Long COVID: Skeptics Are Wrong, Researchers Say

Akiko Iwasaki and Fiona Lowenstein on Long COVID

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Marianne O’Hare: Welcome to Conversations on Health Care. This week , we look at the
growing public health threat of Long COVID with renowned Yale
researcher Akiko Iwa saki on her nasal vaccine work.

Akiko Iwasaki: I wish we had a warp speed like eff ort to be able to deliver this to
people as soon as possible, but we don't have that kind of support
right now .

Marianne O’Hare: And Patient Advocate Fiona Lowenstein and her new book, The Long
COVID Survival Guide . Fact C heck.org ’s Managing Editor Lori
Rob erston checks in and we end with the bright ide a improving
everyday lives. Now, here are your hosts Mar k Maselli and Margaret
Flinter.

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Mark Masselli: The Center for Disease Control and Prevention reports that 1 in 13
adults in the United States has COVID symptoms that last at least
three months after they initially came down with the virus. Millions of
Americans say they are affected, even Virginia Senator Tim Kaine, but
questions remain with critics of Long COVID saying correlation is not
causation and suggesting other issues are at play.

Margaret Flinter: Joining us to discuss Long COVID is Akiko Iwasaki who is a Sterling
Professor of Immuno biology and Molecular Cellular and
Developmental Biology at Yale University. Also with us is Fiona
Lowenstein , Editor of the Long COVID Survival Guide, How to Take
Care of Yourself and What Comes Next ! It's a book that focuses on
stories and advice from 20 COVID Long callers as well as from experts.

Mark Masselli: Welcome to both of you to Conversations on Health Care . Let's begin
with you , Akiko. I wonder if you could share with us what we really
mean when we say Long COVID. What's the definition you are using?

Akiko Iwasaki: Right , so Long COVID is a definitely a condition that is heterogeneous
and variable and it's difficult to pinpoint because we don't have a
biomarker, but it's essentially a disease that happens after the acute
phase of COVID that lingers over four weeks from the starting of the
acute phase , and in some people, it's lasting for over two years now ,
and it contains multiple different symptoms, over 200 different
symptoms have been reported, involving pretty much every organ
system. As I said, it's a heterogeneous disease that requires more
investigation.

Margaret Flinter: Well, Fiona, let me turn to you , doctors diagnosed you very early in
the pandemic with COVID and you were hospitalized in March of
2020, which really was the very early days . You recently wrote that
you're dealing now with Long COVID symptoms, but they're milder

Akiko Iwasaki and Fiona Lowenstein on Long COVID

than most . Share with us, if you will, what you'd like to about your
personal story with Long COVID.

Fiona Lowenstein: You know, I think one of the most important takeaways from my
personal story is that privilege and access that I had as a white
economically privileged, N ew Yorker with a primary care provider who
knew me well, played a huge part in my getti ng that initial COVID
diagnosis, that test the care when I needed to be hospitalized.
Eventually , of course, understanding that what I was going through
were most likely post viral sequelae and so it's been important to me
to share my story as a way of sort of normalizing this experience , but
also, of course, because I had that positive test and kind of that that
marker that did essentially prove that initial COVID infect ion . The
symptoms that I deal with today are definitely on the milder end of
the spectrum . It's crucial to understand that there are people with
Long COVID who are bedridden right now , who are not able to leave
their homes, you know, there are folks who ar e using mobility aids to
get around and people who are also deteriorating and not making
progress in their recoveries, although there are people who like
myself have experienced some level of improvement . I credit a lot of
my recovery to my ability to take time off from work and rest and
pace , and again, none of that would have been possible, had I , you
know, had children that I needed to care for, had I not had flexibility
in terms of my financial situation and my work. Unfortunately , that's
just not the r eality for a lot of patients and not the reality for many of
the patients who wrote chapters in our book.

Mark Masselli: Well, Fiona, thank you so much for sharin g your story and your
insights. Akiko, we recently had the Assistant Secretary of Health,
Rach el Levine as a guest and she unequivocally stated that Long
COVID patients are not “ malingering ,” b ut as there are skeptics. There
was an article in the Journal of the American Medical Association
highlighting data that raised questions about the very exis tence of
Long COVID suggesting that patient's symptoms were in their heads,
and I'm wondering what your observations of that article are.

