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Examining the Frequent Neurologic Manifestations and Encephalopathy-Associated Morbidity in COVID-19 Patients
A study led by Igor Koralnik, MD, chief of Neuro-infectious Disease and Global Neurology in the Department of Neurology, found that 32 percent of hospitalized COVID-19 patients experienced encephalopathy, leading to significantly worse outcomes. The Northwestern Medicine study, published in the Annals of Clinical and Translational Neurology, is the first to examine the frequency and severity of neurologic manifestations in patients hospitalized with COVID-19 in the United States. In this episode of Better Edge, Koralnik, who also leads Northwestern Medicine's Neuro COVID-19 Clinic, explains the results of the study and discusses his clinic's unique approach to treating COVID-19 "long haulers."
Featured Speaker:
Learn more about Igor Koralnik, MD
Igor Koralnik, MD
Igor Koralnik, MD is the Chief of Neuro-infectious Disease and Global Neurology in the Department of Neurology.Learn more about Igor Koralnik, MD
Transcription:
Examining the Frequent Neurologic Manifestations and Encephalopathy-Associated Morbidity in COVID-19 Patients
Melanie: Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole, and I invite you to listen as we examine the neurologic manifestations in patients hospitalized with COVID-19. Joining me is Dr. Igor Koralnik. He's the Chief of Neuroinfectious Diseases and Global Neurology and he's a Professor of Neurology at Northwestern Medicine.
Dr, Koralnik, it's a pleasure to have you join us again today. You recently published a first of its kind study in the Annals of Clinical and Translational Neurology, examining the frequency and severity of neurologic manifestations in patients hospitalized with COVID-19 in the United States. Please give us a broad overview of your research. Tell us a little bit more about this study and your findings from your published recent study that really has made international news. How do you characterize the neurologic manifestations of SARS-CoV-2 infection?
Dr Igor Koralnik: We convened a neuro COVID research group during the lockdown since we understood that neurologic manifestations were going to be frequent in hospitalized COVID patients. We reviewed the 509 first consecutive patient admitted at Northwestern Medicine with confirmed COVID-19. And we found that of those, 42.2% have some neurologic manifestation at COVID-19 onset and during the entire course of their disease, 82.3%. So four out of five patients had some neurologic manifestations, which were very problematic for them.
Of those, the most frequent were myalgias, headache, encephalopathy, dizziness, dysgeusia, and anosmia. These six manifestation accounted for 91% of all neurologic problem that they had and of those, encephalopathy, which could go from mild confusion to coma was the most severe. Since the clinical outcome of this patient was poor, only one-third of the patients with encephalopathy were able to care for their own affairs after discharge, compared to 90% of all the others. In addition, encephalopathy was associated with higher mortality since 22% of those patients with encephalopathy unfortunately passed away versus only 3% of patients who did not have encephalopathy. The global level of mortality in our patient population was 9%.
Melanie: That's so interesting to hear about encephalopathy. Tell us more about the medical outcomes you observed in these patients. And what are the risk factors, if you know them, for developing it?
Dr Igor Koralnik: So we looked at the risk factors of a patient with encephalopathy and noticed that patients who were male, older age and had other comorbidities including prior neurologic problems or stroke, chronic kidney disease, dyslipidemia and cardiac history were more likely to develop encephalopathy.
Melanie: Well then what's next when it comes to this particular area of study, Dr. Koralnik? What is your team working on in that regard?
Dr Igor Koralnik: So we're trying to understand what is causing those problems. And encephalopathy is probably multifactorial, including systemic disease and patients who are severely sick and intubated in the ICU may have lack of oxygenation, coagulopathy and high level of inflammation also known as the cytokine storm.
In addition, they may be a direct neuroinvasion of the brain or the meninges that leads to encephalopathy or encephalitis. And finally, there's potentially a post-infectious autoimmune mechanism that is at play. And those three different mechanisms may interplay in some of our patients. So we're trying to decipher one from the other. And we are studying in my lab the immune response mediated by T-lymphocytes in patients who are hospitalized with and without encephalopathy to understand what aspect of the immune system may be working, what may be not working, what may be confused by the virus leading to encephalopathy.
