400 Million+ People Globally With Long COVID: A Top Researcher Seeks Solutions

Mark Masselli (00:04)
Our guest is co-director of the comprehensive COVID-19 Center at Northwestern University, which has cared
for nearly 3000 long haulers from 44 states.

Dr. Igor Koralnik (00:16)
Long COVID patient are still there. we see patient in the clinic who had, let's say, seven episode of COVID-19,
and then they picked up long COVID after the third one. There's data being published already out of Canada and
other countries that the more episode of COVID-19 people have the higher the risk.

Margaret (00:37)
Dr. Igor Koralnik brings us his insights about the latest on long COVID. This is the second part of our series on
this topic.

Dr. Koralnik (00:45)
We saw a lot of patient in televisit from all over the us. and sometime patient told us, well, they may be
neurologist in my area in California, Florida, let's say, but nobody is either interested or willing to take care of
me. And so that's why I'm coming to, you know, Chicago in televisit.

Margaret (01:03)
This is Conversations on Healthcare.

Mark (01:16)
Dr. Koralnik, welcome to Conversations on Healthcare.

Dr. Koralnik (01:20)
Thank you very much for having me. It's a pleasure to be here.

Mark (01:23)
You know, we understand there are roughly 17 million adults in the US with long COVID, and there are
estimates it carries enormous health in economic burdens for patients. I wonder if you could tell our listeners
about your center and its mission.

Dr. Koralnik (01:38)
Certainly. So I'm a neuro HIV specialist by training. and then I expanded my interest to all neuro infectious
disease. So in December 29 2019, when the pandemic started here in the us I was well placed to try to
understand what was going on with this new disease. And actually we started seeing a lot of patients being
hospitalized with a horrible pneumonia and a brain alteration, including encephalopathy. We thought that we
should open my clinic, my neuro infectious disease clinic for those patients when they would be discharged
from the hospital. But in fact, the majority of the people that we saw coming to the clinic were people who were
not hospitalized with pneumonia. Had a very mild case of COVID-19 sore throat cough that went away, but then
developed those lingering and debilitating complication, including brain fog, fat, fatigue, headache, dizziness,
and so on. And so to date, we have seen more than 3000 patients in the clinic with neurologic manifestation of
COVID-19. and over the past five years in the clinic opening May, 2020 for those patients, in September, 2020,
Northwestern Medicine opened a comprehensive COVID center that counted 12 specialties at the time,
including pulmonology, cardiology, gastroenterology, and so on. We added two other specialty recently,
gynecology and ophthalmology. Now, we have 14 specialty clinic for the total care of long COVID patients. So
when patients come to the center, they don't need a physician referral. They can just call, get an appointment.
They are triaged by a nurse to the different clinic that they need to see. So if they say they have brain fog and
palpitations and shortness of breath, they will come to neurology, pulmonology, and cardiology in parallel,
right? And so they see those different specialists. And in each clinic we establish, we see patients for one hour
for new appointment, we establish a differential diagnosis followed by investigation to rule out other disease.
And e every patient has a, a specialized plan of treatment.

Margaret (04:04)
Well, that, that is really quite remarkable. And I've learned some things just from your opening comment there.
And I think the, the biggest one is then there is no one specific treatment for COVID. You've got 14 different
specialty centers operating under one roof, and congratulations on getting that all up by May of 2020 when most
of the world was still trying to figure out what was going on. But given that it's very complex, very complicated,
it would seem to effectively treat patients with COVID. How, how does your center coordinate the care of

people so that people are not being treated by organ system, but treated with a comprehensive set of problems
that they bring to you?

Dr. Koralnik (04:45)
So that's a very excellent question. And long COVID is a multi system, um syndrome that may affect any organ
system actually, and some in combination brain, heart, lung, gi, and endocrinology and so on. And so this is
because the, all, all this started during the lockdown, right? So we didn't have the time and the possibility to
build a brick and mortar, you know, new building on the Northwestern campus downtown. So it was a virtual
center that um started from everybody's existing clinic. at the beginning we saw a lot of patient in Televisit,
right? So ISO provision televisit from 44 states in the US when we didn't, did not need to be licensed in every
state to see patients. And so we formed this comprehensive COVID center where we coordinated the care
through this triage system at the beginning. And then patients could be referred from one specialty to the other.
We had weekly and or monthly team meeting to try to coordinate the, the, the care of those patients, also try to
understand what we were seeing in neurology and what were they were seeing in pulmonology and in GI and
the chronology, dermatology and so on, to try to make sense of this new syndrome, right? That that nobody had
seen before. And I became the co-direct co-director of the Comprehensive COVID Center to the, together with
the pulmonologist, Dr. Mark Sala who is seeing patients himself in the pulmonology clinic. And we try to
coordinate or care the best we can and, and try to understand the advances that are, um happening in every
specialty. we also have a, a long COVID support group now for our patients who come to the Comprehensive
COVID Center. It's meet, it meets on Zoom every month on a fixed schedule. There's always a specialist of the
comprehensive COVID center that comes to talk to the patients for 15 minutes about their area of expertise. And
then a licensed social worker is there to lead the group after that provide emotional support for the patients,
patients can meet each other, understand more about what's going on in you know, other specialties and in other
patients and, and move forward. with that.

