43 - Mohammad Bashashati - GI issues in Covid & Long Covid

Episode 43 of the Long Covid Podcast is a chat with Dr Mohammad Bashashati, Clinician Scientist & Internist  and Senior GI Fellow at Texas Tech University Health Sciences Center in El Paso, Texas. We chat about GI issues in both acute and Long Covid, and the huge numbers of people who present with these issues, despite it being a topic that isn't talked about enough.

We chat about DGBI (disorders of the gut brain interaction), what this means and what might help to treat and manage them.

Published study

Rome Foundation - more information about COVID-19 and GI symptoms here

Twitter hashtag for DGBI  #PostCovid19DGBI


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Transcript

Mohammad Bashashati

Jackie Baxter: Hello, and welcome to this episode of the long COVID podcast. I am delighted to be joined today by Dr. Mohammad Bashashati and we are gonna talk about all sorts of gastrointestinal problems that people have with both acute COVID and long COVID. So welcome to the podcast. To start with would you mind just introducing yourself a little bit and what it is that you do?

Mohammad Bashashati: Thank You for inviting me. I am a clinician scientist, , an internist and a senior GI fellow at Texas tech university health science center in El Paso, Texas United States. Since 2003, the focus of my clinical practice and research was on patient with functional GI and mortality disorder. My research interests have been, uh, the role of the immune system and the pathophysiology of functional gastrointestinal disorders also called disorders of gut brain interaction, or DGBI also the endo cannabinoid system as the regulators of GI mortility. Molecular and cellular mechanisms of gastroparesis and a surgical approach to gastroparesis.

During COVID 19 after seeing the impact of this pandemic on our patients and community, I, uh, decided to study COVID 19 and its effects on the GI system. I have published articles and, uh, chapters on COVID 19. 

Jackie Baxter: Amazing. So I can put links to those articles in the show notes if people are interested in following that up, but that sounds amazing.

 I mean the GI side of cOVID and long COVID is not something that is talked about very much. And yet a lot of people seem to be suffering these symptoms. It's almost like, I dunno, it's, it's a side of it that just doesn't get talked about. So are you able to talk about the GI symptoms of acute Covid and do we know what proportion of people do experience these GI symptoms? 

Mohammad Bashashati: Sure. Let me give you an introduction about the COVID 19 and it's respiratory symptoms. Then I will focus on, the GI symptoms as well. SARS coronavirus two, which is the etiology of COVID 19, mainly attacks the upper and lower respiratory tract, an infection with it presents with cough, nasal congestion, runny nose, sore throat, flu-like symptoms, as well as lower respiratory symptoms. When affecting the lungs, presenting with trouble breathing, shortness of breast, chest pain, and drop in blood oxygen levels, which in severe cases causes hospitalization, supplemental oxygen requirement and ICU admission.

With vaccination and evolving changes in the virus structure, including the spike protein and a virus genome, we see changes in a distribution of our symptoms, mainly shifting to upper respiratory symptoms. Besides all these COVID 19 may manifest with extra pulmonary symptoms affecting other organs, including the GI tract, which we will discuss more during this podcast. The GI symptoms may affect up to one third of patients with COVID 19 in the acute phase. In our recently published study on about a thousand cases with positive COVID 19 tests, the prevalence of GI symptoms was significantly higher than other literature.

In our cases of both admitted and outpatient COVID 19 cases, 45% had diarrhea in the acute phase, 35% nausea with, or without vomiting. And 30% had abdominal pain. I should mention here, that all these numbers are based on the earlier variants of COVID 19, from 2020 and early 2021. What happens with the newer variant, including Omicron yet needs to be explored, so we don't know what will happen with Omicron. 

Necrosis of the gastrointestinal tract due to clots, decreasing blood flow in a setting of shock, as well as unique histologic features such as damages to the bile ducts, suggestive of direct liver injury from COVID 19, GI bleeding, pancreatitis and mesentric pancolitis are some other GI complications of COVID 19.

I have to highlight that many of these conditions happen during the acute COVID 19, but some of them may continue chronically . 

Jackie Baxter: There's some quite big numbers in there. You mentioned a third and then 45% as well. You know, , that is a big number for something that is not really talked about that much, Isn't it? 