Akiko Iwasaki: Alr ight . I'm just surprised to see that there are some skeptics that are
still doubting the validity of this disease. We've done a lot of immune
profiling in people with COVID, Long COVID, versus those who
recovered and we're seeing distinct features of immune responses
that are not found in the control groups and so just by immunological
features alone, we can distinguish people with Long COVID and it's
very difficult to just imagine that .

Margaret Flinter: Well, that is such an important message for people to hear and I think
probably very comforting to people with Long COVID. But I want to
pick up on the point about your guide, Fiona, which includes a focus
on what you call medical racism and gaslighting. Indeed , the guide has

Akiko Iwasaki and Fiona Lowenstein on Long COVID

received praise from patient advocates who say they've been ignored
in the past because they're women or gay . You talked about some of
the benefits you appreciated from something of a privileged status in
terms of access to health care and economics , but this is another
whole dimension that can really harm people. What's the lesson here
for the healthcare community?

Fiona Lowenstein: You know, none of these issues are new, right? Unequal access to
health care has been an issue certainly in our society and in our
country for a long time. I think it's important to understand that these
structural barriers were very much here before the p andemic, but
were, of course, exacerbated by the healthcare overwhelm, that
occurred and continues to occur on a seasonal basis when we have
these huge surges, you know, case surges for now, not just COVID , but
of course, we're seeing for flu and RSV as we ll , and so the stories in
our books, we have stories from patients who came from
communities that were disproportionately impacted by those high
case loads of acute COVID, right. We have a patient in our book who
writes about getting sick in the first wave in an urban black
community in Baltimore, and what it was like to try and fight for care
continually. We have a story from a Latina woman in Los Angeles, the
same thing, trying to get doctors to take her seriously. I think for
medical providers and for th ose treating Long COVID, it's important to
understand that some of those patients who don't have that initial
COVID - 19 diagnostic test or may not have that record of being treated
for post COVID symptoms, may have been facing some of those
structural barri ers, you know, medical racism, medical sexism . These
are very real barriers that existed prior to the COVID - 19 pandemic,
but have definitely been exacerbated by just the level of healthcare
need that is going on right now.

Mark Masselli: Akiko, your lab at Yale is partnering with Mt. Sinai Health System in a
very important Long COVID study that's looking at distinguishing
features of Long COVID that you've identified through immune
profiling . I wonder if you could share with us right now about what
you've l earned so far.

Akiko Iwasaki: So , we are collaborating with people from Mount Sinai, especially Dr.
David Putrino’s group, and looking at deep immune profiling in people
with Long COVID comparing that signature to people who recovered
from COVID, as well a s healthy controls who's never had COVID
before. What we're seeing , there are several key features that
distinguished people with Long COVID such as elevated levels of
exhausted T cells. These exhausted T cells are only found in people
who are fighting chr onic infections or cancer T cells that keep seeing
the same antigen over and over , that's where we see these types of
cells. We also see that there's evidence for elevated Epstein - Barr Virus
reactivation in people with Long COVID. Another feature that's ve ry

Akiko Iwasaki and Fiona Lowenstein on Long COVID

uniformly different between Long COVID and control groups is the
lower levels of Cortisol , Plasma Cortisol , we're seeing in Long COVID
patients and because Cortisol is such an important hormone that
regulates so many different aspects of our physiology, we can
basically assign a lot of the symptoms that they're getting with this
low levels of Cortisol .

Margaret Flinter: Well, maybe Akiko, if I could just continue on that path around your
research a little bit, we saw that you're also working with Dr. Har lan
Krumholz at Yale on the LISTEN study, which stands for Listen to
Immune Symptom and Treatment Experiences Now . I wonder if you
could share with us the kind of data you're looking at in this study,
some of the hypothesis you're testing out and what's th e timeline for
making any results note ?

Akiko Iwasaki: Yeah, so the Yale LISTEN Study is with Dr. Harlan Krumholtz, and a
large team of investigators at Yale and what we want to do with this
study is to extend on what we did with Dr. Putrino at Mt. Sinai, and to
really focus on different symptoms. For example, people with Long
COVID as I mentioned have over 200 different symptoms , but some
symptoms are very debilitating such as internal tremors and
vibrations that people can control and that really affects the daily lives
of these people. We want to understand the immune features
associated with these particular symptoms. The other group of people
that we're investigating is post vaccine related long haul. Some people
reporting that a similar symptom to Long COVID can be seen in people
who have gotten the vaccination and we want to understand how
that differs in terms of the immunological features compared to Long
COVID.

Mark Masselli: Fiona, let's stick with a focus on research , and we understand you're a
pa rt of a patient - led research collaborative, that is showing how
you're adding patient voices to the data in the mix . What have you
learn ed so far about making sure that patient voices are part of this
important research?

Fiona Lowenstein: That is a group t hat was born out of the Body Politic support group,
which I started in 2020. So , there are a group of patients with
backgrounds in science and technology and medicine, who basically
started to observe these long term symptoms in real time in their own
bodi es, and in the anecdotes that people were sharing in this online
support group in March and April and in May of 2020 , and they
sought to survey that group , and so essentially did one of the first
surveys that I'm aware of in the United States on long term symptoms
following a COVID - 19 infection and provided us with some of that
statistical data on -- at the time, I think the first survey was just, you
know, a few 100 patients, they've gone on to, of course, work with
much larger groups of patients, and they 're affiliated now with several

Akiko Iwasaki and Fiona Lowenstein on Long COVID

different research institutions , and of course, many of them have
advised the NIH. I've spoken al ongside them to the White House, as
well as the World Health Organization. I think what they're doing is
rea lly powerful, both in the sense, but in many ways, they kind of
raised the alarm on this issue , but they are also really changing the
way that research is done. They are building on what HIV AIDS
advocates referred to as meaningful involvement of patients and
setting researc h agendas and determining what research outcomes
we should be prioritizing, in terms of what we're looking for , and you
know, many of us may be aware of this, but what patients want to see
prioritizing research is not always the same as what ends up gettin g
researched and so that's really what they're trying to do is bridge that
gap and so we have actually a chapter in the book written by Lisa
McCorkle, who's one of the founding members of a patient led
research collaborative, which aims to provide readers with those tools
to understand and navigate emerging research because patients are
doing that they're reading the research online, we want to make sure
that they have the tools to basically understand what they're reading,
that misinformation that they mi g ht see pop up in these support
groups or potentially in media articles.

Margaret Flinter: I think, Mark, you remember we had patient Dave on the show early
on . You know when I look back on 2020 and the beginning of 2021 ,
certainly a happy day in the pandem ic was when the first batch of
vaccines arrived on our door , and the second happy day was when
Paxlovid arrived on our door and we had both a vaccine and we had a
therapeutic treatment and know that this has really helped the
availability of the antivirals has helped reduce the duration and
reduce the risk of Long COVID as well, but Akiko I understand yet
another study is the U . S . Department of Veterans Affairs and the
impact of Paxlovid . So tell us about that research.

Akiko Iwasaki: Sure, so the U . S . Vete rans Affairs study basically looked at people
who've gotten Paxlovid versus those who didn't, but had the same
kind of pre - existing conditions , and essentially what they found was
that people who took Paxlovid had a reduced risk of ultimately
developing Lo ng COVID whereas people without Paxlovid developed
that more frequently. This is a group of people that it's from the
V eterans, so the military population and it may or may not apply to
the general public , but it's an important study that demonstrates that
curving the course of infection and replication of the virus inside the
person could help prevent Long COVID from happening.

Mark Masselli: You've also , Akiko, been doing some groundbreaking work on the
development of a nasal spray vaccine, which research shows would be
more effective at preventing infections. I'm wondering, you know, you
think about Omicron, it continues to mutate. How do you balance
those two ? The nasal vaccine sounds very promising , but on the other

Akiko Iwasaki and Fiona Lowenstein on Long COVID

hand, we continue to see this forever mutating virus out there.