Melanie: Such interesting studies, Dr. Koralnik. What about the long haulers or those who have never been hospitalized, but suffer from similar neurological symptoms? Tell us about the Northwestern Medicine Neuro COVID-19 Clinic's approach to treating these patients. Explaining for us about long hauler patients, why are some people experiencing these types of symptoms?
Dr Igor Koralnik: Excellent question. So the Neuro COVID Clinic was open in May 2020 during the lockdown and was open initially in televisits only because we were not seeing live patients, but was open to patients from the entire United States. And since July, we've seen a mix of in-person visits and televisits.
Long haulers are self-described patients who've been exposed to COVID-19 sometime at the beginning of the pandemic and had a minor respiratory syndrome that lasted a couple of days, maybe a week with a sore throat, fever, but that was self-limited and did not require any treatment. And thereafter, they developed neurologic manifestation including muscle pain, brain fog, headache, dizziness, and trouble of taste and smell as well as intense fatigue. These are interspersed with cardiac problem, including variation of heart rate and blood pressure and GI problem like nausea and diarrhea. And these may fluctuate over time and last for weeks or months. And that's why they call themselves the long haulers.
We see many of those patients in my Neuro COVID Clinic, both patients who are SARS-CoV-2 positive either by nasal swab or by serology. But also, we accept SARS-CoV-2 negative patients because sometime the nasal swab was not available to them when they presented with a disease initially at the beginning of the pandemic or because they were negative because they're simply not shedding virus in the nasopharynx. They may also be seronegative with the blood test because we understand that this test is not sensitive enough to pick up SARS-CoV-2 antibodies in patients who have not been severely sick hospitalized with pneumonia in the ICU.
Melanie: Dr. Koralnik, one thing I find interesting as I was doing my research for this episode is that at the time when long haulers seek medical care for their symptoms, do you feel, this is your opinion, that physicians are aware enough to take seriously these complaints? Are some docs hesitant to investigate thinking that it may be psychosomatic as a result? People are afraid of COVID. Do you feel that with diagnostic tests being stringent and not always that easy to come by, should physicians be listening more closely to some of the symptoms you described by their patients?
Dr Igor Koralnik: A very common story that we hear from long haulers, especially those who test negative for SARS-CoV-2 is that they have been bouncing around from doctors to doctor, from hospital to hospital, and people don't take them seriously because the test is negative. But since, you know, we understand as the neurobiologist, neuroimmunologist, the limitation of the diagnostic testing, we have a different approach.
In addition, even if they were truly seropositive when they were infected initially at the beginning of the pandemic, they may have lost those antibodies six months later when they present to medical care, because the B cell response or the humeral immune response against the virus is not as long lasting as the T-cell response.
So what we do in long haulers as well, we consent them for immunological studies. And we measure their T-cell response against the virus, because T-cells have memory, which is long-lasting and we can interrogate those T-cell by stimulating them with SARS-CoV-2 peptides from various proteins. And we can detect a signature, an immunological signature that says, yes, that person was really exposed to the virus or, no, that person may look like a healthy control who's never seen the virus.
And in both cases, we're interested to take care of those patients because, if they actually don't have COVID-19, they may have another condition that may require treatment. And we've diagnosed people already with a rheumatoid arthritis or systemic lupus erythematosus, beginning of multiple sclerosis or aseptic meningitis. So those patients deserve care like any other patient.
Melanie: Thank you for that. As we wrap up, how will your research along with the Neuro COVID 19 Clinic's unique approach help shape long-term patient care, do you think? And please offer at this time as well your best advice or information, what you'd like other providers to take away from this episode about neurologic manifestations of COVID-19 and what's so important that you're doing at Northwestern Medicine.
Dr Igor Koralnik: This is a very important question because one of the manifestation that long haulers have is the so-called brain fog, which is described as decreased attention, memory, concentration, difficulties with multitasking and we test our patient using a cognitive test called the NIH Toolbox in the clinic, which takes 20 minutes and, gives us a good ID of where they stand compared to people their age, gender, and level of education. And if they perform poorly on the NIH toolbox tests, then we refer them to one of our colleagues in behavioral neurology, who will do a comprehensive behavioral neurological exam that takes an hour and a half. And that will lead to cognitive rehab and we have partners with the colleague at Shirley Ryan AbilityLab in order to do that, because we're really intent on making those people better and they may be different strategies according to the different cognitive domains that are affected to help them recover to their baseline.