Mohammad Bashashati: Yeah, that is right

Jackie Baxter: so you're talking about the sort of acute phase of COVID, but we know that again, quite a big number of people with acute COVID do go on to develop long COVID. Do we know how they continue into what we now know as long COVID, and are the people that end up with GI issues as a result of long COVID - are they typically the people that experience them in the acute phase? 

Mohammad Bashashati: Uh, not all, uh, long COVID patients had GI symptoms during their acute phase. This is a very interesting question actually, GI symptoms do not continue in all COVID 19 patients. In some patients, they continue and manifest as long COVID. In our recent study on long COVID patients with GI symptoms, fulfilling the criteria for disorders of gut brain interaction, that I will define later in this podcast, 40% developed DGBI during the follow up while they did not have any GI symptoms during the acute phase of the disease. 

Jackie Baxter: That's interesting. So the, yeah, the symptoms don't necessarily cross over between the acute and the lung COVID. That is interesting. Isn't it?

Mohammad Bashashati: Yes. That is very interesting. 

Jackie Baxter: So you've mentioned D G B I - what's that post COVID disorders of the gut brain interactions. Can you explain a little bit more about what the gut brain interaction means? Does this tie into where people talk about the gut being the second brain? 

Mohammad Bashashati: Yes, of course. If I want to define the D G B I easily, I have to give you an example, IBS or irritable bowel syndrome, probably you have heard about it is the most famous DGBI or functional GI disorder.

Sometimes our patients cannot differentiate between IBS and I B D or inflammatory bowel disease. In IBS, there is no clear gastrointestinal inflammation and it's a more functional disorder where a function of the gut is impaired, presenting with abdominal pain, diarrhea and or constipation. We have to note that pain or abdominal pain usually gets better after bowel movement in these patients.

Let's now discuss what D G B I are. They are chronic GI disorders without a definite gastrointestinal anatomical abnormality. There are several DGBI, each manifesting with a cluster of symptoms. Some present with difficulty with swallowing, heartburn, esophageal pain, abdominal pain, bloating, nausea, vomiting, diarrhea, constipation, fecal incontinence, pelvic pain, and other symptoms.

These disorders are basically due to malfunction of the GI tract in paid crosstalk between the brain and the GI tract, in association with imbalanced microbiota immune system and food antigens. If we grossly examine the GI tract of these patients, we won't see any ulcer, mass inflammation or any visible abnormality.

In our body, there are two nervous systems. First one is the center nervous system, which is in the brain and a spinal cord. And the second one, as you mentioned, is the peripheral nervous system. A big component of the peripheral nervous system is the enteric nervous system located in our GI tract form consisting of 200 to 600 million neurons - it's a quite high number, large number.

Our ENS or enteric nervous system is considered our little brain or second brain. When the interaction between these two brains gets interrupted D G B I happen, or disorders of gut brain interaction happen. An older name for DGBI is functional GI disorder. The expression functional GI disorders represent functional alterations, including changes in a GI movement, secretion and visceral sensation presenting with GI symptoms, including diarrhea, constipation, nausea, vomiting, and abdominal pain and other symptoms that I explained before.

Recently experts decided to use DGBI instead of functional GI disorders in order to show the importance of the GI tract and its crosstalk with the brain in the pathophysiology of these disorders. Based on definition patients with post COVID 19 D G B I should have chronic GI symptoms, fulfilling criteria for DGBI for the last three months with symptom onset at least six months before diagnosis.

So the symptoms should be chronic. Starting six months ago is important. Also previous COVID 19 infection is important in these cases. Another important point is those who had D G B I before COVID 19, they won't be considered as post COVID 19 D G B I. So D G B I should happen after COVID 19, that we classify those patient as post COVID 19 DGBI. 

Jackie Baxter: Right. Okay. So if people had these conditions before, COVID, what about, for example, if there was somebody who had A GI issue before COVID and then developed COVID and it changed or got worse, or they developed a different one. That's a bit of a grey area, isn't it? 

Mohammad Bashashati: Yeah. SO if, uh, if they develop a different one yeah, that is considered post COVID 19 D G B I, but if their condition gets worse, it is still D G B I, but, uh, means COVID stress, anxiety, and many other things may affect their symptoms. It's already published in the literature. But It is also possible that COVID causes some changes in neurotransmitters, in brain gut signaling and inducing more effects on these disorders means causing, getting them severe or maybe adding some other symptoms to their previous symptoms.