Akiko Iwasaki: Yeah, so the nasal vaccine actually holds some promise in that regard
because it can prevent transmission or at least reduce transmission
between infected people and the more we can prevent transmission,
the less l ikely that the virus has opportunity to continue to mutate
and evolve and so that is why we're really pushing for this nasal
vaccine strategy because having the immune resistance right in your
nose will prevent not only disease within that person, but
tran smission from that person to the next person and that's
ultimately how we need to think about controlling this pandemic is to
provide some sort of herd immunity so that the transmission can be
reduced. Then ultimately, this mutation will not be happening
b ecause we can sort of curtail this spread of the virus throughout the
world.

Mark Masselli: Are we in any clinical trial with the vaccine now ? What can you tell us
about timing and people w ould be very interested in this?

Akiko Iwasaki: Yeah, we are workin g very hard to develop this vaccine so we can do a
clinical trial on humans . We currently don't have enough funding to
be able to make the vaccine that's appropriate for human clinical trial.
We're trying to raise funds through a company called Xanadu Bio and
we're in the midst of fundraising , but it's difficult. I wish we had a
warp speed like effort to be able to deliver this to people, you know,
as soon as possible, but we don't have that kind of support right now.

Mark Masselli: I know that's a very imp ortant issue for scientists that the lack of
funding and we'll keep an eye on Congress during this session to see if
they can move the ball forward.

Margaret Flinter: We hate to think you have to get out and do fundraising for
something that is so desperat ely needed. I did note a few moments
ago, you referenced Epstein - Barr Virus , and we have been reading
about how Long COVID research might help us understand how better
to treat multiple sclerosis or chronic fatigue syndrome , and we're very
intrigued with t hat. I wonder if you could comment on that.

Akiko Iwasaki: COVID is just one of the many pathogens that can cause this
mysterious post acute syndrome. Long COVID is the latest to join that
list, but there are a handful of viruses and bacteria and parasites that
can similarly they cause long term symptoms and many of these
people develop these ME / CFS syndrome. We're hoping that by
studying Long COVID and then we'll be recruiting people with ME / CFS
into future studies with Dr. David Putrino ’s group to be able to
understand the parallel between these diseases, and whether one
research can inform the other because the underlying pathogenesis
may be shared , but that's something that we have to do more
research on .

Akiko Iwasaki and Fiona Lowenstein on Long COVID

Mark Masselli: Fiona, I want to end up with where you started and maybe your best
advice for people and family members dealing with Long COVID. H ow
can they find the best help?

Fiona Lowenstein: Well, the first thing I would say is if you are experiencing or think you
are experiencing Long COVID symptoms , track your symptoms, and
also track your daily activities. I think in the support groups, we found
it really helpful to look at not only when you're experiencing
symptoms, but what might have predated that symptom because a
hallmark symptom of Long COVID tends to be something we call post -
exertional symptom exacerbation the worsening of symptoms
following a period of physical , mental or emotional exertion. So that
can be quite helpful as a starting point. There's a lot of great advice in
this guide . I wou ld say it's a good place to start. Dr. Iwasaki wrote a
beautiful afterward as well, kind of sharing with the reader what the
future of research for this disease might look like , but there's also a
piece of advice that stands out to me right now from Dr. Do na Kim
Murph e y, who is herself both a provider and a Long COVID patient .
She writes that your provider should be your partner in your Long
COVID journey , and that if you are not finding that kind of intellectual
curiosity and partnership in your provider, you deserve to find that
and you should pursue that by whatever means necessary. Obviously,
everyone, you know, we all have limitations in terms of time and
money and access , but I think it's important for patients to feel
empowered and know that that is w hat they deserve and that there
are providers out there like Dr. David Putrino and others who are a
part of this book, who are really committed to forging that
relationship with p atients. There is not a patient - doctor divide on this
issue. A lot of us are really working together , researchers, providers,
patients to solve this collectively , and so we're very grateful to folks
like Dr. Iwasaki and Dr. David Putrino and others who are working
with us to do just that.

Margaret Flinter: Well, let's add Fiona to that list of people working together Congress ,
and we know that Democratic members of Congress have introduced
a number of bills to improve Long COVID research, basically funding
Long COVID research and ensuring that there's access to care for
people who a re suffering and to date, they haven't gotten Republican
support. What are your thoughts on with the patient community and
it really all of us who care about this issue do to make sure that that
funding for research and access is there?

