Will Vaccines Work Against the New Variants? Virologist Dr. Angela Rasmussen on Unraveling the COVID Mysteries

Dr. Angela Rasmussen

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Marianne O’Hare: Welcome to Conversations on Health Care with Mark Masselli and
Margaret Flinter, a show where we speak to the top thought leaders
in health innovation, health policy, care delivery, and the great minds
who are shaping the hea lth ca re of the future.

This week , Mark and Margaret speak with Dr. A ngela Rasmussen, who
leads the Core V irology team at the Center for Global Health Science
and S ecurity at Georgetown University Medical Center. She's an
expert on emergent pathogens like Ebola , MERS and now SARS CoV - 2,
COVID - 19. She's a leading expert on what drives the expression of
viruses in humans, and talks about the importance of masking and
getting vaccinat ed .

Lori Robertson also checks in . The Managing Editor of Fact C heck .org
looks at mi sstatements spoken about health policy in the public
domain , separating the fake from the facts. And we end with a bright
idea that's improving health and wellbeing in everyday lives.

If you have comments, please email us at [email protected] , or find
us on Facebook, Twitter, or wherever you listen to podcast s . And y ou
can also he a r us by asking Alexa to play the program Conversations on
Health Care. Now , stay tuned for our interview with Dr. Angela
Rasmussen here o n Conversations on Health Care .

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Mark Masselli: We're speaking today with Dr. Angela Rasmussen , who leads the core
virology team at the Center for Globa l Health Science and Security a t
Georgetown University Medical Center. Her global renowned team
c enters on emerging pathogens like Ebola , MERS, and now SARS CoV -
2 or COVID - 19 , focusing on genetic and other factors that drive severe
infection in humans.

Margaret Flinter : Dr. Rasmussen is a frequent contributor across the media landscape
on the science behind COVID - 19 , f rom the effectiveness of mask use
and vaccines and also the threat of emerging variants. She also serves
on the NIH Advisory Committee on changing the culture to end sexual
harassment. Her work has been published in numerous journals
incl uding [inaudible 00:02:02] and the New England Journal of
Medicine. Dr. Rasmussen, we welcome you to Conversations on
Health Care today.

Dr. Rasmussen : Thank you so much for having me.

Mark Masselli : Unfortunately, we have this grim milestone that the US r eported this
week , more than 400,000 Americans have died from COV ID - 19 since
the pandemic began. T he Novel Corona v irus, as it was first known ,
sent the global scientific community really into overdrive, trying to

Dr. Angela Rasmussen

develop a consensus on what the pathogen wa s and how to contain it.
We've learned so much so quickly. I'm wondering if you c ould share
with our listeners h ow formidable foe is COVID - 19 a nd where do you
think we are in terms of the pandemic ’ s trajectory .

Dr. Rasmussen: Well, you know, one of the thi ngs that I think myself and a lot of my
colleagues were thinking about when the news that this was a
Corona v irus first came out about a year ago, was how much it was
going to be like SARS classic or MERS Corona v irus. And this virus is
different actually in two key ways , o ne good and one bad. The good
part is that this certainly has a much lower case fatality rate than
either SARS Coronavirus, or MERS Coronavirus. So that's excellent
news. But the bad news is th at it's much more transmissible . Unlike
SARS cl assic, it can be transmitted and transmitted very effectively
during the pre - symptomatic period.

Unfortunately, because we responded with really half measures such
as travel bans, rather than focusing on increasing our testing and
tracing capacity that wou ld have allowed us to control this from the
beginning , r ight now where we're at is a situation of uncontrolled
community transmission throughout most of the US and in other
parts of the world. And that means that people don't know when
they're being expose d, they don't know that they're at risk potentially,
of transmitting it to others , a nd that has compounded as it has spread
through the population. But I think that the good news for the future
of the pandemic is that now we do have vaccines that have exce eded
our wildest expectations in terms of their efficacy. So really, now it's a
race against the clock to see how quickly we can get as many people
vaccinated as quickly as possible .

