspot, of course New York City. Then we interviewed
with Milan, Italy, Brescia, Italy, Wuhan, China, New Orleans,
South Korea, Salt Lake City, Paris, French, Houston, Texas,
Atlanta, San Francisco, Delhi, India.


Dr. Biykem Bozkurt:


And we also try to address not only the local expert's approach
to how to treat and manage and what they were seeing, but also
strategically how the health disparities were being handled, how
the emergency room or ICU clinicians were tackling COVID. We also
try to provide a nursing perspective and even pandemic modeling.
For our call for research letters we had approximately, or more
than 1,000 papers submitted, 414 of those were original research
letters and about 265 as research letters. So I think it was
truly a gratifying experience that we were able to provide a
voice for the frontline cardiovascular specialists, providing
what they were seeing, what they were doing, and also a perhaps a
platform that was quick enough, dynamic enough for us to
disseminate information. And also a platform for publications as
research letters, which are concise and addressing the issue at
hand and creating a portfolio by which all the investigators
could voice their observations.


Dr. Amit Khera:


Well, listen, first and foremost, that was a heroic effort and a
huge volume of different components, both research components,
regional research articles, research letters, and then the
videos. And I'll say those videos included fellows. I know I
watched many of them before I went on service and taking care of
patients to learn what people were doing. And that's so different
than what we do in a scientific journal where we peer review and
all that. And I can't tell you how helpful that was. And then
something else you said was the personal experience. I remember
watching a few physicians talking about what it meant personally
for them and their families and quarantining and how hard that
was and the human toll. And boy, that was really amazing. And I
know we'll look back on those years to come and as we think about
what COVID was when it first started.


Dr. Amit Khera:


I'll pivot a little to some of the science. I think having seen
this from a different vantage point, at first you weren't sure
how many papers you'd get. We were all looking for sort of
kernels. And then all of a sudden there's a deluge of papers,
right? Can you talk to that experience about how you learned how
to curate all this when it was sort of started slow and then it
was overwhelming?


Dr. Biykem Bozkurt:


We knew we would get a lot of papers. We didn't realize the true
magnitude. At the beginning we thought that the assigned group,
which we call the COVID editor group would be able to handle
this. And thus we were trying to triage and provide a structured
approach to this. It was quickly clear with James and Joe's and
Darren's help that we needed the remainder of the whole editorial
board. I remember initially we started with that small group and
immediately expanded it to the larger group for us to be able to
tackle.


Dr. Biykem Bozkurt:


I think starting with March, there was a steady rise in the types
of papers. The interesting concept was the observations
eventually start coming with a certain repeated theme. And of
course the ones who provided the initial observations usually had
the innovative part of the initial, the first one to recognize
it. And there was a lot of debate. For example, when we were
first seeing the papers about, or the research letters about the
clots we were saying, or asking the questions, "Whether these
were higher than the other ICU patients and so forth?"


Dr. Biykem Bozkurt:


But as the numbers increased, it was the summation of the gestalt
of I think what the papers were providing was also moving the
field. So not only the volume, I think that was a very
interesting experience. Of course how to deal with that on an
operational level, at a journal level. But also cataloguing and
creating these, okay, these appear to be myocarditis, these
appear to be potentially the clots. And then recognizing the how
the story's evolving about COVID. And of course, intermittently
we had the commission request and ask individuals to provide
reviews that are with the insights, creating the synthesis from
this culmination of this large volume of papers. And I think we
try to do that in a timely manner periodically.


Dr. Amit Khera:


Yeah.


Dr. James de Lemos:


Actually just how hard it was to evaluate science in the midst of
a pandemic. You know, what these investigators were doing in the
midst of their surges was frankly heroic in the beginning. They
were terrified, didn't know what was happening in their sites and
they were submitting research. But the challenge is that it's not
the kind of research we're used to evaluating in Circulation in
terms of very well controlled clinical studies with good control
groups and clear experiments. We were forced to evaluate research
in a war zone basically and decide when something was actionable
enough that we thought the clinical community could get ahold of
it.


