Liza Fisher: “I got sick and I just never got better.
It hit every system in my body, the internal tremors and vibrations. This is me now.”
Akiko Iwasaki (professor of immunobiology, Yale School of Medicine): “I get emails
and messages from people who are suffering from long Covid every day. Some of these stories are
very emotional and devastating.”
Tillie Adams (11 years old): “Feeling sick all the time, belly aches all the time,
leg aches. And then I get headaches, like pains in my eyes. I don’t feel like myself anymore.”
Tanaeya Taylor: “I can’t work. I can’t drive. When I do drive, I feel like I am driving drunk.”
Dianne Sheehan: “Exhaustion to the point where you can’t remember your kids’ names.”
Woman with Covid-triggered postural orthostatic tachycardia syndrome (POTS): “I am
formerly an ICU nurse and have not been able to do that in almost a year.
I have horrible vertigo. The mental fog is like nothing I’ve ever experienced before.”
Colin Bennett: “It’s absolutely the worst hell you could ever imagine.”
Akiko Iwasaki: “Their lives have been ruined by long Covid and they’re no longer able to
go back to work or work at the old pace that they were used to doing. These stories are
accumulating within me and drive me really to do more research and
to try to find something that we can do to help the suffering of these people.
“There is urgency to understanding this disease because there are people suffering so much so
that they are contemplating of taking their own lives to end the misery. If we can stop
one more person from such an act of desperation, I think we would have done our job. So, every day,
every minute counts. And I understand that, and that’s part of the reason I don’t get much sleep.
“When Covid hit in early 2020, my lab was ready to tackle some of the key questions, such as
how does the immune system respond to the virus infection and what causes severe disease
versus mild disease? But during the course of investigation, we’ve also been encountering a
lot of people telling us about their lingering symptoms that last for very extended time period,
some of which are debilitating.”
Pamela Bishop: “The symptoms that I have every day are fatigue, nausea, dizziness,
headache and some sort of pain. I have a lot of GI issues. I’m very nauseated
most of the time. It’s hard for me to eat a full meal without getting sick.”
Beth Ann Pardo: “I have joint pain, muscle pain, fatigue, tremors,
brain fog, severe anxiety. I’m not even the same person I was
before. It’s completely ruined my life. It’s completely changed my life.”
Akiko Iwasaki: “Through the conversation with the patients and the doctors who are
treating these patients, we became quite aware of this phenomenon of long Covid.
“We didn’t anticipate so many people becoming ill with long-term consequences.
Hospitalized patients who are discharged may have 50 percent of those having long-term
symptoms. Whereas a mild Covid or asymptomatic ones may lead to much less prevalence but still
in the 10 percent, 20 percent, 30 percent range. So that’s a lot of people.
“Vaccination and prior infection will likely reduce the chances of you getting
severe Covid and even potentially long Covid, but it’s not a guarantee.
Some people get long Covid after being boosted and gotten a breakthrough infection.
“Even if the pandemic virus spread were to stop today, we still have tens of millions of people
suffering long Covid and that’s a parallel pandemic that’s happening,
which is getting a lot less attention than the acute and severe Covid, even though the cost
to lives and the quality of lives that these people have to live with are very limited.”
Akiko Iwasaki: “Long Covid can impact any part of the body.
It’s really not a respiratory-only disease, at all. It basically involves every organ system
that one can imagine, starting with the central nervous system, the peripheral nervous system,
the GI tract, the respiratory, cardiac, musculoskeletal system, just basically everything.
Depending on the person, it may be a set of organs that are involved or just one. There’s
a huge heterogeneity, but I don’t think any organ is spared from the impact of long Covid.”
Andrea Tomasek:
“100.1. Yesterday was my 20-month anniversary of having a fever. So I’ve had a fever for 20
months and one day. Doctors don’t know why I have a fever. I’ve been to the Mayo Clinic
and their solution was to not think illness thoughts. Mm-hmm.”
Samir: “You may have heard that long Covid is a mental illness.
I can guarantee you it is very physical as well. One of my symptoms is muscle spasms,
where randomly some of my muscles will contract, leaving me in pain. Because of that,
I’m trapped in this wheelchair, this bed, and this room. Long Covid isn’t just
mental, it’s physical as well, and I spend most of my time in total physical pain.”
Akiko Iwasaki: “We are seeing clear biological differences in the measurements that we’re
making in long Covid patients compared to people who had Covid, who fully recovered from Covid.
We need to kind of move beyond this notion of psychosomatic origin of disease and really look
into the biological origin, biological reasons why these people are suffering.”
Akiko Iwasaki: “There are over 200 symptoms reported
for long Covid. Some people have one or two of these while others have over
a dozen symptoms ongoing at any given time. Not everyone has the same disease,
and I think that speaks to different endotypes of long Covid that people are suffering from.”
Sen. Tim Kaine: “I would say I’m experiencing long Covid. There are people who are really suffering
it. I wouldn’t call myself a sufferer. I have a bizarre nerve-tingling sensation that feels like
my skin is dipped in an Alka-Seltzer that’s just going off 24/7.”
Akiko Iwasaki: “But the range is anywhere from people having
some pain or shortness of breath and fatigue.”
Joel Fram: “The fatigue was really bad, and I would also get breathless doing very
normal things like walking up the stairs. It was really scary.”
Akiko Iwasaki: “All the way to people having internal tremors and vibration who are just
unable to do anything else because their body is just moving in a way that they cannot control.
They cannot sleep, they cannot eat, they cannot think, they cannot do anything. And they’re just
under such a great physical and mental strain from such symptoms that these are the people,
unfortunately, who have taken their own lives or who are contemplating ending their lives. Those
are extreme symptoms, but there is a huge range of symptoms. And ultimately we need biomarkers
to say, OK, you have this kind of Covid or that kind of Covid and we’re not there yet.”
Akiko Iwasaki:
“I believe that the ME/CFS [myalgic encephalomyelitis/chronic fatigue syndrome] is
probably of the same disease that people with long Covid are suffering from but
were caused by other infections.
“Prior to long Covid, there have been a number of infections, many, many viruses, but sometimes
bacteria and parasitic infection that leads to long-term consequences. It’s only with the
sheer number of people with long Covid that really now is highlighting these other diseases such as
ME/CFS that’s being triggered by numerous other pathogens. But the symptoms are
very similar to long Covid such as chronic fatigue as well as some of these dysautonomia-like
syndromes, cardiac issues, GI issues, many vasculature issues, and just inability to control
these heart rates or blood pressure or things that are very similar to what we’re seeing with long
Covid. It’s a wake-up call really for the society to start looking into other post-acute infection
syndromes, because we are going to be dealing with this going forward. Some of these long Covid
patients might develop into ME/CFS if they cannot recover from the long Covid stage of the disease.”
What causes long Covid? Akiko Iwasaki: “Long Covid disease
pathogenesis can be considered as having four separate causes
but these are not mutually exclusive. People can have a combination of these things too.
“So the first hypothesis is that there are maybe persistent virus hiding somewhere
in the tissue which you cannot measure with the nasopharyngeal swabs or saliva because
these people are PCR-negative. But imagine having that in your gut or some other organ,
and that type of persistent virus, or it could be just the remnant of the virus, such as the
protein or the RNA or combination thereof, that could be triggering the chronic inflammation.
“Second hypothesis is autoimmunity. Autoimmunity can be triggered as a result of an acute infection
and once these autoimmune cells, which are T cells and B cells that
are reactive against our own body, our own host proteins or molecules,
it’s very difficult to shut them down once they are triggered,
because the stimulus that are triggering them is everywhere. Essentially, it’s your own cells.
“The third possibility is dysbiosis of microbiome. So we have trillions
of bacteria in the gut and they really contribute to our health
but potentially disease if they’re disturbed in their compositions or their metabolic functions.
And it’s also possible that there are latent viruses that are reactivated to cause some
of these symptoms such as the Epstein-Barr virus. So that’s the third hypothesis: It’s really about
whatever that’s in our body that’s sort of dysregulated, either microbe or virus.