Margaret Flinter : You know, Dr. Rasmussen, one of the more confounding th ings about
the virus is that the way it seems to just you know deal a light blow, a
glancing blow to many who become infected and yet send others into
what we call the cytokine storms with very rapid decline. You have
long studied the drivers of P athogenic ity of viruses. When we look at
the collective science that we now can agree on , as well as your own
research , w hat do you think are the most important drivers of both
infection and severe disease with COVID - 19?

Dr. Rasmussen: Well, I can tell you from a m olecular perspective, I think that what you
just mentioned , whether a person goes into a cytokine storm or not is
clearly one of the most important factors in driving COVID - 19 severity,
and that probably has something to do with the speed and the
robustnes s at which a person can mount an effective innate immune
response. So we've seen that people who have more severe disease
outcomes tend to have diminished interferon response. An interferon
is sort of like a fire alarm and a sprinkler system all in one . It will
detect that there's a viral infection there , a nd then it will begin

Dr. Angela Rasmussen

secreting cytokines . When that doesn't happen at first , t hat results in
a less effective adaptive immune response , a nd that also results in
essentially uncontrolled inflammation. Wha t we still don't really know
is what predisposes a person to have that delayed response. It's
certainly genetic . It probably also has a lot to do with epigenetics ,
probably also has a lot to do with other comorbidities, potentially
even diet and environmen tal factors. So it's really c omplicated. We
can model this a nd that is something that I'm working on , something
many of my colleagues are working on , trying to look at that using
animal models , b ut ultimately we still don't really have a very good
idea abo ut what predispose s a person to have those types of
responses that cause severe illness.

Mark Masselli: Dr. Rasmussen, you know, we've had a numbe r of guests on over the
years. O ver this last year, Dr. Fauci has been on a couple of times .
People are focuse d in on this mutation or this new strain, the UK
variant that's come up. I think we've heard from him and maybe
others that Coronaviruses , they're going to mutate, they're going to
do things , and I'm wondering what's your sense of this variant.

Dr. Rasmuss en: So this is still very much an ongoing area of research, but the
epidemiological evidence does suggest that both the B117 UK variant,
as well as the 501 Y . V 2 variant from South Africa, and the P1 variant
from Brazil, are all more transmissible. And that' s largely based on
epidemiological evidence that those variants rapidly became
dominant, suggesting that they had some sort of advantage to
outcompete other variants. We do expect variants to emerge , a nd it's
not unreasonable to expect that variants would emerge that are more
efficient at infecting a human host, because that's really what a virus
i s driven to do evolutionarily. In terms of immunity, I mean, that's
really the million dollar question right now, we really do need to know
how well vaccines are going to work against these , and new preprints
came out suggesting that while the B117 variant doesn't appear to be
a problem in terms of the vaccine, the mutations in the 501Y.V2
variant from South Africa, are another story , a nd we should be
concerned bec ause several of these mutations have been shown to
reduce antibody neutralization. So antibodies do not neutralize it as
well .

B ut the good news here is that when you have serum from somebody
who's been vaccinated, they're making antibodies for the entire spike
protein. And the same study that showed that those particular
mutations resulted in a loss of neutralization , were still effectively
neutralized by vaccinated sera. So , the serum from people, the
totality of the antibodies that they made against the spike protein in
the vaccine, were still capable of neutralizing at least pseudoviruses
that contain ed that spike protein. So that suggests that overall, the
antibodies are generating a response that's still protective. The

Dr. Angela Rasmussen

bottom line here is that vaccine s should probably still work against
these new variants , b ut we do need to do more genomic surveillance
to see other variants that might emerge in the future, especially as
more people get vaccinated, and there's going to be increased
selection pressure on the virus to mutate further. Again, we need to
vaccinate as many people as possible and keep looking at the virus to
make sure we don't need to adjust the vaccines in the future.

Margaret Flinter: Well, we have seen the arrival of the vaccines . The speed at which
they were developed, the safety testing with which they were
developed is really one of the few bright spots in this pandemic . There
is s t ill a lot of vaccine hesitancy. Give us what you use a s your best
both scientific and layperson argument for why the vaccine really is
both safe and effective as we're trying to communicate this message
out to people and get them to take advantage of the fact th at the
vaccines are here today .

Dr. Rasmussen : There are a lot of different reasons, many of them justi fied for being
hesitant to take these vaccines. I start usually by reminding people
that these vaccines , and the speed at which they were developed , and
their efficacy is really one of the greatest scientific achievements of
my lifetime , and w e should real ly regard it as that. I think it's really
important that we engage with people with what their actual
concerns are, and we should do so seriously. V accine hesitancy can be
associated with these more extreme views , a nd often with people
who are not going to be convinced that vaccines are safe or effective
no matter what you say to them . I think we need to stop approaching
vaccine hesitancy as if all people are coming from that space , b ecause
I think many people who are concerned about the vaccines really do
have legitimate concerns. And for example, people want to know if
these vacci nes were developed so quickly , a nd this pipeline normally
takes years and years or even decades, then how do we know that
these vaccines actually do work and are safe .

And we norm ally develop vaccines as a sequential process . We start
by spending a couple years designing the vaccine, then we spend a
couple more years testing it o n animals, then we spen d a c ouple more
years doing Phase I , II trials, then we finally spend a couple mo re
years after that doing phase III trials that usually go for a lot longer,
because we're also looking at vaccine durability. In this case, we did
many of those things at the same time. So the vaccines that are ahead
in the race, the ones that already hav e authorization , are vaccines
that can be designed using computers. W e already had some data
suggesting that mRNA vaccines are safe from other phase I trials that
had been done before the pandemic , s o we were able to move right
into phase I clinical trials while doing the preclinical animal studies at
the same time. Now, the phase III part of the process was done in a
more rapid period of time because we decided not to look at

Dr. Angela Rasmussen

durability , a nd that's really the one thing that's been sacrificed. So we
still u sed tens of thousands of patients, the trial sizes for the phase III
trials were the same, we just didn't look at durability, but that's still
going to be looked at long term.

But the number of people that we looked at in the phase III trials is
comparable a nd that allows us to look at safety, at least short term
safety very effectively . We didn't really sacrifice anything. And using
symptomatic COVID - 19 as an endpoint for the trial rather than looking
at something like infection, that maybe harder to measu re in
asymptomatic people , allowed us to get efficacy data very quickly.
Now, that's not the only form of vaccine hesitancy . Others are
concerned about whether the vaccine is going to be safe for certain
subgroups of people, and in particular communities o f color , b ecause
historically, those communities have been terribly exploited by
biomedical researchers , a nd in addition to that, actually I think that
those communities are disproportionately affected by the pandemic
because of disparities that exist due to racism.

So I think that it's really important also to engage very seriously with
those concerns, and in many cases, to have trusted messengers. So ,
people from their own communities, as well as physicians from within
those communities communicating exac tly why those vaccines are
more important for the higher risk communities to be taking than not ,
a nd th at ultimately these vaccines save lives. And some people are
just saying, w ell, I'd rather wait and see. And sort of by necessity,
most people are going to have to wait and see because we don't have
a sufficient supply to vaccinate everybody on demand right now.
What we really need to be thinking about right now at this moment, is
how we're going to improve distribution . To give the vaccine to
everybody wh o wants it and everybody who needs it w e need to be
thinking about all of these things , b ut we also need to be thinking
about what is the most urgent problem facing us right now , a nd that
is vaccine distribution and supply.

Mark Masselli: We're speaking to day with Dr. Angela Rasmussen, who leads the
virology team at the Center for Global Health Science and S ecurity at
th
Georgetown University. Well, we have the 46 President who has
been inaugurated , a nd really he's called for a huge public health
interventio n. But we also have wearing mask , f or those who are
hesitant , we remind them wearing masks, social distancing, and
avoiding large crowds is very important. But I want to get back to the
virus itself. It seems to me that it's finding ways to survive, and th at
we've got to have more clinical trials that are going on . Talk about
what other things are happening in the background , b ecause I would
assume that we want to do other types of trials, not only on vaccines,
but we also want to look at all t hese others . Who's leading that ?
W h ere in the scientific community t hey're saying, hey wait, we need

Dr. Angela Rasmussen

to start running some parallel studies to look at opportuniti es that
might be in front of us?

Dr. Rasmussen: Well, ultimately, when it comes down to testing products, w hether
they be vaccines or therapeutics, academic institutions are not
capable of making a product that will be sold on the market . T hey
don't have the manufacturing capacity, they don't have the regulatory
resources, things like that. So ultimately, if yo u're talking about
something that's going to be used for the public, unless it's something
like convalescent plasma, that's not really a pharmaceutical product,
you're really talking about making sure that you are partnering with a
pharmaceutical company. But you know, there are plenty of academic
institutions that are running trials with existing drugs, using things like
back when we were all talking about H ydroxychloroquine, a number
of different academic institutions were running clinical trials with tha t,
because it's an already available existing generic drug , a nd in that
context, you're just using something that's already there a nd so you
can test it out in your own medical center.

F or new vaccines, all of them have a pharmaceutical partner, because
th ey will certainly need somebody to manufacture and distribute that
vaccine, as well as to seek FDA approval, which is a very expensive
and cumbersome process. Around the world though , there are
numerous trials going on for both novel therapeutics and makin g new
vaccines, you know, many vaccines that are at different places in the
development pipeline . I think the last time I checked the tracker there
were over 300 different vaccine candidates. Some will only be
available in certain countries , and so this is where organizations like
the World Health Organization come into this. That is something that
hasn't gotten as much coverage here in the US , just because our prior
President expressed intentions to withdraw from the World Health
Organization and did not p articipate in the Covax Group, which is a
consortium of countries led by the WHO, by CEPI, and GAVI which are
t w o vaccine organizations to develop vaccines and manufacture and
supply them to the entire world. And this is something we need to be
thinking ab out long term.

It's not necessarily developing new vaccines, but it's figuring out how
we can take the vaccine supply that we have, get it from countries,
wealthy countries like the United States, and make sure that they're
being eq uitably distributed worl dwide. B ecause especially in places
that don't have as much health care infrastructure, low and middle
income countries that may not be able to purchase millions and
millions of vaccine doses, it's going to be absolutely critical that we
still find a way t o get vaccines to all the people in those countries.
Because this is a pandemic and by definition, it's affecting the entire
world, this isn't going to be over once we reach the herd immunity
threshold in the United States . This will only be over when we r each

Dr. Angela Rasmussen

the herd immunity threshold globally. So that I think is something that
I'm hopeful that the new Biden administration will be more involved
in, is really working with international partners collaboratively to
make sure that everybody in the world can have access to these
vaccines, because until all of us are safe, none of us are safe .

Margaret Flinter: You know, Dr. Rasmussen, I'd be curious for your thoughts on w hat
we've learned, right ? I think back to the days in New York last spring,
and your heart just goes out to all of our clinical colleagues who had
so little tools to work with . You know, aside from all the worries about
PPE and so forth , w e just didn't know a lot about how to treat this.
And my guess is that we have learned some very important things
about how to treat cytokine storm and how to treat other
overwhelming viral infections like that. And I wonder if you could, it's
kind of a complicated question again, but both comment on what
we've learned about the care of the individual , and what we've
learned about what we need to do as a public health community
whenever a new threat like this arises down the road. Can you t ry and
talk about at least one of the two ?

Dr. Rasmussen : Yeah, I can try to tackle that in general. And it's probably going to
have to be the latter question about preparedness, because I'm not a
physician , I don't treat patients , a nd the only thing I can say about
that is that it's clear from talking to my colleagues who are physicians,
respiratory therapists, nurses, who are treating patients that we have
come far in how we treat people who have severe COVID at least , b ut
really, we don't have a lot of really good targeted strategies . O u r
antiviral drugs are only really effective. They're kind of effective, but
they have to b e given as early as possible , a nd given that they're all
delivered by IV infusion i t can be very difficult to do that at the time of
diagnosis. We also don't have a sufficient supply to be treating
everybody who tests positive for SARS Coronavirus - 2 with t herapeutic
monoclonal antibodies, for example. So, you know, that has been sort
of -- it's been a disappointment that we don't have better antiviral
therapeutics.