Dr. James de Lemos:


And at the same time we also had to think about our mission to
publish durable science that will last beyond a few weeks or few
months of the pandemic. And it was a real challenge and credit to
Biykem and Augie here, who's running this podcast for the nights
and weekends that we're done evaluating these and the many
discussions about really what's the bar for research to get
published in the midst of a pandemic. None of us and any of the
journalists had ever been through this before.


Dr. Amit Khera:


I think those are great points. And I may even add to that just
as much as there was the wanting to get things out that would
help clinicians on the front lines, also responsibility of not
publishing something erroneous where people would do the wrong
thing. And we've certainly seen that along the way. So that was
an added challenge. James, I'll pivot to you a bit more on this,
in reflection, if you think about the papers now that you'd be
able to look back, what are some of the ones that you remember
the most, or you think were most impactful published in
Circulation so far?


Dr. James de Lemos:


Well, some of the ones at the very beginning that were really
written with almost a 24 or 36 hour cycle to get information out,
there was a research, a review paper rather by Nick Hendren and
Les Cooper that really came out almost the first weekend after
this group launched. Biykem was involved in that. It was a
remarkable effort to summarize really weeks old data on the
potential cardiovascular complications. And it was an instant
classic. Another one I think that has been tremendously important
and durable was the report from Bonnet's group in France on the
MIS-C syndrome in children that has been really paradigm
changing. I think it was, it won the Willerson award as our top
clinical paper of the year because the editors and editorial
board felt that this was the most impactful paper we published of
all papers in the year. And I think it certainly was amazing work
to pull together that kind of series in such a short period of
time and define a syndrome really that had never been reported
before.


Dr. Amit Khera:


Yeah. You know, I'm looking here out of the maybe near a 1,000
papers or so of different varieties that came through, those are
certainly two very memorable ones and several others. Biykem, I'm
thinking about some other articles and even some really
interesting frame of reference pieces that people, just sort of
personal reflections. What are some of the ones that you
remember?


Dr. Biykem Bozkurt:


The sequence of how it evolved is truly, left a sort of enduring
impact on me. The first one that I remember was Kevin Clarkson's
paper that provided the initial review, and we all were reading
that, of course. Nick Hendren and of course Mark Drazner's paper
also added a larger framework of the whole spectrum of
cardiovascular disease or cardiovascular abnormalities with
COVID. We, I think, try to provide a right balance in terms of
the research papers and have received a large scale of papers on
DVT and PE. And we then clustered quite a few of those. One of
which was from Wuhan, China and the others were from U.S. And
that became a very nice complimentary portfolio of three DVT PE
papers, which I thought was very helpful at that juncture,
because that came a little bit later in the timeframe. I can't
recall, I think it was around June timeframe where we were able
to formulate, really, this is truly a pattern.


Dr. Biykem Bozkurt:


The other very interesting paper that I remember is a series of
echocardiographic imaging of all hospitalized patients from
Israel. This was published in July. This was one of the first
structured screening by echocardiography of all comers to the
hospital. And it was about a 100 patients and it was by Topilsky.
If I remember correctly, it was published in July. And that was
the first one stating that a large number of patients had
abnormality in the cardiac structure and predominantly RV, which
until that time it was anecdotal case reports. We were all
hearing about the RV and PE.


Dr. Biykem Bozkurt:


Then I think in July we had Peter Lewis' very nice review. And of
course, Damien Bonnet's the multi-system inflammatory syndrome in
the pediatrics, especially how to manage it. We also had a HRS
partnership on guidance for how to do EP studies during the time
of COVID, and a variety of frame of references. Some of which
were about certain different approaches. We had one paper about
senior woman leaders as to how they were supporting their
colleagues. We also had early career faculty members who had
provided their frame of references about social consciousness and
ethical dilemmas, all of which were a true complimentary
portfolio, providing not only the scientific expertise about
human factor in managing this.