What we've noticed is many patients have difficulties going back to work or they miss work for extended periods of time and it is going to be a very big problem in the future and we want to face it head on.
Melanie: What an important episode. Thank you so much, Dr. Koralnik. And as you find out more, please come on and join us again and update this episode anytime you'd like. Thank you so much for joining us today.
To refer your patient or for more information on COVID-19, please visit our website at NM.org/neuro to get connected with one of our providers.
And that concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. Please remember to subscribe, rate and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole,
Examining the Frequent Neurologic Manifestations and Encephalopathy-Associated Morbidity in COVID-19 Patients
Melanie: Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole, and I invite you to listen as we examine the neurologic manifestations in patients hospitalized with COVID-19. Joining me is Dr. Igor Koralnik. He's the Chief of Neuroinfectious Diseases and Global Neurology and he's a Professor of Neurology at Northwestern Medicine.
Dr, Koralnik, it's a pleasure to have you join us again today. You recently published a first of its kind study in the Annals of Clinical and Translational Neurology, examining the frequency and severity of neurologic manifestations in patients hospitalized with COVID-19 in the United States. Please give us a broad overview of your research. Tell us a little bit more about this study and your findings from your published recent study that really has made international news. How do you characterize the neurologic manifestations of SARS-CoV-2 infection?
Dr Igor Koralnik: We convened a neuro COVID research group during the lockdown since we understood that neurologic manifestations were going to be frequent in hospitalized COVID patients. We reviewed the 509 first consecutive patient admitted at Northwestern Medicine with confirmed COVID-19. And we found that of those, 42.2% have some neurologic manifestation at COVID-19 onset and during the entire course of their disease, 82.3%. So four out of five patients had some neurologic manifestations, which were very problematic for them.
Of those, the most frequent were myalgias, headache, encephalopathy, dizziness, dysgeusia, and anosmia. These six manifestation accounted for 91% of all neurologic problem that they had and of those, encephalopathy, which could go from mild confusion to coma was the most severe. Since the clinical outcome of this patient was poor, only one-third of the patients with encephalopathy were able to care for their own affairs after discharge, compared to 90% of all the others. In addition, encephalopathy was associated with higher mortality since 22% of those patients with encephalopathy unfortunately passed away versus only 3% of patients who did not have encephalopathy. The global level of mortality in our patient population was 9%.
Melanie: That's so interesting to hear about encephalopathy. Tell us more about the medical outcomes you observed in these patients. And what are the risk factors, if you know them, for developing it?
Dr Igor Koralnik: So we looked at the risk factors of a patient with encephalopathy and noticed that patients who were male, older age and had other comorbidities including prior neurologic problems or stroke, chronic kidney disease, dyslipidemia and cardiac history were more likely to develop encephalopathy.
Melanie: Well then what's next when it comes to this particular area of study, Dr. Koralnik? What is your team working on in that regard?
Dr Igor Koralnik: So we're trying to understand what is causing those problems. And encephalopathy is probably multifactorial, including systemic disease and patients who are severely sick and intubated in the ICU may have lack of oxygenation, coagulopathy and high level of inflammation also known as the cytokine storm.
In addition, they may be a direct neuroinvasion of the brain or the meninges that leads to encephalopathy or encephalitis. And finally, there's potentially a post-infectious autoimmune mechanism that is at play. And those three different mechanisms may interplay in some of our patients. So we're trying to decipher one from the other. And we are studying in my lab the immune response mediated by T-lymphocytes in patients who are hospitalized with and without encephalopathy to understand what aspect of the immune system may be working, what may be not working, what may be confused by the virus leading to encephalopathy.
Melanie: Such interesting studies, Dr. Koralnik. What about the long haulers or those who have never been hospitalized, but suffer from similar neurological symptoms? Tell us about the Northwestern Medicine Neuro COVID-19 Clinic's approach to treating these patients. Explaining for us about long hauler patients, why are some people experiencing these types of symptoms?
Dr Igor Koralnik: Excellent question. So the Neuro COVID Clinic was open in May 2020 during the lockdown and was open initially in televisits only because we were not seeing live patients, but was open to patients from the entire United States. And since July, we've seen a mix of in-person visits and televisits.