“The fourth possibility is tissue damage that’s incurred
by the initial infection that cannot be repaired. And this is likely happening in the
hospitalized patients who were intubated or had some extreme measures of medical interventions.
If you have severe respiratory infection with SARS-CoV-2, you obviously have damage in the lung.
If you’ve had pneumonia, there’s scarring and potentially fibrosis.
Those types of tissue damage is very difficult to repair. If you look at the UK Biobank study,
there is significant reduction in brain mass of people even with milder Covid.
So that’s a direct damage to the brain after even a milder infection, and there may be
other damages that we don’t know about, vascular damage. There may be a lot of clotting issues or
issues related to the endothelial cells that may have incurred some damage. And of course,
endothelial cells are very important for the function of the blood vessels as well as
oxygen exchange and so on. So I think there may be many damages at the microscopic level, like
the vasculature, or more the macroscopic level, like the brain itself or the lungs. And there
may be damages in the liver or intestine or other tissues that we don’t currently appreciate with
respect to what’s happening. So these is roughly the four major hypotheses but there may be more.”
Akiko Iwasaki: “With respect to treatment, if the first hypothesis of
persistent virus is leading to long Covid is true, then we need to go after the virus
as treatment. One thing we can do is to use antivirals like Paxlovid or Molnupiravir
that targets the virus itself and we can maybe eliminate the source of the problem that way.
It’s also possible that some people feel much better after vaccination and that might be
because there was a persistent virus reservoir that was cleared by vaccine-induced immunity.
The therapy for that group of long Covid patients would be antiviral measures.
“If long Covid is causing autoimmune disease,
first of all the target of autoimmune disease needs to be identified. What are the T and B cells
attacking in such cases? Because that will inform us how the host immune response is harming
the host. If we know that these patients are suffering from some sort of autoimmune disease,
there are interventions that are already existing in the autoimmune disease treatment such as
immunosuppressives or even biologics to eliminate B cells that are the source of autoantibodies.
And there are newly developing biological drugs that can be applied to long Covid.
“If Covid is somehow inducing dysbiosis — which means that some harmful bacteria may be
expanding in lieu of the better, sort of more commensal bacteria in their gut — we may be
able to go after either the metabolites that the bacteria is producing that’s harming the host. We
can try to block that pathway or just trying to change the composition of the microbiome
through diet or probiotics or some other mechanisms.”
Akiko Iwasaki:
“For someone who’s newly infected, I would definitely recommend to get the Paxlovid
right away, because the earlier the treatment the more likelihood of you being able to eliminate the
source of viral reservoir. And actually treating early with Paxlovid or monoclonal antibodies is
just in general great to avoid any of these four hypotheses of diseases from occurring, because
the longer you allow the virus to replicate and cause damage, the more likelihood of you
triggering these four types of disease outcomes. And there is even a study that suggests that
getting vaccination within the first 12 weeks of infection reduces risk for developing long Covid.”
Alyssa Milano: “After my second vaccine, my long-haul symptoms started to ease up,
which I guess happens to like 40 percent of long-haul patients. But I still have
shortness of breath sometimes and heart palpitations and tingling in my hands
and it’ll come out of nowhere. And it’s scary when it happens.”
Akiko Iwasaki: “So even vaccination may be helpful during the early phase of infection,
but if you wait too long these things aren’t going to be effective.”
Akiko Iwasaki:
“I’m personally surprised that long Covid isn’t at the center of discussion in public.
Knowing how devastating this disease is, I am very hesitant myself to go out there and get exposed to
any kind of Covid. I just think it’s really gambling with your health and
it’s not safe. I personally think that removing precautionary measures to prevent transmission
is a very bad idea. I do absolutely ensure that my children are fully vaccinated,
boosted if they’re eligible, and are wearing masks inside while they’re going to school or elsewhere.
We need to layer protective measures, one on top of the other,
in order to reduce the risk of getting Covid so that we don’t get long Covid either.”
Lila Bishop (speaking to Pamela Bishop): “I feel sorry for you all the time.
I want doctors and researchers to help find a cure for it, but I don’t know if they can.”
Pamela Bishop: “I think they can.”