Dr. Amit Khera:


Well, you certainly have a great perspective on all the articles
that came through, Biykem, and listed several of the highlights
and James, I'm going to pivot you and ask you, what comes next?
As one of the senior editors along with Biykem for Circulation,
what do we need to see next in cardiovascular space or literature
as it relates to COVID? I appreciate there's also what's
happening with COVID in general, but what do we need to know and
what's the level and bar of science now?


Dr. James de Lemos:


The bar is back to requiring excellent science, even for COVID
cardiovascular disease, really. Because we know enough about the
disease that we need the best information that's clinically
actionable and meet sort of usual circulation standards. And what
I'd say we need next is we need long-term outcome data. So we
have a lot of information about short-term cardiovascular
complications of the illness, but the next wave, and we're going
to get through this, right? The end, the light is on for the end
of this thing. But then the next phase is what's the long-term
implications of cardiac injury that occurs in the hospital? What
are the cardiovascular manifestations of these long haulers? And
I think that will be the kind of research that's durable really
over the next few years.


Dr. James de Lemos:


I'm very, very hopeful that we won't be talking about
hospitalized COVID in 2022, that that will run its course and not
be a dominant theme in Circulation. But I do think we're going to
need long-term follow-up of cardiovascular issues for these
patients. Particularly given the subtle cardiac abnormalities
that Biykem was talking about that we've been reporting in the
hospital.


Dr. James de Lemos:


The other piece I would just say is that we know almost nothing
about cardiovascular manifestations of non-hospitalized COVID.
Almost everything that we've published and other journalists have
published has been about the minority of patients that get
hospitalized. But we do need to know more about the many larger
proportion that never get hospitalized.


Dr. Amit Khera:


That's a nice segue when we talk about sort of high quality
science and maybe slowing things down just a bit to make sure
we're getting the best answers. And that's a pivot to the AHA
COVID-19 Cardiovascular Disease Registry, something which you
have co-chaired and spearheaded. And we recently had a milestone
at DHA scientific sessions. We had the first output just in a few
months to already have some high-quality research coming out,
we're going to hear in just a bit from two of our featured
articles that were leg breaking science out of that registry in
shortly. Tell us a little bit about the inception of that
registry, what led to it and sort of how did it form?


Dr. James de Lemos:


Well, the impetus was really the same as what Biykem was talking
about with her nights and weekends trying to generate information
for practitioners. It was that feeling of powerlessness that we
all had early on, knowing that this surge was coming, developing
in other parts of the country and realizing that we knew nothing
and all of us felt the need to fight back. And as you know, Amit,
this really grew out of work of our young people that we
developed, or I should say we, meaning our fellows developed a
program to teach us about COVID and to study COVID in the
patients at our two teaching hospitals. And that really led us to
realize that the field needed generalizable knowledge that was
beyond single center experiences and their work really directly
led to the idea to approach the American Heart Association about
a multicenter registry and then Sandeep Das, one of our associate
editors and a faculty member at UT Southwestern and I pitched
this to the AHA and then we put together a great steering
committee and launched this.


Dr. James de Lemos:


And I think the unique thing about this that we tried to do was
in the same, we recognized that the window for discovery was
short and the usual way of registry research wouldn't work. And
so what we did is we democratized the process. So we allowed
multiple teams of investigators to be doing science
simultaneously on a secure platform at the AHA, the precision
medicine platform. And that's allowed dozens of projects to
forward in parallel so that within this six month timeframe we
have these two papers published, but we've got a lot of other,
what we hope will be important work that can still make a
difference in the pandemic.


Dr. Amit Khera:


Well, thank you for that. And I won't steal this under the
upcoming articles to talk more, but congratulations to you on
seeing this come to fruition, all the fruits of your labor in a
very short amount of time. So we look forward to seeing many,
many more papers coming out of it. I want to wrap up by just
saying, I know we are certainly not done with the COVID pandemic,
but it is a new year by the time this podcast comes out. And so
we want to make sure we have time to reflect on what lessons were
learned. What we learned about scientific publishing in these
really trying times. And I want to congratulate you both on
coming up with some very creative strategies to be as
contributory as possible to what the field needed at the time.
And I think you achieved that and we look forward to continuing
to learn from Circulation and from the work coming in about this
pandemic and many more things to come. So thank you both for your
time today.