In terms of treating the cytokine storm, a lot of the clinical trials for
existing drugs tha t target specific cytokines, such as Tocilizumab,
which targets IL - 6 , which is a major pro - inflammatory cytokine , have
really been also disappointing . They've really showed no effect or
therapeutic benefit. The only thing that has , is a really old drug , b u t
that's also a very, very potent broad spectrum anti - inflammatory
steroid a nd that's Dexamethasone treatment, which does have a
significant mortality benefit, at least for patients receiving
supplemental oxygen. So we've come a little ways, but we still h ave a
long way to go, I think , in terms of translating what we know about
the pathogenesis of COVID - 19 into treatments that will be useful in
the clinic and will be available to a lot of people who need them. I

Dr. Angela Rasmussen

think though, that in general, for public hea lth and being prepared for
other pandemics, that that will happen, because it's not a question of
if , but a question of when . T here are thousands of other circulating
Coronavirus es alone. Plus , there are 24 other families of viruses that
can also have the potential to be human pathogens. And in a sense,
we should count ourselves lucky that something like this emerged
instead of som ething like a more transmissible N ipah virus, for
example, that has a much higher fatality rate.

So, we need to be pre pared thou gh, for that disease X to emerge in
the future , a nd that means basically increasing our investment in
research across the board. And that's everything from basic research,
surveillance, basic virology to understand better how these viruses
work s o we can t ry to find some of their weak spots, all the way up to
translational things, looking at new vaccine platforms that could be
used to generate new vaccines against a novel pathogen very rapidly.
Things like, you know, how would we potentially take mRNA vacci nes
for example, and be able to start manufacturing them right away
without necessarily needing to do a phase III clinical trial . How would
we be able to speed up the process?

And I think the vaccine operation warp speed, the expedited vaccine
review proce ss, does give us a starting point at least for removing
some of the regulatory roadblocks and red tape that sometimes get in
the way of this. But ultimately, I mean, I think you can ’t always fix
problems by throwing money at them , b ut you also can't do
mea ningful research if you don't have funding to support it. And
historically , with Coronavirus es anyways, but many other emerging
viruses, when there is an epidemic of a novel emerging virus, and this
is true for SARS, for MERS a nd I hope it won't be th e cas e for SARS - 2 ,
t here's an immediate influx of funding as people are paying attention
to the crisis. And so people drop everything and start working on
these viruses , a nd then that money goes away , so they can't renew
their grants. Any research they were con ducting on the virus will stop
because they can't afford to keep doing it.

We really need to stop funding scientific research , especially that has
important pandemic preparedness implications with this boom and
bust cycle of funding. If we really want to b e prepared for the next
pandemic, we need to make sure that we're doing the research
before that virus emerges and not scrambling to find out about it
afterwards. And that means that we're going to have to make a
significant investment without an expectati on of a payoff because
that's the irony of pandemic preparedness research. If you're actually
succeeding at it, then it looks like you're not doing anything becaus e
there's no new pandemic. So I would hope that people , as they're
more interested in science and viruses in general, which is a
wonderful silver lining anyways of this pandemic for me , I hope that

Dr. Angela Rasmussen

people will also remember this for some time to come and
understand why we need to put more effort into preparedness
measures like this.

Mark Masselli: We've been speaking today with renowned virologist Dr. Angela
Rasmussen at the Center for Global Health Science and Security at
Georgetown University. You can access her many published papers
and articles by go ing to www.angelarasmussen.org , o r you can follow
her on Twitter at @angie_rasmussen . Dr. Rasmussen, thank you so
much for your tenacious efforts of your own and of your colleagues in
uncovering the secrets of all these deadly global pathogens, your
inn ate gift to making it understandable , a n d also for joining us today
on Conversations on Health C are.

Dr. Rasmussen: Thank you.

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Mark Masselli: At Conversations on Health Care, we want our audience to be truly in
the know when it comes to the facts a bout health care reform and
policy. Lori Robertson is an award - winning journalist and Managing
Editor of FactCheck.org, a nonpartisan, nonprofit consumer advocate
for voters that aim to reduce the level of deception in U.S. politics.
Lori, what have you go t for us this week?

