Long COVID symptoms may involve the body's autonomic nervous system

Host Amber Smith: Upstate Medical University in Syracuse. New York invites you to be "The Informed Patient" with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith.

A number of patients who survive COVID infection struggle with a variety of symptoms long after they've recovered from the infection, and some of those symptoms are related to the body's autonomic system. Here with me to talk about his research on this subject is Dr. Ahmed Eldokla. He's a neurologist at Upstate who specializes in neuromuscular medicine and autonomic disorders. Welcome back to "The Informed Patient," Dr. Eldokla.

Ahmed Eldokla, MD: Hi Amber. How are you doing?

Host Amber Smith: Great. Now you and your colleagues have examined the association between long COVID syndrome and autonomic dysfunction. But before I asked you more about that, can you explain dysautonomia, what that is?

Ahmed Eldokla, MD: So simply it means dysfunction, or a problem in the autonomic nervous system. The autonomic nervous system is a part of the peripheral nervous system that regulates involuntary -- without a person's conscious effort -- regulates many parts of the human body, blood pressure, heart rate, body temperature, digestion, metabolism, production of body fluids, like saliva, sweat, tears, urination, defecation, and sexual response.

Host Amber Smith: So these are all things that happen without us controlling or even knowing?

Ahmed Eldokla, MD: Absolutely.

Host Amber Smith: Okay. And then by long COVID, we're talking about people who've recovered from COVID, but then they're still having symptoms more than a month after they've recovered, is that right?

Ahmed Eldokla, MD: Absolutely. Yes. So long COVID is defined as or refers to symptoms that developed or persisted at least four weeks after the onset of acute COVID 19 infection. Long COVID symptom encompasses many symptoms, including shortness of breath, headache, memory changes, nausea, abnormal sweating, palpitation, anxiety, depression, fatigue, chest pain, and also orthostatis intolerance. Many of those symptoms are seen in patients with autonomic dysfunction.

Host Amber Smith: You said orthostatic...

Ahmed Eldokla, MD: intolerance... which means, simply, lightheaded when you stand up, dizziness when you stand up.

Host Amber Smith: Well, now, if I understand correctly, for the study that you were involved in, there was a questionnaire for patients who came to a post COVID clinic at a hospital in Egypt. What did that questionnaire ask?

Ahmed Eldokla, MD: So the questionnaire is called Composite Autonomic Symptom Score 31. We usually referred to as COMPASS-31 questionnaire. It is a very dated and widely used the questionnaire to quantify autonomic symptom severity. It consists of 31 questions regarding different parts of autonomic nervous system. And answers are scored anywhere between zero to a point, which would be 1, 2 or 3, and a score was obtained by adding together points to give a total score ranging from zero to a hundred. I'll give you examples: In the past year, have you ever felt faint, dizzy or had trouble thinking soon after standing up from a sitting or lying position? When standing up, how frequently do you get these feelings or symptoms? Does your mouth feel dry? Have you had trouble focusing your eyes? And so on, and so on. 31 questions.

Host Amber Smith: What can you tell me about the 320 patients who participated?

Ahmed Eldokla, MD: So patients were included in this study if they were above 18 years old, symptomatic at COVID-19 acute phase, regardless of the severity of the symptom or the need for oxygen or ICU support, and had a confirmed diagnosis by PCR (polymerase chain reaction testing) or antibody testing, and they should have symptoms for long COVID that developed or persisted at least four weeks after the onset of the illness.

Host Amber Smith: So were they men or women in the study?

Ahmed Eldokla, MD: About 73% were female, and 27% were male. Age ranges from 18 to 74 years, with a mean of 35.9 years. Most patients, 90%, had a diagnosis of covered for more than 12 weeks, with a mean duration of 42 weeks.

Host Amber Smith: So with three quarters, roughly, of your sample being female, do you think that means that more women are affected by long COVID?

Ahmed Eldokla, MD: It seems like more women affected by long COVID, yes.

Host Amber Smith: Do you have any idea why the virus affects some people one way and other people another way, because patients are not having all of those symptoms. You've got some patients with these symptoms and some patients with these other symptoms is that right?

