Covid on the Brain, with Heidi Bender and Lish Ndhlovu

What’s causing the “Covid fog” and “long-haul Covid” that have been all over the news lately? Neuropsychologist Heidi Bender and infectious disease specialist Lish Ndhlovu explain how the virus is getting into the brain, what it does when it gets there, and how that affects cognition, emotions, and behavior.

Plus… hear firsthand from a patient who went through the fog — and came out the other side.

Phil Stieg: Hello — This week we are releasing a special expanded episode exploring several aspects of Covid 19 and its effect on the brain.  I’ve asked two of my colleagues here at Weill Cornell Medicine to help us understand what Covid does to the brain, how it gets into our nervous system, and what can we do to treat the sometimes devastating aftermath known as the “Long Haul Covid”.

First, we’ll talk to Dr. Heidi Bender, an award-winning neuropsychologist and part of our team within the Department of Neurosurgery here at Weill Cornell – New York Presbyterian Hospital.  Since joining our staff in 2020, she has been on the front lines of dealing with both the neurological damage wreaked by this disease, and the secondary psychological impacts that arise from the experience of surviving Covid 19.

Heidi, thanks for joining us today.

Heidi Bender: Thank you so much, Dr. Stieg. It’s an honor and privilege to be here with you again.

Phil Stieg: So let’s start off with what neuropsychology is.

Heidi Bender: So neuropsychology, it’s the study of brain and behavior relationships.  [It’s really] that intersection between neuroanatomy and cognition, emotion and behavior. How we think affects how we feel and how we feel can affect how we behave.

Phil Stieg: I also think that patients and the lay public frequently confuses a neuropsychologist with a psychiatrist. Are there fundamental differences in the approach towards the patient that the two subspecialties take?

Heidi Bender: I mean, never having been a psychiatrist, I could only assume, but I mean, one of the first things I do when I meet with a patient is I just let them know, look, I’m a Ph.D., not an M.D. I explain to them what a neuropsychologist is and I try to dispel any sort of myths right off the bat. I let them know that at the end of the day, our recommendations are going to be, interventional or consultative, meaning we might say consult with this one, consult with that one.  Our recommendation at the end of the day is not going to be take these three medications and call me in the morning.

Phil Stieg: There seemed to be a number of symptoms that patients are experiencing related to covid-19, such as confusion, brain fog, changes in behavior. And what do you do as a neuropsychologist to help people with the after-effects of covid-19?

Heidi Bender: So neuropsychologists are really at the forefront of this long-term battle with covid-19, because our expertise really uniquely positions us to evaluate a patient throughout their acute treatment course and also serially over time. And this serially over time part is particularly important because the preliminary studies have shown that a sizable minority of survivors of covid-19 have long term cognitive or neuropsychiatric consequences.

Phil Stieg: I really want to clarify, since we’ve only known about Covid-19 now for a little bit over a year so, that people listening to this aren’t frightened. When we say the long-term effects, we’re only talking about a year that we know of for now. So can we put that in perspective?

Heidi Bender: I think it’s really important to know that when we talk about long term recovery in terms of covid, most of the people who are covid-19 survivors do tend to recover from cognitive and neuropsychiatric consequences within a three-to-six-month window. However, we do know that a sizable minority have persistent symptoms that go beyond that frame.  A  year and change ago, we never heard of the word sars-covi-2 and covid-19. And this is the whole new language that we’re all learning about together. And although the literature has been coming out fast and furious, as the time goes on, we’re learning more and more. And sometimes the literature is actually contradicting itself. We know what we know today, but we don’t know what we’ll know tomorrow.

Phil Stieg: Can you list the kinds of symptoms that you are seeing patients for most commonly?

Heidi Bender: So attentional variability is one, two and three that’s sort of going in and out of paying attention, vigilance, difficulty paying attention for prolonged periods of periods of time and brain fog.  Those are two words that come up time and time again in this population . And it’s really, regardless of the severity of the patient’s actual covid-19 infection.  And our patients really describe this brain fog, like walking through molasses –  information and words that are usually easily accessible just feel just beyond their reach.

Phil Stieg: A question about the pace of the onset of symptoms. I don’t want people worrying that they’re fine one day and then boom, all of a sudden they’re hit with fog. Is is this more of a gradual onset? And then the importance of that is if you feel it coming on and you know, you have covid, should they seek help more quickly?

