[Avindra Nath] We did anticipate that there would be
neurological complications right from the very beginning.
I've been studying viruses since the 80s when the AIDS pandemic started,
and it was the same story there too.
A lot of people have long term cognitive problems,
even if the virus is well under control.
What affects the brain can be extremely devastating,
because it can affect your personality,
your ability to think and concentrate, your mood.
Those things that make us a person as a whole.
[Narration] When SARS-CoV-2 emerged, many were
initially focused on its impact to the lungs.
It soon became apparent that COVID
takes a toll on the entire body–
from the gastrointestinal tract to the brain.
Autopsies have revealed devastating damage in the brains of those who have died from COVID.
[Avindra Nath] The blood vessels were damaged,
there were inflammatory cells around the brain.
We found that there were immune cells in the brain itself.
And we found antibodies stuck to the blood vessels.
We knew that they were attacking the blood vessels.
I had expected that we will see a lot of virus in the brain
because the virus affects the nose.
To our surprise, we didn't find the virus in the brain.
Now there are a few people that have reported
detection of virus in the brain,
but they find very, very small amounts
and it doesn't explain the pathology that you see.
[Narration] Most of these autopsies were conducted
on individuals who had severe cases of COVID.
Less is known about brain damage in those with long COVID—
symptoms that persist for weeks after what is
often a relatively mild stage of acute infection.
Studies estimate that up to 30% of people develop long COVID
after an initial SARS-CoV-2 infection,
and that women are at greater risk than men.
The symptoms can include fast heart rate,
shortness of breath, and various neurological issues.
[Serena Spudich] We've actually seen over time,
now that we have seen hundreds of patients,
and lots of people have been reported in literature too,
there are these kind of major categories.
One of them is what people call brain fog,
where really, your brain is just not functioning properly
for some sort of cognitive types of tasks,
things like concentration, memory.
People have skin changes, where they basically say,
"Wow, the sensation on the surface of my skin is really abnormal."
And then another major category that we've seen is headache.
There is the sort of psychiatric categories, where people have
rarely had a much more acute and profound
sort of delusion or psychosis syndrome.
I think it's been a real challenge for patients
that they come into their doctor with symptoms,
and the tests that are run are negative.
And even things like MRI, which is a very sensitive test
that can find lots of changes in the brain,
for many of these patients is normal.
For a long time we've been using research tools
that can look at more sensitive measures,
that aren't things that we necessarily use in the clinic,
but can tell us things like whether the immune system is
functioning completely normally, or whether there might
be very subtle injury to the neurons in the brain
that you just can't see by looking at an MRI scan.
[Akiko Iwasaki] There are three hypotheses that can potentially explain
how long COVID can affect the brain.
One is a direct infection of the virus
of some cells in the nervous system,
or supportive structures in the brain.
Second hypothesis is that there are auto immune responses
that are attacking parts of the brain.
That could obviously trigger lots of different symptoms,
and long duration of such responses,
because once the autoimmune cells are activated,
it's very hard to deactivate them.
The third possibility is that there is distal inflammation happening,
such as in the lung, that could stimulate cells within the brain,
and trigger long term changes in those cells.
So a combination of these could be happening,
or it could be a sequential event of things that happen,
and they all contribute to these neurologic issues.
[Narration] Long COVID clinics across the world are trying different
rehabilitation approaches to improve these symptoms.
[David Putrino] Our nervous system has a whole portion of it
that is dedicated toward doing all of the things your body
needs to autonomously control.
When that gets knocked out of balance,
that's called dysautonomia.
Dysautonomia has also been reported in other cases of post viral illness.
Autonomic rehabilitation is a very personalized, and a very delicate approach
to rehabilitating the autonomic nervous system.
For most people that we see with long COVID,
it typically begins with very, very gentle movements,
paired with breathwork with a patient laying flat on their back,
slowly performing movements that increase blood flow into the chest cavity.
It's not exercise, it's not aerobic–it’s very gentle.
We've had good response to cognitive symptoms from autonomic rehabilitation.
I think it's worth mentioning that not all cognitive symptoms
are from dysautonomia.
And so in some cases, we don't move the cognitive symptoms at all.
[Narration] Researchers are also beginning to conceive of drug treatments
that may address the underlying causes of long COVID.
A team at the National Institutes of Health is awaiting
regulatory approval for immune modulating drug trial.
[Avindra Nath] The plan is to bring in patients, we're going to keep them in
the hospital for a week.
One arm will get placebo, the other arm will get intravenous immunoglobulin,
and the third arm will get intravenous corticosteroids.
They're Sledgehammer approaches.
They're not very precise attacks, right?
They affect the immune system in many different ways.
[Akiko Iwasaki] Vaccination in long COVID patients
have an impact on their symptoms.
Some people feel much better from vaccination.
That could eliminate the source of these persistent virus or viral remnants,
or, you know, something that's basically persisting in these patients
That's triggering the chronic inflammation.
Number two, some people don't feel any difference at all.
But there are some people who feel worse from vaccination.
If a person is suffering from autoimmune disease for example,
the vaccine-induced inflammation might exacerbate the autoreactive lymphocytes,
and therefore make the disease temporarily worse.
The ultimate goal is to try to understand what we can do
to help them feel better without using the vaccine,
because vaccine doesn't work on everybody.
But if we can figure out what triggers
the better improvement in their symptoms,
then we can try to emulate that with other therapies.
[Narration] Many hope that knowledge gained from long COVID reserach
will benefit others grappling with post-viral illnesses.
[Avindra Nath] We have millions of people suffering from not only this,
but very similarly related diseases–
post-Lyme syndrome, Gulf War Syndrome, ME/CFS.
Patients, they're going from physician to physician,
nobody knows what's wrong with them.
People tell them, "well, it's all psychological" or anything.
But they have real disease.
Now we have a superb opportunity to put the best tools that we have available.
to us, to try and sort this out.
If we could do that it will have a huge impact in the field.