Michelle Monje (neuroscientist and neuro-oncologist, Stanford University):
“Inflammation in the brain can cause dysregulation of a number of different
cell types and have lasting consequences to cognitive function. Understanding that when
the pandemic struck and we saw how profoundly immunogenic, how profoundly inflammatory
even relatively mild cases of Covid could be, I really worried about a neurological health crisis.
And I think we’re watching that unfold right now. The rates of persistent cognitive symptoms
in people who have recovered from Covid is
frankly alarming. We need to understand how to intervene and offer effective therapy, or there
are going to be just millions of people suffering with these persistent cognitive symptoms.
“I’m not an epidemiologist. I’m not a virologist. I’m a neurologist.
But I am alarmed by the neurological possible consequences of this pandemic and alarmed by
the neurological disease that’s already evident in many, many, many survivors of Covid.
“Even from early in the pandemic, it was very clear to neurologists that
Covid infection results in a remarkably high rate of persistent neurological symptoms,
including quite a high rate of persistent cognitive symptoms. That includes things like
difficulty paying attention, difficulty with the speed of information processing,
difficulty with concentration and memory. And that is something that we should all be paying
a lot of attention to — that is really, really concerning, it’s debilitating. People are just not
returning to their previous level of function. And that’s a major problem with 265 million people
worldwide infected with Covid [as of January, 2022; over 526 million cases by May, 2022], and
some estimates of as many as 1 in 4 people, at least prior to the time of vaccination,
experiencing these cognitive symptoms. This is a neurological health crisis.
“I’m a neuro-oncologist and one of my clinical specialties is to take care of people following
cancer therapy who have persistent brain fog: cognitive impairment as a result of their cancer
and its therapy. And this so-called chemo brain, or chemo fog, is very similar to what people are
describing after Covid. And so this so-called Covid fog shares almost the identical symptoms.
And what we’re finding in the laboratory is that the two types of brain fog also share
a lot of the very same cellular changes that we think are underpinning this sort of fogginess.
“We know that with severe Covid infection, that many things can go wrong, that severe disease
is associated with blood clots that can cause stroke with even direct infection of the brain,
and with the consequences of multi-organ disease and damage. But even after mild Covid,
people were reporting persistent cognitive trouble. And I wondered
whether the inflammatory response just to the respiratory infection
might be enough to trigger neuroinflammation — inflammation in the brain — and consequently
dysregulate these cells that are so important to keep in balance for healthy cognitive function.
“What we discovered in the laboratory in mice that have relatively mild respiratory Covid and then
in human samples, Covid elicits such a profound inflammatory response in the brain.
And as a result of that, brain cells that need to work together
in order to communicate and function normally were dysregulated. In severe cases of Covid, there
can be direct infection of the brain, but in many cases, there’s no evidence of virus in the brain.
“What’s happening to affect the brain instead is a consequence of the immune response to the virus.
And what we studied was how the immune response
to infection that was limited to the respiratory system could cause inflammation in the brain
through signaling molecules that go from the lung, through the blood and to the brain. We found
pretty high levels of inflammatory molecules called cytokines and chemokines
in the central nervous system, just from mild respiratory infection.
“And together with that, we saw inflammation in a particular kind of brain immune cell,
which is called a microglia. When microglia and astrocytes become reactive,
they then can cause dysregulation of another kind of glial cell that form the insulation
around axons — quite literally like the insulation on a wire. When that happens,
the neurons (the communicating cells in the brain) can’t communicate with each other in their normal
way — not as quickly and not as well. And so that can cause dysregulation of the whole circuit and
cause cognitive impairment. This pathophysiology is particularly prominent in Covid.”
Michelle Monje:
“Now a lot more kids are becoming infected with Covid. And so one of the next things
we’d like to explore in the laboratory is to understand how early life exposure to even mild
respiratory Covid might influence both brain development, brain plasticity and cognition.
As a parent, as somebody who takes care of children in the clinic, after Covid
exposure I’m very attentive to how school is going, to whether they’re complaining about
not being able to remember things, if they’re having difficulty finding their words, to describe
certain things in conversations, their overall level of fatigue. I think there’s
many things to pay attention to as a parent, as a teacher, as a physician.
“It’s not clear what neurological diseases people may be at increased
risk for down the road. And so it’s of some real urgency to understand that,
to understand these neurobiological underpinnings of this initial response to Covid, to know
what people may be more susceptible to, and to reset these cells to a more normal state.
“The risk of long-term neurological disease really gives me pause and makes me not at all ready
to decrease mitigation efforts. I still feel that we need to be vigilant. We need to not fatigue of
these measures, as difficult as they are. We need to really maximize vaccination and hope
to minimize the long-term damage that this pandemic is going to do for generations.
“I think the lessons from chemo brain are really encouraging, because the biology that we uncovered
in the context of cognitive impairment are all potentially reversible. And that’s
really hopeful. In more severe cases of Covid, particularly when there are clots and strokes and
direct brain infection, irreversible damage can happen. But in these more mild, acute Covid cases,
this is all potentially recoverable. It’s of real urgency to understand the neurobiology,
to understand the basic underpinning of what is going wrong, so that we can develop therapies
to intervene and restore normal balance in the brain. Otherwise, I think that there will be
really profound long-term consequences of this pandemic on neurological health.”