Heidi Bender: You know, it’s very hard to say because we know that the severity of infection really does in some ways predict who might have the most acute cognitive symptoms. We know that covid-19 has the potential to be neuro-invasive and can cause stroke or encephalopathy or have peripheral nervous system dysfunction or seizures.  This group is, of course, at increased risk for long term cognitive consequences and should absolutely seek acute help so we can get right in there and help the patient as they are just kind of coming out of those illnesses.  Also, in terms of patients who perhaps had more severe covid, those who required a prolonged ICU stay or mechanical ventilation, we know that these patients are at increased risk for long term cognitive effects and these folks also are the ones who should start getting care most immediately. But we know about 80 percent of covid survivors didn’t require hospitalization or who had more mild symptoms.  Those are the ones who should really be very mindful of their symptoms, be very mindful of where they were pre- covid, where they are post-covid and how much help and support they think they’ll need. And obviously, if they need help, we’re there to help them.

Phil Stieg: There is great concern among the general public about the effect Covid 19 can have on our brains and nervous system.  Yet, surprisingly little is known about how Covid gets into the brain and what effect it has on blood vessels and nerve cells.  To understand more about how this disease invades out brains, I consulted another of my colleagues, Dr. Lish Ndhlovu, professor of immunology and medicine at Weill Cornell Medicine’s Division of Infectious Disease.

Lish, thank you for being here with us today.

Lish Ndhlovu: Pleasure.  Thank you for having me.

Phil Stieg: Perhaps we could start with just a general comment. On what? Affects covid has on our central nervous system.

Lish Ndhlovu: Yeah  , since the outbreak of the, Covid-19 disease back in sort of the end of 2019, it’s been evident that there are patients who continue to, you know, have quite diverse clinical manifestations of the disease and from asymptomatic outcomes to really severe pulmonary effects.  We are now aware that this disease really does target many, many components of the body, including the brain.   I think we’re beginning to see the first signs that there is clear injury. What’s driving that injury? Is it because of the virus directly or bystander effects?  So at this point, it’s anecdotal.  We really don’t have a definitive answer.

Phil Stieg: What about the fact that people lose smell and taste? So it does appear that the virus does invade the olfactory system, which technically speaking, is part of the of the brain. But we have no evidence that from there migrates into the brain. Is that correct?

Lish Ndhlovu: The degree to which the virus enters the olfactory system, I think is, again, an area of intense investigation. And I think you’re absolutely right. This is certainly linked to the central nervous system. But at the moment, you know, the data is really unclear.  But there’s a lot of investigation in that area to try to explain that.

Phil Stieg: So let’s start with the blood vessels. Obviously, the virus is in your blood. And what does it do to the blood vessels in the brain?

Lish Ndhlovu: So I think I think similarly to what we see in the periphery, the endothelium, we do think there is endothelium damage,

Phil Stieg: Which is the cells lining the blood vessels.

Lish Ndhlovu: That is correct. This is also relevant when you think about the blood brain barrier. This could potentially be disrupted, allowing entry of the virus. That is a component that interacts with the endothelia, which is sort of lined with the the blood vessels.  So we do show very clear evidence of endothelia damage. What may be driving that could be either viral components, but also potentially, as I mentioned, this inflammatory cytokine profile, which also could impact cells in the brain as well.

Phil Stieg: So that’s what I wanted to get into. That is, once you injure the blood vessel, the blood vessels become more leaky, presumably, and then both the virus potentially could get in into the brain. But more importantly, all these, you know, inflammatory cells get into the brain and what do they do?

Lish Ndhlovu: Some of these cells are very useful. They’re out there to try to control the infection.  Neutrophils, macrophages, 4 T cells sort of an HIV. We sort of seen the immune dysregulation that happens.  And it seems to do a number of similar activities. And in fact, we’ve been looking at individuals who both have HIV and covid and those that  have HIV alone or covid alone,  and  to try to try to map out this immune dysregulation and the cytokine storm that we see. And probably they have some similarities.

Phil Stieg: Can you explain what cytokines are?