Ahmed Eldokla, MD: That's that's correct. That's absolutely correct. I think no one knows for sure, but I think people's immune response to infection, rather than the virus itself, that determines who is at the greatest risk from COVID-19. I also think that genetics play a role as does gender, too.

Host Amber Smith: Genetics and gender, in what way? What symptoms affect women, versus what symptoms affect men?

Ahmed Eldokla, MD: It's not clear, but there is some research that estrogen may help women against the severe disease.

Host Amber Smith: So would that protection apply only to premenopausal women? In other words, after the estrogen starts to decline, after menopause, do those rates change?

No. It is really female, no matter what age. And actually you see this also in autoimmune disease. So like people who have lupus, you see most of them are female. So any autoimmune disease, or most autoimmune disease, affect the female more than male. Now, what dysautonomia symptoms were most common among the participants in the study?

Ahmed Eldokla, MD: So many symptoms, I'm going to mention some of those: bloated feeling after a meal, vomiting, cramping, colicky, abdominal pain, bouts of diarrhea, a change in the skin color, dry eyes or dry mouth, feeling dizzy soon after standing up from a seating or lying position, trouble focusing your eyes, and sensitivity to bright light. Those symptoms are just an example.

Host Amber Smith: Do you have any prediction for whether these symptoms will get better with time?

Ahmed Eldokla, MD: That's a good question. This study doesn't address that question specifically. However, in our practice, we see these symptoms improve with time, but not necessarily resolve completely.

Host Amber Smith: What is the treatment, or is there a treatment? Is there a way to accelerate getting rid of these symptoms?

Ahmed Eldokla, MD: The treatment usually is directed to the symptom itself. We call it symptomatic treatment, meaning we mainly treat the symptoms. For example, if the patient has lightheaded or dizziness, when his stands up, we encourage him or her to drink enough fluid, exercise, and if it didn't work, we start medications that improve the blood pressure upon standing. Same thing with nausea. Same thing with the vomiting.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith talking with Dr. Ahmed Eldokla. He's a neurologist at Upstate who specializes in neuromuscular medicine and autonomic disorders, and we've been talking about patients with long COVID who come to see Dr. Eldokla to find out whether their symptoms are related to an autonomic disorder.

Do researchers understand why some people are plagued by these symptoms and some people aren't, long after the active disease has gone? Do we have a feel for why these people are affected?

Ahmed Eldokla, MD: That's a very important question. So there is not much literature that discusses etiology and the rationale of autonomic dysfunction associated with COVID. In our paper, we discussed as a possible mechanism. Let me give you some examples. COVID-19 infection in mice down-regulate the angiotensin converting enzyme two, or we call it ACE-2. The changes in ACE-2 expression or function can lead to blood pressure changes, resulting in lowering the blood pressure, which can give you lightheaded when you stand up. Scans of the brain have suggested possible COVID-19 impairment of areas of the brain that control the autonomic nervous system. For example, the hypothalamus and the brain stem, which is, which are important parts of the autonomic nervous system. COVID-19 also lead to release of a large number of inflammatory cytokines, which is a material that makes you fight the infections or inflammations. These materials can affect various body organs. For example, sympathetic nervous system is a part of the autonomic nervous system. When sympathetic hyperactivation occurs, it can cause arrhythmia, which is irregular heart rhythm, hypertension, increases sweating, reduced intestinal motility, and it can lead to serious complications, including injury to the heart.

Host Amber Smith: Do we know if vaccination status has any impact on whether someone develops long COVID?

Ahmed Eldokla, MD: We didn't look into that in this study, but I'm sure there will be more studies to discuss this question.

Host Amber Smith: Now, this particular study was focused on patients in Egypt. Is there any reason to believe you would find something vastly different among the people in the United States?

Ahmed Eldokla, MD: No, I don't think so.

Host Amber Smith: Well, I'd like to ask you about the autonomic testing that you're doing here in Syracuse for patients with long COVID who are struggling with symptoms. What does autonomic testing consist of?