Mark (07:20)
You know, Margaret, we've had the opportunity to talk to a number of long COVID specialists at Yale and
NYU. And I'm, I guess I shouldn't be surprised by anything that we've heard about long COVID, but one of the
more surprising findings is that there are patients who've never tested positive for COVID, but now find
themselves with long COVID. I'm wondering if you can shine a light on that for some of our listeners out there,
doctor.

Dr. Koralnik (07:43)
Certainly. And that was a big problem at the beginning. You remember, during the lockdown especially, you
could not get a test if you are not seriously sick with pneumonia in the hospital, intubated, you know, because of
COVID pneumonia. And a lot of our patients at the beginning, actually half of the patient during the first six
months probably of the clinic were in this predicament. They had symptoms consistent with COVID-19, but
they, you know, they could stay at home. They did not have to be hospitalized, and therefore they were not
tested on time or tests were not available in their geographic area. And they ended up having, you know, survive
a mild case of COVID-19, but then develop those debilitating long COVID symptoms. Yet they were rejected
by, you know, medical professionals and other centers because they didn't have a diagnostic diagnosis of SARS-
CoV-2 infection in the first place. So, because we understood those limitations, and we wanted to be, as, you
know, inclusive as possible, we deliberately decided not to require a positive SARS-CoV-2 test, either, you
know PCR home test or a serological test for patient to be evaluated in the clinic. And so we saw a number of
patients at the beginning who had exactly the same long COVID symptoms, yet they were not diagnosed
formally with the COVID-19 at the time. And we decided we just to treat them just the same with supportive
measures different child diagnosis, ruling out other other condition. And we've done this ever since in every
clinic of this, the comprehensive COVID Center at Northwestern.

Margaret (09:32)
Well, it's so important to be having this conversation now when I think, you know, people have turned away
somewhat from COVID, but for the people with long COVID, of course, there's no turning away, right? Until
you improve you're in Chicago. Sounds like you were a center of all of this going on during the COVID
pandemic, I assume, at medical centers and healthcare facilities around the country. Now, there's some common
approaches to treating long COVID. But as you talk about, again, the multiplicity of organ systems involved in
the different clinical presentations, have we gotten to a place where we have common agreement on treatment
protocols, even if it's for different manifestations of the same disease, or are we still figuring it out?

Dr. Koralnik (10:21)
So I wish it was as you said, that now we have common protocols and you know, treatment that we know work
for patients. Unfortunately, it's not the case. You know, we had the long COVID Awareness Day, the first long
COVID Awareness Day on March 30 March 15th, 2025 marking the first five years of the pandemic obviously
different geographic area were struck differently by the first wave of COVID to 19. Obviously in New York, it
was worse than every anywhere else in the country. It came to Chicago a little bit after that they are different
centers that were created out of shared need, you know, to take care of those patients. and at some point, I
counted about 60 around the country for a publication that we put together. But unfortunately, I've heard that
many have actually started to close down for the reason that you mentioned that people now have moved,
moved on from the height of the pandemic. Nobody is dying anymore from COVID-19 pneumonia. We are not
talking about, you know, how many respiratory we can get, you know, for those patient, and that's great. But
COVID long COVID patient are still there. we see patient in the clinic who had, let's say, seven episode of
COVID-19, and then they picked up non COVID after the third one. There's data being published already out of
Canada and other countries that the more episode of COVID-19 people have the higher the risk for them to
develop long COVID. And so since vaccination boosters are not preventing new infections, then I think that the
number of patients is con is going to continue to increase. Uh epidemiologists have estimated that worldwide
there is more than 400 million people who have long COVID costing the economy, about a trillion dollars per
year, about 1% of the global economy. So it is really significant problem. We, since I'm a global neurologist, we
have started collaboration in Nigeria, in Colombia, and in India started neuro COVID program there as well and
published on those patient populations. So long COVID is not an American invention. It, it exists everywhere in
know in the world. here we started to be deluged with patients, and then we did the research to try to figure out
in those other countries you have to do the research first to show that the disease is there and to try to justify that
those patient need to have clinical care as well. So, going back to your initial question about protocol and
understanding I think that the, the more people publish about their experience, the better. You know other
people get informed about their you know, the the options that we have to take care of the those patient. There is
no uniform protocol, you know, for treating those manifestations. we have published what we've been doing in
2022 here at Northwestern for the Nordic manifestation, both in patients and outpatients. Other have published
also on their experience in other centers. there are uh clinical trials that have been ongoing for the treatment of
long COVID, let's say, with Paxlovid, this antiviral medication. there are two trials that have been independently
done in other places in the US, and showed no benefit from Paxlovid in a smaller sample. There's a, a trial from
the recover initiative sponsored by NIH that is close to enrollment now, and it's being analyzed. but
unfortunately there is still no diagnostic tests for long COVID and no specific treatment for the root cause of
long COVID.