Dr. James de Lemos:


Thank you.


Dr. Biykem Bozkurt:


Thank you.


Dr. Amit Khera:


So now we're moving on to the featured article. This is the first
of two, and I'm fortunate to be joined by my colleague here, Dr.
Fatima Rodriguez, who's an assistant professor at Stanford in the
division of cardiology. Welcome, Fatima.


Dr. Fatima Rodriguez:


Thank you so much, Amit for the invitation.


Dr. Amit Khera:


Well, you had this really important article on racial and ethnic
differences in presentations and outcomes in those hospitalized
with COVID and certainly there's been a lot about racial and
ethnic differences. Tell me a little bit about the genesis of
this particular article. What made you decide to use the registry
early on as one of the first studies to evaluate this registry?


Dr. Fatima Rodriguez:


So as you heard from Dr. James de Lemos and Sandeep Das, the
American Heart Association very rapidly created this registry to
democratize and accelerate the way we do research during the
pandemic. And this topic of racial ethnic disparities was right
off the bat selected as a priority area because of the inequities
that we're seeing, and that have been magnified by the COVID-19
pandemic.


Dr. Amit Khera:


Well, there's so much that you found and when it came to who was
affected and who ended up in hospital with COVID and then
obviously exploring some outcomes, maybe tell us a little bit
about what are some of the main findings of this work?


Dr. Fatima Rodriguez:


We had a lot of significant findings, but I would say that some
of the most important findings is that black and Hispanic
patients really accounted for over half of the hospitalizations
and the deaths in the registry during this first data cut. A
third of the patients that were hospitalized were Hispanic and a
quarter were black. Asian patients that we also studied had more
severe presentations when they were admitted to the hospital. We
were also surprised that race and ethnicity itself was not
independently associated with worse in-hospital outcomes or other
adverse cardiovascular outcomes. But again, this suggests that we
really need to move upstream from hospitalizations to deal with
the factors that result in the higher rates of hospitalizations
for these underserved communities.


Dr. Amit Khera:


You know, I think you just summarized it so well. And I think for
many of us that saw this paper, we saw that there was no
difference in in-hospital outcomes in general and after
adjustment, which I think that was a little surprising. Maybe we
shouldn't have been surprised. Or do you think that perhaps
looking at all the sort of media and the press about adverse
outcomes we should have thought differently, or do you think this
is the actual finding that one can expect?


Dr. Fatima Rodriguez:


Yes, we were surprised as well. And our hypothesis was that race
and ethnicity would be independently associated with worse
in-hospital death, but also mace. But it actually turns out there
have been many publications across many different sites in the
United States that have documented similar findings. Again, the
caveat being here is that these patients were hospitalized and as
a clinician you and I know that once people get in the hospital,
at least for a disease like COVID-19, the care is fairly
protocolized. And more of the variation mortality has to do with
where these individual patients are hospitalized. And again, not
surprising with the new disease that there's a lot of in-hospital
variation. So not to say that there aren't disparities, but at
least the hospital itself does not seem to be a cause of
disparities and outcomes by race and ethnicity.


Dr. Amit Khera:


I mean, that's an incredible important finding to your point
about once you get to the hospital people seem to do comparably
well. So I think you said this in your conclusion as well. We
really need to work upstream and is also profound that 58% were
Hispanic or non-Hispanic black that were hospitalized with COVID.
What are some of the upstream things we could be doing?


