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Looking to the Future: What Are the Long-Term Effects of COVID-19?

By Tanner Jensen | July 17th, 2020

As research into COVID-19 continues, mounting evidence suggests that the disease may cause significant brain damage in some recovered patients. Some researchers have focused their attention toward the long-term effects of COVID-19 on brain health and the potential for developing neuropsychiatric conditions.

  • Common neurologic symptoms of COVID-19 include delirium, strokes, and sensory loss (specifically taste and smell)
  • Some neurological effects of COVID could be due to the body’s immune response response, rather than the disease itself
  • Some studies suggest that Alzheimer’s disease could be a significant risk factor for more severe cases of COVID

Being Patient spoke with Dr. Emily Troyer, a researcher at UC San Diego, about the potential long-term effects of COVID-19 on brain function, what we can learn from past pandemics, and what it means for those living with dementia.

How Do Past Pandemics Compare?

Being Patient: You’re studying past pandemics and what impact they’ve had on the brain. Tell us a little about the history behind your research.

Dr. Emily Troyer: It’s a really fascinating question. We actually published a paper back in April, and that was before a lot was known about COVID-19 or its effects on the brain, or the nervous system. So, really our inspiration was going back in the history book and reading about something called encephalitis lethargica. This is an inflammation of the brain that affected hundreds of thousands of people around the beginning of the twentieth century.

It happened a very long time ago, so we don’t know exactly what the cause of this was, but it occurred around the time of the last major influenza pandemic, and so we’ve always thought that this may be related to the influenza virus or to the body’s immune response to the virus that causes this inflammation of the brain.

Being Patient: Back at that time during the last great pandemic, do we know whether people were dying from neurological conditions, or was it in studying afterwards that we’re seeing more neuropsychiatric conditions?

Dr. Emily Troyer: Of course a lot of people died from influenza, but when you talk about encephalitis lethargica, we’re really talking about the delayed effects in people who survived influenza. So, we don’t think that it was a direct cause of influenza per se, because these are individuals who had it, survived, and then days, weeks, or months later started to develop other problems.

The most common problem in encephalitis lethargica is sleep disturbances, which is where it gets its name. “Encephalitis lethargica” basically means sleepy, or Sleeping syndrome, and so it was very common for people to be very tired, to sleep a lot more than usual, to seem cognitively slower, to be emotionally depressed for several years. It’s also interesting that around the same time that encephalitis lethargica was being described, Alois Alzheimer discovered neurofibrillary plaques and tangles, and there is some overlap. In some autopsy studies on encephalitis lethargica, you see accumulation of plaques and tangles in parts of the brain that are helpful for controlling movement.

And actually, encephalitis lethargica looked a lot like Parkinson’s disease. The plaques and tangles were really concentrated in areas of the brain system that make dopamine and help with movement, and that’s very similar to Parkinson’s. But it’s interesting that in pathologic studies you’re seeing Alzheimer’s-type pathology contributing to a Parkinson’s-like disease, so it is interesting.

What Happens in the Brains of People with COVID?

Being Patient: Is it normal for viruses to attack the brain?

Dr. Emily Troyer: It is normal for people with infectious diseases to experience a lot of what I’m describing. That’s because it may not be the virus itself attacking the brain, it may be the body’s immune system trying to fight off the virus. Which is helpful for the body, to fight off the virus, but it may also have some unintended side-effects for the brain.

So it is common for people who are in a hospital or in the ICU in particular to be confused and to experience a lot of the neuropsychiatric symptoms that I’ve described. What I think is different about COVID is, we wouldn’t necessarily expect any infectious illness to cause the proportion of strokes that we’re seeing in patients. We think that’s because COVID makes the blood more likely to clot, causing clotting problems all over the body including in the brain.

Being Patient: I recently talked with an ER doctor who dealt with the first wave of COVID patients, when they first started noting more symptoms in the brain. What more do we know about how COVID affects the brain?

Dr. Emily Troyer: We know that there have been a lot of neurological and psychiatric symptoms described in COVID-19 patients, and the list is really long at this point. We know that if you’re hospitalized for COVID-19, about a third of patients will have some kind of neurologic symptom. The most common is confusion, or delirium which is a confusional state. Strokes are also occurring in individuals with severe COVID-19.