Mark (14:32)
Well, Margaret, I think that's what our listeners probably wanted to ask, is what, what, what have we seen out
there anything that's promising on the horizon as you sort of look at research across the globe? It sounded like
Paxlovid might work, some cases might not. We also heard that in this first six or eight months for a subset of
the population, the symptoms diminish. but I think that's not true for everyone who has it. But what, what do
you think is promising out there? What line of research are you keeping an eye on?

Dr. Koralnik (15:06)
Alright, so excellent question. Different, um etiologies have been entertained for the root cause of long COVID,
and they're not mutually exclusive. They may, you know, be together at the same time. So viral persistence is
one, the virus remains hidden or dormant in some places in the body and needs to be treated with antiviral
medication. The treatment of Paxlovid, at least in these two smaller studies for 14 to 20 days I was not efficient.
We will await for the result of this larger study that is now we, we enrolled patient at Northwestern in many
sites in the country, and we will wait for the result of this study. That's one thing. Another is autoimmunity. The
virus comes and confuse the immune system, that there's something abnormal, abnormal in the body that needs
to be attacked. We see that in our clinic and in every post COVID clinic, actually, there is a a predominance of
women. So two third of the patients are women, and we know that women are more likely than men to develop
other autoimmune disease like multiple sclerosis, rheumatic arthritis, lupus, and so on. And we see also an
enrichment in the patient population of people who had prior autoimmune disease before COVID-19. So there
probably is an autoimmune predisposition. we are working on this in my lab, although labs are also looking at
this so far there is no medication or immunomodulatory medication that has come out of this research, which is
still ongoing. Third possibility is that long COVID is caused by a microvascular disease. And you know, that the
spike protein of the virus can bind the ACE two receptor on the surface of endothelial cells, for example, lining
the blood vessel and can trigger some inflammation or even infection of these cells. And we are have published
recently a study looking at the microvascular, um a structure of the retina in the back of the eye using a
ophthalmological technique called optical coherence tomography angiography with, um lead ophthalmologists

here at Northwestern, Dr. Manchu Gil. and we have seen a decrease in the caliber of very small vessel in the
retina in patients with neurologic complication of COVID-19. And so it is possible that this decreased perfusion
that we see in the eye is actually a window on the brain and other organs and could, could cause some of the
symptomatology that the patients have. And so that may be treatable with different, different modalities, but we
need to follow those patients over time to see if it's actually a, a real physical biomarker of long COVID. And
this is what we're doing currently in, in, in my lab.

Margaret (18:19)
Wow. Well, fascinating work going on. Dr. Koralnik and I, at risk of getting the acronym wrong, I'm going to
ask you about a session I sat in on at the National Academy of Science Engineering and Medicine a few weeks
ago, participated virtually it was focused on Lyme disease and long-term Lyme. But they talked about what they
called infection associated chronic illness. I think IACI, am I correct on that? That that's the, the acronym?

Dr. Koralnik (18:47)
Yes. It's an, it's an acronym. Yes.