Ahmed Eldokla, MD: The autonomic testing we are doing here in Syracuse consists of four parts. One -- Tilt table testing. We tilt the patient up and down and measures of blood pressure and heart rate. Two -- we measure the sweating from the legs and arms, a test called QSART or Q sweat. Three -- we ask the patient to breathe in and out, and we measure the variability of the heart rate. Four -- We ask the patient to blow in a closed tube and measure the changes in the blood pressure and heart rate.

Host Amber Smith: So, do you do all of this in one visit?

Ahmed Eldokla, MD: Yes. Yes we do.

Host Amber Smith: How long is the visit? It seems like it's pretty comprehensive.

Ahmed Eldokla, MD: It is. And actually it involves a lot of technical factors and training, but usually it takes anywhere between 60 to 90 minutes.

Host Amber Smith: So, are you able to determine, based on the results of those four tests, whether someone's symptoms are caused by COVID or, I mean, how do you tell if it's something else?

Ahmed Eldokla, MD: That's an interesting question, but to a certain degree, yes. If the symptoms started after COVID-19 infection or in association with the onset of the COVID-19, it makes sense to say that it is most likely associated with COVID. But if the symptoms started well before COVID-19 we can conclude that it is unlikely to be caused by COVID, but I have to say that all the autonomic symptoms, or most of the autonomic symptoms, can be worsened with COVID infections. And we see this all the time.

But not all the people who have symptoms really have the disease. So there is another study is going to be published in few weeks. We find only 25% of the patients who have symptoms actually have a real autonomic disease.

Host Amber Smith: Meaning autonomic disease caused by long COVID or any sort of autonomic disease?

Ahmed Eldokla, MD: Autonomic disease caused by long COVID. So they have symptoms, but they are not necessarily have the autonomic disease. So, it could be the are bedridden for a long time. It could be they're anxious. It could be are deconditioned. But only 25% of those have a real autonomic disease.

Host Amber Smith: So among the other 75%, if they don't have the disease, is it some kind of psychosomatic manifestation that they think they have it? Or are these symptoms that just pop up, and then they go away and there's nothing ever really there?

Ahmed Eldokla, MD: I think they are real. They have symptoms, but the problem is how you act with those symptoms. I will give you an example. When we are sitting down we have at least millions of receptors at work, so you'll feel the chair under you, right? But your brain ignores that. You might feel it now, when I told you you feel the chair under you, but you didn't think about it, you know? So those people who are somatic, or have more response to the symptom, it is the same thing. Their brains are not turned off. Their brain react to any small thing. So they are hyper excitable.

We believe them. They have symptoms. But this could be because of the disease itself. You are in the ICU for a long time. You know, you are thinking about everything. You're anxious. You are not moving. Imagine that you are lying in bed for a week, how you will feel. So it's not necessarily that they have autonomic disease per se, but they have symptoms that need physical therapy, deconditioning, psychotherapy, stuff like that.

Host Amber Smith: So with the 25% who it is autonomic disease, once they recover and the symptoms abate, have they got lasting damage to their autonomic nervous system?

Ahmed Eldokla, MD: So the damage can be functional. Or the damage can be anatomical, like, for example, when you have a stroke. It's anatomical damage. You have damaged certain part of the brain because you don't have enough blood supply to that part of the brain. But with the autonomic nervous system, mostly it's a functional problem. So they are not working as they used to work, not anatomical damage. So just to answer this question, simply. Most of the patients will have dysfunction or abnormal function of the autonomic nervous system that can resolve with time, but some of them will not resolve with time.

Host Amber Smith: Interesting. Now this specialized testing is not available from every neurologist. So the patients who come to you for the testing, do you see them continually or do they go back to their other doctor after the testing?

Ahmed Eldokla, MD: Mostly they go back to their doctor after the testing. The patients who are severely affected, they continue to see us.

Host Amber Smith: Okay, well, this has been very informative, and I appreciate you making time for this interview.

Ahmed Eldokla, MD: Thank you, Amber. Thank you very much.

Host Amber Smith: My guest has been Dr. Ahmed Eldokla, a neurologist at Upstate with expertise in neuromuscular medicine and autonomic disorders. "The Informed Patient" is a podcast covering health, science and medicine brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at upstate.edu/info. This is your host, Amber Smith, thanking you for listening.