Dr. Fatima Rodriguez:


Yes, and this finding has been consistent across many studies.
And I think that this reflects the over representation of these
communities and the essential workforce, right? People that are
not able to isolate. People that need to show up to work every
day. People that live in multi-generational households and
therefore exposed to the virus and higher rates of transmissions.
So first I would say we need to try to do things to prevent the
transmission in the first place in the communities. For essential
workers they need to be provided the protective gear to again
prevent them from the transmission. And now things are different
then when we did this study. Now we have a vaccine that's about
to be rolled out that we were discussing before, and we really
should prioritize these communities in the vaccine rollout as
well.


Dr. Amit Khera:


All great points. And as we drill down a little deeper into some
of your findings, I think one that really stuck out to me was how
much younger the Hispanics and non-Hispanic blacks were. I think
average age of 57 and 60 versus 69 in non-Hispanic whites. Tell
me a little bit about your thoughts on what is driving that
younger age as well?


Dr. Fatima Rodriguez:


Yes, I agree that that was a fairly striking finding, especially
Hispanic patients were on average 57-years-old compared to
non-Hispanic whites who were 69-years-old when they were
hospitalized. So more than 10 year difference. Again, I think a
lot of this reflects the nature of the workforce and help
individuals are higher rates of getting exposed, but also likely
reflect some of the underlying co-morbidities. Remember, these
are patients that are sick enough to require hospitalization. And
again, we know that individuals that have higher rates of
diabetes, obesity, and other risk factors have a higher tendency
to be hospitalized.


Dr. Amit Khera:


You know, you also looked a bit at Asians, I should mention that.
I think some of the findings were increased respiratory
complications and perhaps some issues related to delayed some of
the observations around Asian patients.


Dr. Fatima Rodriguez:


So the Asian patients did comprise a smaller portion of our
registry, but again, still a notable finding that they tended to
be sicker at time of presentation. We developed a
cardio-respiratory disease severity scale specific to COVID,
modified from the WHO scale. And again, found that patients even
after adjusting for all other factors did tend to have a higher
disease severity when they came in. One of the hypothesis of why
this was the case is that they tended to have longer delays from
symptom onset to both hospital arrival and to the diagnosis of
COVID-19. And our study didn't look up why, but there have been
some other studies that have suggested perhaps that there's been
some hesitation in the Asian community to seek medical care for a
variety of factors.


Dr. Amit Khera:


You know, and I think as we try to think about what are some
implications of this work and what are next steps that could be
one is to how do we enhance understanding of the need for prompt
care in the Asian community, that could be one take home. One
other tantalizing finding was this observation of less Remdesivir
use amongst non-Hispanic blacks in this study, you made a point
of that. What do you make from that, and what are some of the
reasons you think are for that?


Dr. Fatima Rodriguez:


Absolutely. And we were interested in looking at how COVID-19
specific therapies varied by race ethnicity. And of course,
things have changed dramatically in this area. As an example,
Hydroxychloroquine was the most frequently used drug, and we know
we don't use that right now in practice because it's not
recommended. However, and Remdesivir is one of those drugs that
does have fairly good evidence to use. And we saw that less than
10% of patients in our registry were on Remdesivir during the
study period, with black patients being the least likely to be on
this drug. Part of this may be explained by the lower rates of
clinical trial participation among these patients, and then the
other may be just higher rates of comorbidities. But again, might
preclude the use of this drug. And we actually have a paper
coming out from our registry, exactly looking at the differences
in clinical trial participation by race and ethnicity.


Dr. Amit Khera:


Well, certainly look forward to seeing that. I think that would
be an important followup to this. So I guess, leaving you the
last word. This was I think a really important finding, helping
us understand where the problem is, if you will. Actually there's
numerous problems, but your point about upstream focus. So what's
next? What do we do next in this field in terms of helping
eliminate these disparities that we're seeing in COVID-19?


Dr. Fatima Rodriguez:


Yes, our hope when we started this registry is that we would have
nothing to say at this point, this far along in the pandemic. I
will also say one point that we didn't discuss is that mortality
was high, and it was high among all groups. So we still have work
to do in the inpatient setting to lower mortality, especially as
the pandemic continues. But again, our work really suggests that
we need to move upstream and focus specifically on vulnerable and
marginalized communities, such as racial ethnic minorities to try
to prevent the high rates of COVID-19 infection, and in
particular high rates of severe COVID-19 infection.