Margaret (18:49)
It's an acronym that's being used. And I, I thought of long COVID in this sense, and the struggle that people
have and the struggle that entire populations have in this instance of trying to prove a disability or a limitation in
their energy, their ability to work, their ability to function without the usual markers of positive tests or positive
treatment protocols. What's your sense of where we are as a country? You, you talked about an enormous
number of people that are sufferers of long COVID. how well do you think the country has responded in terms
of support for people recognizing it as a disability making sure that we can take care of people, provide the
emotional support if we don't have treatments, treatments where we can, you're, you're in the bird's eye view of
this. What are you seeing?

Margaret (19:37)
Well, it was unexpected occurrence, obviously in 2019 and early 2020 to see all those patients coming down
with this new syndrome affecting them so much in their quality of life, cognitive function, ability to work. it was
during the lockdown, so there was not a lot of possibilities to move around. we saw a lot of patient in televisit
from all over the us. and sometime patient told us, well, they may be neurologist in my area in California,
Florida, let's say, but nobody is either interested or willing to take care of me. And so that's why I'm coming to,
you know, Chicago in televisit. so I think that people responded as best they could in their, you know, area in
their geographic area. Um the, the, the, the fact of the matter is that the, the entire world was consumed with
COVID-19 at some point with a, a, a lot of death from pneumonia. Now that that phase fortunately is over
people tend to move on, as you said, and then maybe not pay as much attention as they should to the plight of
long COVID patients. Even we have patients coming to see us. They only have probably the smell and taste,
right? They're, you know, cognition is fine. They're not fatigued, they can run the marathon, yet their quality of
life is severely affected because everything that they smell smells like rancid fish, right? and so unfortunately
there's no specific treatment for that in time. Patients tend to improve to some extent. And so the question about
disability is always a tough one because we know that some patient will improve in weeks and months and be
back to normal after that. But there are some patients who still suffer from the same cognitive problem despite
cognitive rehabilitation that we, we give them actually around ability Lab across the street from Northwestern
despite other, you know, stimulant medication that they may take, they still suffer from fatigue. And so it is not
clear yet if those patients will have this chronic condition that will la will last four years or decades, or if they
are going to, you know, get better at some point. We have developed an app actually that, um has been adapted
by Northwestern medicine IT department to be integrated into the patient's interface called MyChart for our
patients to be able to log in their daily symptom, brain fog, yes, no fatigue, yes, no, and also what their percent
recovered subjective impression of recovery compared to pre COVID baseline in percent every day, so that we
can track their, and, and they can also track their own road to recovery, um on long COVID. And these patients
are enrolled in the study. we also measured their blood biomarkers. we measured their capillary micro vessels by
optical coherence tomography angiography. and so hopefully by doing this longitudinal fund story study,
hopefully will be funded by NIH we will be able to have a better sense of what is the, what, how long is the road
to recovery from non COVID and what distinguished people who are the improvers compared to those who are
actually stable or even worsen over time.

Mark (23:17)
Margaret, we're not surprised it's a long road. We had Dr. Fauci on four or five times during the pandemic. We
had him on January, 2020. And the one thing he reminded us that Coronavirus mutates right all the time. It's
very hard to sort of nail down and it will continue to be a problem.

Dr. Koralnik (23:32)
There's a National Center for Health Statistics together with the US Census Bureau that has carried out a
household pulse study on long COVID over the past couple of years. The last data point was in September,
2024, and you had data from every state, every age group, every sexual orientation, you know, a lot of other
information about the patients who the, the people who took this study and the estimates. it's always obviously
an estimate, but that 17.9% of all US adult ever had long COVID. And if you take a population of adult, about
260 million people in the us, so it's about 47 million people, 5.3% of all adults currently suffered from long
COVID at the time of the last time point. So it's about 13 million people. And of those 80% has any activity
limitation of long COVID. So it's about 11 million people. So it's like the population of New York plus Chicago
put together. so I think this is the best data that we have from the national center for Health statistic in the US
Census Bureau. Certainly very serious outlets, you know for, for measuring the number of people who have a
typical disease in the, in the country. If you would just google long COVID household pulse study It's housed on
the CDC website. You can click on the link, go on the table and see all the data for yourself. I think that's a, a, a
very interesting exercise.

Margaret (25:22)
I know our time is running a little bit short, but I have to ask you certainly we've seen some research that found
no significant, significant differences in long COVID symptom severity between patients who were vaccinated
or not vaccinated or vaccinated after a preceding course of COVID infection. Is that accurate to say? Is that
what your research bears out? Did being vaccinated make a difference in whether or not you developed long
COVID if you did get infected?