Lish Ndhlovu: Yes, it is just circulating inflammatory mediators that are produced by different cell types to try to trigger an immune response, to try to be protective against invading pathogens. And sometimes the responses can be overexuberant and those can lead to tissue damage and reactivate sort of the wrong cells. And that leads to an exacerbated response. This can be quite dramatic, very early, and infection can be quite detrimental to the individual.

Phil Stieg: It’s not one of the hallmarks of the covid infection is that there is this exuberant overreactive  inflammation within the brain?  And that’s presumably one of the reasons why we have brain injury?

Lish Ndhlovu: You know, it’s interesting. Similar to HIV, while we think of it as an immuno-suppressive disease with the   loss of T cells, Covid does the same thing. So there’s a culprit. We have this balance between an inflammatory, exuberant response to damage, but also a loss of immunosuppression, the loss of cells that are there to try to help the immune system to function. The balance between the two have really been an issue as we try to find therapeutics, because we don’t know if we’re shutting off the inflammatory response, which is driving disease, but that could also be protective.  So we really are in a conundrum. And that’s probably why many therapeutics targeting the immune system have not worked. We haven’t yet found that balance and timing.  When to impact the immune system.

Phil Stieg: A re there any signs or markers that you look for in a person’s blood or from any system that would indicate that they’re at higher risk for brain injury from their covid infection than somebody else?

Lish Ndhlovu: I think that’s actually a terrific question. And I think we can learn a lot from, you know, the neuroscience space from degenerative diseases like Alzheimer’s. I mean, we have really some remarkable investigations of potential biomarkers that impact the brain. I think we’re beginning to test some of these predictive markers. Hopefully, we’ll have predictions of who may be at risk of developing severe disease I think is first and foremost.

Phil Stieg: So I’m getting the sense that we’re basically at the tip of the iceberg in terms of, you know, what could be the impact on dementia or other chronic debilitating diseases of the brain.

Lish Ndhlovu: Very, very, very true.

Phil Stieg: Lish Ndhlovu, I’m hopeful that this information will forewarn people, but also make them feel comfortable that isn’t as bad as the news would make us believe. Thank you for being with us.

Lish Ndhlovu: Thank you. And just one last point. Just to tell people, you know, don’t get Covid.  Observe social distancing, wear a mask and get vaccinated – when available.

Phil Stieg: Before we return to our discussion with Neuropsychologist Dr. Heidi Bender, let’s take a moment to hear a first-person account from a university professor in Chicago about his experience of Covid on the brain.

Phil Stieg: Before we return to our discussion with Neuropsychologist Dr. Heidi Bender, let’s take a moment to hear a first-person account from a university professor in Chicago about his experience of Covid on the brain.

I started getting a feeling like I had a cold. That was my first reaction as I felt like I had a cold and, it wasn’t going away. And Mary Pat urged me to get in touch with my doctor. And I said, here’s what I’m feeling. And he said, well, you should just to be careful, go get a test And the next day I had the results.  … And yeah, I had it.

And up until that point I was just feeling kind of lethargic. No energy. But the next week or 10 days were  kind of hellish. I probably made a bad choice out of fear and stubbornness and didn’t check myself and didn’t go to an emergency room as it started getting bad  – that I can tough this out.  I was quite frightened.

One of the weird things was I became like hypersensitive to like the tiniest sounds.  I could not sleep. There’s like three clocks in the family room. And the ticking, you never even notice it. But when I’m asleep, it’s like it was like the twilight zone, this constant ticking, ticking, ticking.  I mean, I think that was probably the first neurological effect I felt. I never I never smelled anything, but everything I ate or drink tasted like fish oil. And that was really gross. (laugh) And everything tastes fine now, but I’m smelling marijuana all the time. Yeah. So it’s been kind of weird.

Once I started to feel a little bit better, that’s when I started trying to read some things. You know I’m just struggling with this thing. I feel myself losing focus. And I forced myself to keep reading. And by the time I get to the end of page, I realize I don’t know – I have no idea what I just read.

And this was really kind of scary for me because. I am a reader, you know, I love to read, I love to read and I love to I love to write.  I love to talk with people about the ideas that are in that are in the books I read.  So this was like – what kind of a person am I going to be, you know, if this doesn’t go away?