Dr. Amit Khera:


Well, that was a fantastic review. And congratulations again on
this leg-breaking science at the AHA sessions and one of the
first early manuscripts coming out of the AHA COVID-19 registry.
So thank you again, Dr. Rodriguez. It was a true pleasure to have
you on today.


Dr. Fatima Rodriguez:


Thank you so much, Amit.


Dr. Amit Khera:


And now for our second featured article, we have Dr. Nicholas
Hendren, who's chief cardiology fellow at UT Southwestern Medical
Center and Dr. Justin Grodin, who is an assistant professor in
the heart failure transplant section at UT Southwestern Medical
Center. Their articles entitled Association of Body Mass Index
and Age With Morbidity and Mortality in Patients Hospitalized
With COVID-19, also from the AHA registry and also a late breaker
at the AHA scientific sessions. Welcome gentlemen, and
congratulations to you both.


Dr. Justin Grodin:


Thank you.


Dr. Nicholas Hendren:


Thank you.


Dr. Amit Khera:


Well, I'm going to jump right in, this obviously was a really
exciting article. One, because of course it's timely with COVID.
Secondly because it's one of the first science outputs from this
AHA COVID registry, so we're all very excited about it. And
importantly, really impactful findings I felt. So maybe I'll
start with you, Justin. Tell us out of all the different
questions and people were working on this registry, how did this
sort of move to the top? What was the impetus behind this
question?


Dr. Justin Grodin:


Well, I mean, I think the answer really lies from clinical
experience. I think as you know, Amit, and as Nick knows, we
quickly understood as the pandemic evolved that in addition to
what we would call more traditional risk factors like
cardiovascular disease, diabetes, hypertension, et cetera, and
old age, we noticed that the young individuals that were
hospitalized with this disease were actually more likely to be
overweight or obese in comparison with their older counterparts.
So really based on those empiric clinical observations we
hypothesized that that would certainly influence outcomes for
those that are in the hospital or ill enough to be in the
hospital with this disease. As most COVID research has gone,
we're basing kind of a hypothesis based on pure clinical
assertion. So that was really, the origin was very organic and
really based at observations made at the bedside.


Dr. Amit Khera:


I think that makes a lot of sense, and as you pointed out, with
COVID drinking from the fire hose initially and hearing a lot of
reports about interplay of obesity. But I think the value here of
the registry was which was systematic curation and acquisition of
patient data. So definitely makes a lot of sense why you pursued
this. And I think what you found first and foremost was that the
prevalence of obesity was higher in your patients hospitalized
with COVID than those from exchange of the U.S. population. And
then I'll turn to you, Nick. Tell us a little about what you all
discovered, what happened with these folks with obesity? What was
the course? What were some of the findings?


Dr. Nicholas Hendren:


You know, as Dr. Grodin mentioned, we were really interested at
the intersection between the obesity epidemic and the COVID-19
pandemic. And they're major questions focused on two parts
initially, which is, are people who are obese at increased risk
of dying in the hospital? And the second part being, if you're
hospitalized and obese, are you more likely to be intubated? And
the answer to both of those after adjusting for the traditional
risk factors like age, renal function, et cetera, were yes. And
so what we observed was that people who are younger than 50 and
severely obese, that means a BMI greater than 40, were at
increased risk of dying. And that includes young people who
otherwise might not think that they were high risk of dying. And
then we observed that your body mass index, if you're obese,
again a BMI greater than 30, puts you at increased risk of ending
up on the ventilator unfortunately.


Dr. Amit Khera:


So really I'm going to dig deeper here as you all did in this
paper. At first, obviously the prevalence of obesity was higher.
Secondly, as you pointed out certain complications like being on
the ventilator and I think VTE and other complications, and then
some really interesting finding was this interaction with age.
Maybe, Nick, tell us a little bit more about that age
interaction.