Dr. Koralnik (25:55)
So the question is, does vaccine do vaccine alter you know, the presentation of long COVID? And at the
beginning of the pandemic there, there were a lot of urban legends. That vaccine either cured long COVID or
vaccine made long COVID worse. we looked at this in our patient population at the beginning, and we didn't see
any effect. And more recently, we published a paper on, in brain communications on 1300 patients seen in the
clinic the first 1300 patients in, in the clinic including 200 who had previously been hospitalized for pneumonia
and 1100 who were never hospitalized. And we looked at patient who got COVID, got vaccinated, and then
developed long COVID compared to those who got vaccinated, got COVID after that, and then developed long
COVID. And those two population were almost identical. Right. So in, in the, in this study based on my clinic
population and we did not see any effect of the vaccine on the subsequent development of long COVID some
data comes from large epidemiological studies for, for example, from the VA hospitals and others, where they
saw that patients who got vaccinated had a decrease incidence of long COVID after the fact. but a, a mild
decrease, maybe 15 to 30% at best. but when we see them coming in the clinic, whether they had COVID before
or after the vaccination, if they developed long COVID, it's really the same disease

Mark (27:41)
You know at our health system here, what we focus in on the under-served and uninsured throughout the
country. And one of the programs that we're very excited about and really aligns with something that you're
doing is to provide e consults to providing access to primary care providers through a specialist. and we've done
a couple hundred thousand of these, and high on that list is neurology. And I know you've been focusing on
neurology residents in Zambia because you're thinking more globally and which is a real shortfall, obviously
neurology for so many population groups. I'm wondering if you could share with the audience what insights
about the current international health situation that they're facing with all the budget cuts that are happening in
Washington.

Dr. Koralnik (28:33)
Alright, so it is a very large question to answer, but since you're talking about Zambia I've been fortunate to help
a young than neurology resident called Dr. Omar Siddiqi, when I was still at Beth Israel Deaconess Medical
Center in Boston, to establish himself actually as the second neurologist in Zambia, a country just about the size
of Texas. It happened about 2010. He trained at Harvard in neurology, was interested in global health, global
neurology. We had the connection with the one neurologist who was in Zambia. And by getting a one year grant
and another one year grant, and then a five year grant from NIH was able to establish himself full time. from
there in Zambia from there are other people have joined, including Dr. Deanna Sailor from Johns Hopkins, and
others who have expanded this program. Finally formed the first neurology residency program in Zambia in
2018. and then the first graduates became attending that in that program. And one of the proudest moment of my
career was one year ago at the American Academia of Neurology, when I saw the first graduate of this program
chairing a session of global, nor in global neurology in the American academia of um neurology. so Dr. Macina
Tromba actually is is this brilliant young neurologist. So this, this started, you know, from the, the one person

effort really. And then other people came and created the, the critical mass, you know, for that to continue. And
now the Zambians are training Zambians to become neurologists which is obviously very good for them. we
have been sending trainees, residents and fellows you know, almost every year for a rotation in resource limited
setting and heavy infectious neuro infectious disease setting also for their own training. And when they come
back oftentimes they say that it was really a life altering experience to, to be able to, to you know, to, to go there
and, and see and, and learn from, from the, the people who are seeing those patients. Now, obviously there is a
lot of limitations based on NIH funding. the, the program initially was not created through NIH. it was created
through other foundations, but obviously all the, the, the, the salaries of the people who are on the ground need
to be supported one way or another. And so, NIH was a big, big part of that. I truly hope that, um we will be
able to continue to do that. I currently collaborate in Nigeria, in Colombia, Latin America, and in India. I think
we can definitely learn from them as much as they can learn from us. and infectious disease are, you know, don't
know any borders. they don't know any ideology or political, political orientation. Everybody's fair game. And
so if we understand that we are really all in it together, then we need to continue to, to work together to fend off
those infectious disease that can affect us in the US just the same as in Africa or in Asia, Latin America.

Mark (32:19)
That's a great Message

Margaret (32:21)
A great note to end on. Congratulations for that accomplishment. I'm sure that was a very high moment, not the
last high moment, a very high moment in your career. So thank you, Dr. Koralnik, for joining us. Thank you to
our audience for being here. And just a reminder to be sure to subscribe to our videos on YouTube, find us on
Facebook and x, and please share your thoughts and your comments about this program. Take care, and be well.

(32:48)
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