Fiona Lowenstein: W ell, I'd say that, you know, unfortunately, this isn't our first and
likely won't be our last pandemic. I think it's crucial to think about
pandemic preparedness on both you know, in terms of legislation and
on a societal level . Long COVID definitely opene d my eyes up to the
kind of luminal space in between full recovery and illness, and I think
that that's a very important thing to understand, not just for disease

Akiko Iwasaki and Fiona Lowenstein on Long COVID

like COVID, that's a common experience even if you break your ankle,
right . There's not alway s immediate recovery. I think that societally
we tend to be quite uncomfortable with that period of convalescence ,
with chronic illness , with disability , and so even as we move into the
holidays, bringing those conversations out of the shadows, and de -
stig matizing them and talking with your family and friends about what
are your COVID safety measures and understanding that this is a very
personal issue, it's also a collective issue. Unfortunately , it's not
something that's just going to go away, right. We'd like to compare
COVID and the flu . ME / CFS may be related to Long COVID. There are a
lot of people who have been disabled by the flu as well, right . There
are other post viral illnesses . Long COVID is not the first of its kind.
There are ways we can mitiga te these sorts of problems in the future,
and there are ways we can mitigate in the present , and I think talking
about it openly is t he first step to getting there.

Margaret Flinter: Fiona for our listeners, ME / CFS. why don't you say that ?

Fiona Lowenstein : ME / CFS which is the abbreviated term for Myalgic Encephalomyelitis ,
sometimes called Chronic Fatigue Syndrome . It's another often
infection associated complex chronic illness that shares many
similarities with Long COVID. In fact, a large percentage of p eople
living with Long COVID have qualified for the diagnosis ME / CFS .

Margaret Flinter: Thank you.

Mark Masselli: Well, I want to thank you both for joining us. This issue is not going
away , and you really helped our understanding of Long COVID and
what pa tients are experiencing. Thank you to our audience for being
here. You can learn more about Conversations on Health Care and
sign up on our email updates at www.chcradio.com . Akiko and Fiona,
thank you so much for sh edding a lig ht and illuminating this issue.

Akiko Iwasaki: Thank you.

Fiona Lowenstein: 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 about 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 got for us this week?

Lori Rob ertson: Hospitals across the country are seeing a spike of Respiratory
Syncytial Virus infections among children. Experts say the spike in RSV
is most likely caused by an immunity gap created by the lack of
exposure to the virus over the past couple of yea rs. RSV is a common

Akiko Iwasaki and Fiona Lowenstein on Long COVID

respiratory virus that usually causes mild flu like symptoms, but it can
be dangerous for some people, especially older people, infants and
young children. The Centers for Disease Control and Prevention
reported its surveillance systems were showing an increase in RSV
detections and RSV related emergency room visits and
hospitalizations in multiple areas of the country. Each year 58,000 to
80,000 children under five are hospitalized due to RSV infection. Dr.
Paul Offit, a vaccine expert and pediatrician at the Children's Hospital
of Philadelphia told us that this is the worst RSV year at his hospital .
Offit said the restrictions established in 2020 to prevent the spread of
COVID - 19 virtually eliminated other respiratory viruses, creating
what's called an immunity gap and more people are susceptible to
falling ill . RSV, which normally infects nearly all children before the
age of two is highly contagious and spreads when an infected person
coughs or sneezes near other people or through cont aminated
surfaces. People with RSV are usually contagious for three to eight
days , but some infants and immunocompromised people can
continue to spread the v irus for as long as four weeks.

Opponents of the COVID - 19 vaccine are incorrectly suggesting onlin e
that the unusually high number of infections is caused by the pediatric
COVID - 19 vaccines. There's no evidence of that . COVID - 19 vaccination
in the youngest children remains low, less than 8% of children under
five years old have received at least one do se. That rate of vaccination
doesn't account for the spike in RSV cases . Children under six months
of age are at highest risk of hospitalization from RSV and in fact, do
have the highest rates of hospitalization now, and that age group isn't
eligible for a ny COVID - 19 vaccine. That's my fact check for this week.
I'm Lori Robertson, Managing Editor of FactCheck.org.