Jackie Baxter: Yeah, of course, because we've heard lots of people say that COVID almost like it finds out your weak points and then, you know, kind of goes for them. So if you had something in a minor form before COVID then the virus is gonna seek that out and exacerbate it. It's just really annoying isn't it? It's like it prays on your weaknesses. 

Mohammad Bashashati: That's right. Yeah. 

Jackie Baxter: But yeah, that's really interesting hearing about all those different symptoms that fit under the post COVID D G B I umbrella, you know, there's a huge number of symptoms there, isn't there. 

Mohammad Bashashati: That is right. We have upper and lower GI symptoms, uh, tons of these symptoms that may make a cluster of symptoms defining DGBI 

yeah, 

Jackie Baxter: I think I hadn't quite realized. I mean, I knew, but I hadn't realized, you know, quite how big the GI sort of amount of, the things in your body that are a part of that, - there's a lot in your body that is the GI system, isn't there? 

Mohammad Bashashati: that's right. And I have to mention these DGBI have an overlap. Some patients may have functional dyspepsia, plus irritable bowel syndrome, uh, or lower plus upper. So They may have overlap and some of them may start right after COVID 19 while the patient may have some of them before COVID 19. So this is definitely considered the post COVID 19 condition. Yeah. 

Jackie Baxter: Yeah. It's really interesting isn't it? So do we know what's causing some people to develop these post COVID D GBIs - what are the sort of mechanisms? Do we know anything about that? 

Mohammad Bashashati: The underlying mechanism of DGBI, including post COVID 19 D G B, I are not well understood. Besides taking history and performing a physical exam, GI doctors rely on endoscopic x-ray imaging and laboratory tests for a diagnosis of gastrointestinal disorders. As I mentioned before, uh, all these tests will not clearly reveal a specific abnormality in D G B I. Therefore, whatever mechanism proposed in these disorders is microscopical at molecular and cellular levels.

Previous experiences with these disorders indicated that an acute event, including an infection may trigger an increased sensation of the gut. Changes in a motility and contractions versus relaxations of the gut muscle and secretion and absorption of the fluid and electrolytes in a GI tract, which will sustain after the acute event.

Let me give you an example on how infection may lead to DGBI. In May, 2000 E-coli and another type of bacteria called campylobacter jejuni contaminated the drinking water in Canada, seven people died and over 2000 were ill as a result of this contamination. After the acute phase, the incidence of post infectious IBS two years after the outbreak was 36% among those with clinically suspected gastroenteritis.

So infection led to post infection IBS in these patients. Post infection DGBI was first defined after bacterial infection, mainly gastroenteritis, but viruses may also trigger these conditions. Therefore we believe that post COVID 19 D GBI are a form of post infection DGBI, which happened after COVID 19.

Those viruses predominantly affect the GI tract causing GI symptoms. As SARS coronavirus two also affects the GI tract in the acute phase that we discussed earlier in this podcast, it's reasonable to consider post COVID 19 D G B I a post infection condition. It is possibly related to the high expression of the A C E two in the gut.

Probably you have heard about A C E two. This is a receptor that is required for SARS coronavirus 2 virus to infect human cells. The infection of the gut epithelial cells triggers an increase in changes in gut secretary function, as well as a low rate of inflammation and changes in Gut microbiota. Low grade inflammation can stimulate the enteric nerves and a gut nerves, which always have a crosstalk with our central nervous system.

These factors together with the stress of having COVID 19, anxiety, depression can generate symptoms of post COVID 19 DGBI. In fact, these mechanisms have been also described for other post-infection D G B I such as post-infection IBS. 

Jackie Baxter: Yeah. That is interesting. Isn't it? And this idea of a stressor, I mean, in this case, we're talking about COVID, but, it's almost like, you know, that feeling, if you're nervous and you're feeling a bit stressed and you get butterflies in your stomach. It's almost like sort of that, but amplified, a hundred times, isn't it? 