Long haulers are self-described patients who've been exposed to COVID-19 sometime at the beginning of the pandemic and had a minor respiratory syndrome that lasted a couple of days, maybe a week with a sore throat, fever, but that was self-limited and did not require any treatment. And thereafter, they developed neurologic manifestation including muscle pain, brain fog, headache, dizziness, and trouble of taste and smell as well as intense fatigue. These are interspersed with cardiac problem, including variation of heart rate and blood pressure and GI problem like nausea and diarrhea. And these may fluctuate over time and last for weeks or months. And that's why they call themselves the long haulers.
We see many of those patients in my Neuro COVID Clinic, both patients who are SARS-CoV-2 positive either by nasal swab or by serology. But also, we accept SARS-CoV-2 negative patients because sometime the nasal swab was not available to them when they presented with a disease initially at the beginning of the pandemic or because they were negative because they're simply not shedding virus in the nasopharynx. They may also be seronegative with the blood test because we understand that this test is not sensitive enough to pick up SARS-CoV-2 antibodies in patients who have not been severely sick hospitalized with pneumonia in the ICU.
Melanie: Dr. Koralnik, one thing I find interesting as I was doing my research for this episode is that at the time when long haulers seek medical care for their symptoms, do you feel, this is your opinion, that physicians are aware enough to take seriously these complaints? Are some docs hesitant to investigate thinking that it may be psychosomatic as a result? People are afraid of COVID. Do you feel that with diagnostic tests being stringent and not always that easy to come by, should physicians be listening more closely to some of the symptoms you described by their patients?
Dr Igor Koralnik: A very common story that we hear from long haulers, especially those who test negative for SARS-CoV-2 is that they have been bouncing around from doctors to doctor, from hospital to hospital, and people don't take them seriously because the test is negative. But since, you know, we understand as the neurobiologist, neuroimmunologist, the limitation of the diagnostic testing, we have a different approach.
In addition, even if they were truly seropositive when they were infected initially at the beginning of the pandemic, they may have lost those antibodies six months later when they present to medical care, because the B cell response or the humeral immune response against the virus is not as long lasting as the T-cell response.
So what we do in long haulers as well, we consent them for immunological studies. And we measure their T-cell response against the virus, because T-cells have memory, which is long-lasting and we can interrogate those T-cell by stimulating them with SARS-CoV-2 peptides from various proteins. And we can detect a signature, an immunological signature that says, yes, that person was really exposed to the virus or, no, that person may look like a healthy control who's never seen the virus.
And in both cases, we're interested to take care of those patients because, if they actually don't have COVID-19, they may have another condition that may require treatment. And we've diagnosed people already with a rheumatoid arthritis or systemic lupus erythematosus, beginning of multiple sclerosis or aseptic meningitis. So those patients deserve care like any other patient.
Melanie: Thank you for that. As we wrap up, how will your research along with the Neuro COVID 19 Clinic's unique approach help shape long-term patient care, do you think? And please offer at this time as well your best advice or information, what you'd like other providers to take away from this episode about neurologic manifestations of COVID-19 and what's so important that you're doing at Northwestern Medicine.
Dr Igor Koralnik: This is a very important question because one of the manifestation that long haulers have is the so-called brain fog, which is described as decreased attention, memory, concentration, difficulties with multitasking and we test our patient using a cognitive test called the NIH Toolbox in the clinic, which takes 20 minutes and, gives us a good ID of where they stand compared to people their age, gender, and level of education. And if they perform poorly on the NIH toolbox tests, then we refer them to one of our colleagues in behavioral neurology, who will do a comprehensive behavioral neurological exam that takes an hour and a half. And that will lead to cognitive rehab and we have partners with the colleague at Shirley Ryan AbilityLab in order to do that, because we're really intent on making those people better and they may be different strategies according to the different cognitive domains that are affected to help them recover to their baseline.
What we've noticed is many patients have difficulties going back to work or they miss work for extended periods of time and it is going to be a very big problem in the future and we want to face it head on.
Melanie: What an important episode. Thank you so much, Dr. Koralnik. And as you find out more, please come on and join us again and update this episode anytime you'd like. Thank you so much for joining us today.
To refer your patient or for more information on COVID-19, please visit our website at NM.org/neuro to get connected with one of our providers.
And that concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. Please remember to subscribe, rate and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole,