“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.”