Mohammad Bashashati: Yeah. That butterfly in the stomach may trigger GI symptoms and that's a stress and they may lead to some problems in gut brain interraction and D G B I in the future. So that is possible that the stress. Somehow in these patients, but besides the stress we have to consider that SARS coronavirus two also attacks the GI tract and may have local effect as well is not a hundred percent in stress, but post inflammation changes in neurotransmitters and a gut signal in hormone receptors may also trigger these symptoms as Well as changes in immune cells, which may continue chronically after COVID 19 may contribute to post COVID 19 DGBI. 

Jackie Baxter: Yeah, for sure. Cos yeah. When you add the virus in, on top of everything else - you've just mentioned the virus being present, you've mentioned inflammation and something else ....I think you just mentioned that I can't remember.....and these are all things that are talked about as being the underlying cause of long COVID and, it's all connected. Isn't it? 

Mohammad Bashashati: That is right. Yeah. There is crosstalk between microbiota, immune cells, brain, gut, enteric nervous system. All of these may lead to D G B I including post COVID 19 D G B. The mechanism is not simple. 

Jackie Baxter: No, not at all. And it seems to be different for different people as well, maybe 

Mohammad Bashashati: that is right. So that's why some people, they get it. And some people after recovering from COVID 19, they don't get D G B I. 

Jackie Baxter: Yeah, of course. Yeah. Everyone's different, which is both beautiful and frustrating when you're trying to nail down what's causing things, I guess.

Mohammad Bashashati: Yeah. 

Jackie Baxter: We talked earlier about the numbers of people that were having acute COVID GI issues. What do we know about the incidence of the post COVID D G BI? 

Mohammad Bashashati: Okay. We have limited studies on this area. A recent study from India and Bangladesh has reported that 9% of 288 adults with COVID 19 infection developed DGBI.

IBS happen in 5.3% of these patients, dyspepsia or upper GI symptoms with gastric offset in 2.1% and IBS with dyspepsia overlap in 1.8% of the study subjects, at six months, post infection's important. After six months, they assess this. We are also expecting another publication from Italy, which will be come soon. 

Our study published in neuro gastroenterology and motility was a case series on patients with chronic GI symptoms at least six months after COVID 19 among 164 subjects, 66% develop symptoms suggesting DGBI. 66% after COVID 19. As I mentioned before, 14% of the post COVID 19 DGBI subjects did not have GI symptoms when they were hit by the virus in the acute phase. Symptoms suggesting functional dyspepsia presenting with upper abdominal discomfort after eating, or with upper abdominal pain where a mass come D GBI followed by IBS, like symptoms in our study. Another study from the United States evaluated 200 patients with history of COVID 19, who were followed up in a respiratory illness clinic during the first surge of COVID 19 pandemic from April to September 2020. From these 200 subjects without D G B I before COVID 19, 79 developed IBS and or functional dyspepsia-like symptoms. 58 had function, dyspepsia-like symptoms, two IBS like symptom, and 19 overlap of both functional dyspepsia and IBS. I have to mention that these studies were questionnaire based, therefore, to have a more accurate prevelence of post COVID 19 D G B I, the patients may need further work-up to rule out other organic abnormalities. 

Jackie Baxter: Yeah, of course. Yeah. And that kind of leads me into my next question because how do you diagnose them? You mentioned questionnaire based things and I guess that is useful because you can survey a large number of people by doing questionnaires, but in order to actually examine patients individually, that's gonna be a lot more difficult to do, isn't it? 

Mohammad Bashashati: That is right. So the questionnaires are good for screening and for research that you can cover many subjects in your study, but for the diagnosis of D G B, I, we have to rule out organic abnormalities first. Basically patients With D G B I present with chronic ongoing GI symptoms that necessitate further investigations. Imaging, and endoscopies and laboratory tests like blood and stool work-up are performed to rule out organic disorders.

In these patients. There are screening tools such as the Rome IV questionnaire that we use in our study. But to make the final diagnosis further tests should be performed. For example, for a diagnosis of IBS, with diarrhea as the predominant GI symptom - based on patients, age and severity of the symptoms, I may consider doing a stool workup to rule up infection with bacteria and parasites, as well as inflammation. I may do colonoscopy plus or minus upper endoscopy with random colon and duodenal biopsies. If I do not see any gross abnormality, I may do a test to rule out small intestinal bacterial overgrow or CBO test. And I may check the thyroid function. So I have to rule out all organic causes of these symptoms before labeling a patient as D G B I in my clinic. So it's totally different than the research. 