Lori Robertson: Two COVID - 19 vaccines are now authorized in the US by the Food and
Drug Administration , o ne vaccine from Pfizer and BioNTech , and
another from Moderna. We'll take a look at how these vaccines work.
Both the Pfizer BioNTe ch and Moderna vaccines are mRNA vaccines
that require two doses. The vaccines work by triggering an immune
response against the spike protein of the SARS C oV - 2 virus. That spike
protein sits on the surface of the Coronavirus and is what the virus
uses to enter cells. The vaccines are made of modified messenger
RNA , or mRNA, wrapped in a special blend of fatty molecules known
as lipid nanoparticles. The mRNA provides instructions for cells to
make their own spike proteins, prompting the body to generate
pro tective antibodies and activate T cells. The lipids help deliver the
RNA into cells and prevent it from being degraded too quickly. As the
Centers for Disease Control and Prevention has explained, there is no
way to catch COVID - 19 from this type of vaccine because the vaccine
is not made of a virus. And because the mRNA from the vacc ine
doesn't enter the nucleus, t he part of the cell that houses DNA, it
‘does not affect or interact with a person's DNA.’ contrary to some
online rumors. A nd that's my fa c t che ck for this week. I'm Lori
Robertson, Managing Editor of Fact C heck .org.

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Margaret Flinter: FactCheck.org is committed to factual accuracy from the country’s

Dr. Angela Rasmussen

major political players and is a project of the Annenberg Public Policy
Center at the Univer sity of Pennsylvania. If you have a fact that you’d
like check ed , email us at www.chcradio.com . We’ll have
FactCheck.org’s Lori Robertson check it out for you here on
Conversations on Health Care.

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Mark Masse lli : Each week , Conversation highlights a bright idea about how to make
wellness a part of our communities and everyday lives.

Over the past few decades, kids have been getting less and less
physical activity t hroughout the school day . The University of
Mi chigan researchers wanted to find a creative and effective solution
that would increase kids’ movement without disrupting the school
day.

Dr. Rebecca Hasson: We looked at the scient ific literature in terms of pro long ed sitting,
and they have demonstrated t hat if you just do two minutes of
activity, a small burst , get up , do some movement , sit back down ,
a ctivity in that small of a dose can have dramatic improvements on
health , on cognition , on learning. So we decided to develop an
intervention , a program th at would allow children to get these small
bursts of activity throughout the day.

Mark Masselli: Dr. Rebecca Hasson is principal investigator for InPACT - Interruption
of Prolonged Sitting with Activity. She wanted to find out if just two to
three minute s hort bursts of physical activity five times a day would
impact the kids’ cumulative movement.

Dr. Rebecca Hasson: We typically see in PE or recess lower participation in girls compared
to boys, but in classroom activity breaks you actually see similar rate s
of participation. We also saw that for children who are carrying a few
extra pounds , that those children also were exercising at a high
intensity.

Mark Masselli: Dr. Hasson said they wanted to design the intervention that would be
easy for teachers to ad opt and manage. So they created videos
desig ned to get kids moving quickly.

Dr. Rebecca Hasson: We created a compendium of 200 activity breaks that are just three
minutes long. So the teachers had a variety of different types of
activities, whether it was jumping jacks, something that will get their
heart rate in a target heart zone .

Mark Masselli: K ids burned on average about 150 more calories per day , had accrued
a significan t amount of physical activity. A low cost , easily adoptable
fitness intervention for kids, allowing short bursts of physical activity
throughout the school day, empowering kids to move more positively
impacting the learning experience , n ow that's a bright idea.

Dr. Angela Rasmussen
[Music]
Mark Masselli: You've been listening to Conversations on Health Car e. I'm Mark
Masselli.
Margaret Flinter: And I'm Margaret Flinter.
Mark Masselli: Peace and Health.
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Marianne O’Hare: Conversations on Health Care is recorded at WESU at Wesleyan
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