Margaret Flinter: FactCheck.org is committed to factual accuracy from the country’s
major political players and is a project of the Annenberg Pub lic Policy
Center at the University of Pennsylvania. If you have a fact that you’d
like check, email us at www.chc.radio.com . We’ll have FactCheck.org’s
Lori Robertson check it out for you here on Conversations on H ealth
Care.

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Margaret Flinter: Each week Conversations highlights a bright idea about how to make
wellness a part of our communities and everyday lives. For several
decades, the CDC has been screening new mothers in the postnatal
period for issues t hat could signal a threat to the child's ability to
thrive. The surveillance tool, the Pregnancy Risk Assessment
Monitoring System or PRAMS as it's known, is a population based
surveillance tool designed to identify groups of women and infants at
higher ri sk for future health problems. Dr. Craig Garfield, Founder of
The Family and Child Health Innovations Program at Lurie Children's

Akiko Iwasaki and Fiona Lowenstein on Long COVID

Hospital in Chicago, thought they were leaving out an important part
of the equation, the Dads .

Dr. Craig Garfield: CDC actual ly approached us because they have had for 35 years a
survey of mothers in the perinatal period that gives us really good
data on public health and the public health of mothers as they
transition into motherhood , and they started to get back comments
withi n the survey saying why is the only question that you asked me
about my partner is whether he hit , kick , beat or slap me during
pregnancy. There's so many things that he did that helped me get
through this pregnancy and you don't ask a lot of needles.

Marg aret Flinter: Dr. Garfield, a researcher and pediatrician at Northwestern University
partnered with the CDC and the Georgia Department of Health to
pilot the deployment of a new surveillance tool. PRAMS for Dads ,
which turns out to be a very effective scre ening tool for broader
public health issues as well.

Dr. Craig Garfield: We ask questions about the Dad's physical health, Dad’s mental
health , access to health care , Dad’s use of F amily L eave , Dad’s
[inaudible 00:26:40] with the baby , ideas around breastf eeding
because we know from a pediatric perspective that the chances of
moms successfully breastfeeding have a lot to do with it, if Dad is
supportive of that as well. Then what other risky behaviors that Dads
might be involved in that we need to know from public health
perspective, smoking, drinking, having a gun, those sorts of questions.

Margaret Flinter: Dr. Garfield says identifying issues such as obesity, binge drinking, or
smoking in a father at the time of birth is an excellent time to
empower the n ew father to address those issues impacting not only
his health, but the health of mother and baby as well , and this is a
time when they are more motivated to improve health for their child.

Dr. Craig Garfield: As a pediatrician, I work with a lot of fathe rs , and the fathers I work
with all are looking at the time of birth to really be the best kind of
father they can be , and a lot of that has to do with being able to
maintain their own house so that they are there when their child gets
older, and they can be there to be with them and what used to be
thought of simply to provide for them financially, really is no longer
acceptable to many of the fathers. They want to be there and be
involved in different way than maybe their father or their grandfather
was .

Margaret Flinter: Since launching the pilot PRAMS for dads , Dr. Garfield's team and the
CDC have expanded the program, partnering with several other
states, including Ohio and Massachusetts, and inexpensive easily
deployed surveillance tool, screening new dads for health concerns
that could impact not only their newborns, future health, but their
own health as well, and providing a reliable public health data set for

Akiko Iwasaki and Fiona Lowenstein on Long COVID
individuals, families, clinicians and population health as well. Now
that's a bright idea.
[Music]
Mark Masselli: I'm Mark Masselli.
Margaret Flinter: And I'm Margaret Flinter.
Mark Masselli: Peace and h ealth .
[Music]
Marianne O’Hare: Conversations on Health Care is recorded in the Knowledge and
Technology Center Studios in Middletown, Connectic ut, and is
brought to you by the Community Health Center , now celebrating 50
years of providing quality care to the underser ved, where healthcare
is a right, not a privilege , www.chc1.com and www.chcradio.com .
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