Dr. Nicholas Hendren:


I think a lot of people are familiar with that age is one of the
strongest, if not the strongest risk factor for dying from
COVID-19. And what we were interested in was, if you adjust for
age and try and take away the association between age, what is
the risk of obesity in and of itself? And so we looked at
patients that were less than or equal to 50 years old, kind of 51
to 70 and older than 70 years old. And really wanted to look at
for those individuals that are obese in those age groups, what
are their outcomes? What is their risk? And what we observed was
that if you're older than 70 and obese, your risk of dying is
probably not all that different by BMI. But if you're younger
than 50 and obese, your risk is significantly higher if you're
obese than if you were normal weight for that age group.


Dr. Amit Khera:


It's pretty fascinating this age interaction, that obesity seem
to be more of a bad actor, if you will, in young people than it
was an older people. And Justin, why do you think you find that?
What was the rationale or biology there?


Dr. Justin Grodin:


You know, Amit, I think that's a great question. And that's a
question that we were asking ourselves. As with other diseases,
individuals that are more obese tend to be younger in general. So
it's very unusual to see somebody that's older that is otherwise
obese. So we do see a little bit of an imbalance in the age
distribution, favoring higher obese groups in those that are
younger. And that certainly could have influenced some of the
observations that we saw. And then I think what's perhaps more
interesting is, really what makes these young people that we
would otherwise think would be low risk, high risk? What is it
about obesity that portends a higher risk with COVID-19?


Dr. Justin Grodin:


And Nick and I, we speculated in the manuscript and really the
reasons are threefold. At least we think, obviously it could be
more than that. But number one is that we all know that obesity
can be associated with metabolic diseases, diabetes, and whether
or not there's some subclinical or undiagnosed form of that that
is also contributing to risk in these people mediated by obesity
could be one possibility.


Dr. Justin Grodin:


The second is actually directly related to the SARS-CoV-2 virus
itself in that the ACE2 receptor is actually abundantly expressed
in adipocytes. And so we know that obese individuals have more
adiposity perhaps putting them at higher risk. And then the third
reason is that individuals that are more obese actually have just
more mass on their thorax and that might influence some of their
pulmonary dynamics and might put them at increased risk for
adverse events.


Dr. Amit Khera:


All certainly great hypotheses, and obviously further things to
test. I'm looking at your conclusions and essentially you
reminded us that preventive strategies in obese people regardless
of age is something we need to focus on. So I think that's a
really important take home point. Last question. Do you, Nick, I
want to first congratulate you. I know way back when we were just
thinking about the problem of COVID and begin to collect our own
data and that germ of an idea really snowballed into this idea of
the AHA COVID registry, and you had a critical role in that. I
remember talking to you and you were putting in data on nights
and weekends. How does it feel now to see the output of your work
really so quickly and so such impactful work after doing all this
labor and working so hard to get this up and running?


Dr. Nicholas Hendren:


Well, I think anytime you're able to have at least a small amount
of success or something that's felt to be valuable to the
contributions, it's always a nice thing. And it was such a team
effort all the way through and from the American Heart
Association to our attendings, Dr. de Lemos who spoke earlier and
Dr. Grodin and all of our team members. And so it's really
impressive how the entire field of medicine and cardiology has
come together and try and battle COVID across all lines. And so
to contribute to that in even a small way is hopefully helpful.
And hopefully people will read our information and make choices
that will help keep them safe and keep people out of the hospital
and doing well off the ventilators.


Dr. Amit Khera:


Well, thank you. And congratulations to you both on a really
fantastic work and impactful paper. And that's it for me, I'm
Amit Khera, digital strategies editor for Circulation covering
for Carolyn Lam and Greg Hundley, who you'll hear from next week.
Thank you all for enjoying our podcast today.


Dr. Amit Khera:


This program is copyright of the American Heart Association 2021.