I joined Facebook, long haul covid group, But you know, if you read someone talking about what they’re going through and it’s something like what you’re going through at least makes you feel like you’re not singled out, out of the universe for something awful you know…

Phil Stieg: So Heidi, Have you found that people that have more severe forms of covid are more likely to develop these cognitive changes and brain fog and do the neuropsychological symptoms last longer?

Heidi Bender: So I would say yes and no. Obviously, if it’s a group that has these acute neurological manifestations, of course, we would expect like stroke or seizure or encephalopathy or whoever required mechanical ventilation, we would, of course expect a more severe and prolonged or protracted recovery course.  However, what’s really been interesting that we’ve been learning from our patients is; patients who have had relatively mild physical illnesses, don’t necessarily have mild neurocognitive symptoms. Mild doesn’t necessarily mean mild. And I think we’d be really remiss to kind of make that one-on-one correlation.

Phil Stieg: I’m curious about the you know, the patient that’s been in the ICU, the thing that we’ve noticed is once the patient ends up in the ICU and ends up on a ventilator, they’re for a very long time. Obviously, this is the more severe form, thank God, not the most common form.  What effect does being in an ICU and being on a ventilator, being isolated from your family, have on the patient independent of covid-19?

Heidi Bender: This is something that we know from decades past.  ICU delirium, disorientation, confusion, lack of cognitive arousal, lack of cognitive stimulation.  And to add on top of that, with covid-19, these patients need to be isolated in order to mitigate or minimize the spread of illness. So these patients can’t even have family members visit them.  So they have this isolation as well as the confusion, the disorientation that takes a really long time to recover.

Phil Stieg: And as a result of being in the ICU and being on a ventilator and being isolated . Are you seeing increased effects such as anxiety, depression or post-traumatic stress disorder in the covid population?

Heidi Bender: Yes, these patients who have had acute respiratory distress or have been in ICU or have had very, very complicated disease courses, have a very elevated risk of PTSD, post-traumatic stress disorder, anxiety and depression that does persist.

Phil Stieg: So tell us about what it’s going to mean for me.  I’ve had covid I’ve been on a ventilator and I’ve got to go see you. What’s going to happen? You know, give me step by step what you what you do with a patient.

Heidi Bender: You come and you see a neuropsychologist. We sit down and we talk .  We talk for an hour or more if needed. And you really tell me about your symptoms of covid. But I also really want to know not only how are you doing post covid, but tell me how you were pre Covid.  What was your cognitive functioning like? What was your emotional functioning like? What was your trauma history? Because that really has a huge predictive impact on recovery.  And we’d put you through a series of very covid specific neuropsychological tests that we know address the neurocognitive symptoms often seen in this population. So attention, or what we call executive functioning, meaning problem solving and behavioral regulation, we would also check on your language, your memory, your mood.  All of these are factors on how you are functioning now and potential targets for intervention. We then come up with a treatment plan for you.  And that treatment plan may include seeing another provider, a neuro- ophthalmologist, a neurologist, or it may include some services that we offer here within the neuropsychology division. So we do a lot of interventions as well.

Phil Stieg: I’m assuming that patients that have had covid that have brain fog and confusion aren’t going to say, “hmm, maybe I need to go see a neuropsychologist?”  So what do I, as a loving family member, number one, look out for? And number two, then what do I do?  Neuropsychologists don’t grow on trees. How do I how do I find one?

Heidi Bender: I love that question. So I think the first thing is these patients have been through a trauma both physically and emotionally and in some cases cognitively. We have to cut these patients a little bit of slack. You can’t, as a family member, expect they’re going to be the same exact person that they were pre-covid. That’s just not realistic. So I think as a family member, you have to really be supportive, non- judgmental and really help the patient see how much they’ve improved and not necessarily have them hyper focus on the areas that still need work.  That would be my first piece of advice. And then to find out, of course, I would say go to the Cornell Department of Neurological Surgery website.  But for our larger listenership, obviously you may want to find a local provider that is abreast of the literature and that has a history of treating patients who have post-covid neuropsychological symptoms.

Phil Stieg: I would suspect that aside from the fact that somebody might be isolated for a long period of time in a hospital when they get out, is there that secondary sense of isolation because “I’ve got a little bit of brain fog and nobody seems to be understanding me.” You know, “I keep complaining about this change of smell and taste and nobody wants to believe me” . How are you helping patients cope with that isolation?