Those are really the most common and severe, but it can also be something as small as just losing your sense of taste, losing your sense of smell, having a headache, feeling fatigued. The range of things that we’re seeing for COVID-19 in terms of neuropsychiatric symptoms is really broad, and we’re learning more every day.

Being Patient: Do we know how COVID is attacking the brain? What’s going on inside our brains that put them at risk if you are a COVID patient?

Dr. Emily Troyer: We really don’t know, unfortunately. We know that there are a lot of potential ways that COVID could influence the brain and influence cognition and influence behavior. With the autopsy studies that we’re seeing with COVID-19, it’s probably less likely that’s it’s the virus directly entering the nervous system. So, the virus is rarely actually getting to the spinal cord or getting to the brain.

That doesn’t mean that it isn’t wreaking havoc though, because like I said I think it’s the immune system that’s probably mediating a lot of the neurologic symptoms that we’re seeing afterwards. So, when your body mounts an immune response, you shoot off a cascade of chemicals, or inflammatory cytokines, to fight the infection, and unfortunately those can communicate with the brain or cross the blood-brain barrier and contribute to neuroinflammation.

So, I think a lot of the neuropsychiatric complications we’re seeing or may start to see over the coming years and decades are probably in some way going to be related to that neuroinflammation.

How Does COVID Affect People with Dementia?

Being Patient: Neuroinflammation is obviously not good, and when it occurs symptoms of dementia become more apparent. Are you studying this in the context of neurodegeneration?

Dr. Emily Troyer: So, we’re looking at it broadly. Inflammation isn’t good for the brain at any point in development, so we are looking at what inflammation associated with COVID-19 does for people who are at risk for neurodegenerative disorders. Does it perpetuate cognitive decline? It may also be the case that inflammation at much earlier stages of development may be an environmental factor that contributes to advance aging.

Being Patient: What is the current information on the effects of COVID on people who are already affected by Alzheimer’s and other forms of dementia? Do we know whether the virus is actually presenting itself differently in people who have dementia?

Dr. Emily Troyer: Again, this is all very new, but if you look back to just a few months ago we had a couple studies out of the United Kingdom and Italy that showed in long term care facilities, there is a higher risk of developing COVID if you have dementia. But again, those are small studies, and they’re in those long-term care facilities where maybe the risk of contracting the virus is related to being in such close quarters with other people.

But actually, a study came out of South Korea just last week that I think was very interesting. For the past several months we’ve heard a lot about how hypertension and cardiovascular disease, diabetes, etc. are risk factors for developing COVID or for having a complicated or severe case of COVID. And what the study showed was that the three biggest risk factors for death from COVID, in their hospitalized patients, were age over 70, lung disease, or Alzheimer’s disease specifically.

And so what that says to me is that it’s not just dementia broadly that could be a risk factor for COVID, although that could be true, but that Alzheimer’s disease specifically, independent of age, is a risk factor for severe COVID and possibly death from COVID, unfortunately.

Being Patient: So what is your study looking for, what piece of the puzzle are you trying to solve?

Dr. Emily Troyer: Yeah, so I use the term “neuropsychiatric” to really mean anything that involves the brain. In modern medicine we kind of put neurology in one corner and psychology in another, but at the end of the day they’re both dealing with brain disorders. So what we were really interested in was if COVID can influence the brain, or if the immune system can influence the brain after COVID, what could happen? That could be neurologic diseases or psychiatric disorders like depression, anxiety, PTSD, as well as conditions that have symptoms of both like neurodegenerative disorders.

So what we’re doing right now is getting measures of cognitive function and psychiatric domains like depression, anxiety, and trauma-related symptoms in aging adults in the community in San Diego who may not have been personally infected with COVID-19, but who are just living through the stress of the pandemic. And I think that brings up the other side of the coin that it’s not just about what the virus is doing to the body and brain, but even if you don’t get the virus what are the effects of the pandemic on neuropsychiatric symptoms?

Edited for clarity

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