Heidi Bender: I really think validating their concerns and again, I understand why people don’t believe them per se,  because we don’t have enough literature to kind of back that up to say this percentage of people have difficulty with taste.  This percent of people have brain fog. We’re sort of, in a way, making this up as we go along and learning as we go. So I understand how that could be very difficult for patients.  So in some ways group therapies or having patients come together where they can speak about both their shared and unique experiences can be a way to combat that isolation.

Phil Stieg: When you’re treating a patient, are you doing this one on one or are you doing group therapy?  Do patients meet with each other and and talk through and provide therapy to each other?  What approaches are you taking?

Heidi Bender: We’d really talk to the patient and see what their preference would be. Right, because some patients feel like they would benefit from, you know, breaking the confines of this isolation that they’ve had for so long. And it’s interesting because sometimes people say, oh, I’m a private person. I don’t really think I would be good in group. But they’ve been so isolated and they feel so marginalized by having this covid-19, because even though millions of people have it, when you’re alone in the room sick, you feel like you’re the only person in the world.

Phil Stieg: Have you found that patients have a reluctance to want to get neuropsychological therapy, cognitive behavioral therapy or cognitive remediation? Or by the time they get to you, they’ve come to terms with that and they just do it?

Heidi Bender: No, I think patients have been so incredibly receptive and unbelievably grateful that this is an option, particularly with cognitive behavioral therapy. It provides patients with coping strategies and other tools to help bolster their emotional and psychological well-being. Who wouldn’t want that after such a significant life trauma?

Phil Stieg: What have you done to destigmatize and make it more acceptable for us now to understand that the brain is like any other organ and we can do things that are not invasive, we can actually help you.

Heidi Bender: I think the first step is for patients to get comfortable with us during the evaluative process, for them to form a relationship with us, for them to see that we’re human, that we are not shrinks, that we’re not going to pick them apart psychologically.  Once they get to know us as clinicians, I think half the battle is won.  Then having them in a room with other people who are not clinicians and who have shared similar life situations with them.  To me, it really helps facilitate their engagement in the group, the buy-in and their continual attendance.  we asked the group yesterday what their feedback was so we can let everybody know on this podcast, let the listenership know. And they said that they as a whole, they no longer feel overwhelmed because they’ve been provided with strategies and interventions as taught by our neuropsychologist, to better cope with their lasting cognitive and emotional symptoms of covid-19.  And that’s huge.

Phil Stieg: You’ve been doing Covid for a little bit over a year. Any surprises? There’s something just sort of smacking you. Oh, my God, I didn’t expect this at all.

Heidi Bender: I feel like every day that we live as humans with covid is just a continual surprise. That’s never ending. But from a professional perspective, I don’t think we thought a year ago that there would be such persistent cognitive symptoms,   a constellation of emotional symptoms, and that it would touch people’s lives in such a profound way. It’s now changing workplaces. It’s now changing education directly, indirectly. There’s not a single person who covered hasn’t touched in some way.  And I think the magnitude of that continually shocks and awes me.

Phil Stieg: So what are you personally learning from the patients? And then how is that guided or changed the way you treat patients?

Heidi Bender: Oh, my goodness. It’s both exciting and terrifying and personally challenging. I can’t even tell you how much this has changed me, not only as a provider, but as a clinician.  We really have to remember the long term lasting symptoms of covid are real. And we have to listen to our patients in ways that we never have and give them the time to express how they’re feeling in a very open and nonjudgmental way.  And another thing that I think that I’ve learned is to really internalize just how much these patients lives have been changed. Patients are considered, of course, lucky that they have recovered and they can go back to their lives, but they’re in some way changed. And it’s important for us as clinicians to really recognize and honor that.

Phil Stieg: Dr. Bender, it’s been a great pleasure having you on the show. It’s clear  that there is an inner energy and an inner passion for what you do. And what I find most positive is that you are giving all of the listeners this ray of hope that there is going to be a normal life beyond covid from a neuropsychological perspective. Thank you so much for being with us.

Heidi Bender: Thank you so much, Dr. Stieg. It was a true pleasure.