Jackie Baxter: Yeah, of course. I've certainly spoken to people and I've sort of found it myself. You know, you go to the doctors or whatever to get certain tests done. And it is generally, as you said, to rule things out. The first time I got my bloods tested, for example, I was really pleased when they said, oh, your bloods are all normal. Everything's fine. And as time went on and my symptoms were still there and my tests carried on coming back normal, it was almost like I was hoping that something wouldn't come back normal because then it would give them something to treat.

And it sounds sort of similar here. If one of these things did come back with something, then I guess you would be able to treat that because you would know what to do, whereas if it comes back and you think, well, this must be a post cOVID D G B I, what do you do then? What is the treatment for that? Or what would you do? 

Mohammad Bashashati: Treatment is challenging. Yeah. It's based on presenting symptoms and they recognize D G B I in a subject that comes to our clinic. Some patients may have multiple DGBI. So you have to use different approaches to treat all these symptoms together.

We know about D, G B I and functional GI disorders for decades. While the treatment is, as I mentioned, sometimes difficult, the treatment of post COVID 19. D G B I is not different than the other D GBI. I, it's not different. For example, I treat IBS patient with predominant diarrhea symptoms with anti diarrheall medications, antispasmodics to decrease the spasm in the gut and neuromodulators.

Sometimes I may use a short course of an antibiotic, especially in those with small intestinal, bacterial overdose placebo. If patient comes with heartburn, I may consider acid blockers. In these cases like PPIs. For fecal incontinence, I may give fibers. anti-diarrheal medications and send patients for pelvic floor training or biofeedback based on the underlying pathology.

If I see a patient with rumination syndrome who vomits, mainly undigested food, in minutes after eating, I consider breathing exercise, medication, mindfulness and relaxation exercise through using new technologies, such as virtual reality. I may use neuromodulators in these patients as well. Therefore treatment totally depends on the class of D G B I, and patients should consult their doctors for this and get help. 

Jackie Baxter: Yes, of course, because everybody's symptoms are different. 

Mohammad Bashashati: that is right. Yeah. 

Jackie Baxter: And people can have the same symptoms, but in different severities as well, or on different days of the week. 

Mohammad Bashashati: yeah. So you have to play with the medications, with the doses, and sometimes you may need to take a specific medication, sometimes not. And because of that, we may use PRN which means as needed medications in some conditions. For example, we say, if you have this specific symptom on this specific day, take this medication, if not, don't take it next day. So it depends, 

Jackie Baxter: of course. So you can be kind of reactive to the symptoms as they arrive.

Mohammad Bashashati: Yeah, exactly. You, you have to tailor the medication and treatment based on daily symptoms. 

Jackie Baxter: Yeah, I I've described long COVID symptoms as whackamole. So it is a little bit like they keep popping up and you have to kind of be a little bit reactive, I guess, to when they come up. 

Mohammad Bashashati: Yes, yes.

Jackie Baxter: You talked about quite a few treatments and stuff there for different people and different symptoms. And you've obviously seen a lot of different people with different symptoms. Do people respond to these treatments and do they start to recover from the, the DGBIs? 

Mohammad Bashashati: Uh, we still don't know. We don't know what will happen. We need time to see how it goes. But based on our experience with D G B, I, I will say these patients may need a long term therapy course. The good news is the study on post infectious IBS in Watertown, Canada, that I mentioned before. It showed post-infection IBS cases had a favorable prognosis with a spontaneous remission and recovery in most patients.

This may hopefully happen with post COVID 19 DGBI as well, but we still don't know. 

Jackie Baxter: Of course. Yeah. But that is positive. 

Mohammad Bashashati: Yeah. That is definitely positive. Yes. 

Jackie Baxter: So, there are obviously a lot of people that will be listening to this and they'll think, oh yeah, I think I've got some or all of those symptoms.

And some people will be able to see a doctor about them. And some people won't. For whatever reason, or they may not have a particularly supportive doctor in some people's cases. Is there anything that people can do to sort of self manage their symptoms in the meantime? And I know that will be a bit vague because obviously we're talking about a lot of different people and a lot of different symptoms 

Mohammad Bashashati: yeah. I suggest that they get help from their doctors first. It is very important. Because there are some misleading information in the internet, but they have to discuss with their doctor if before doing any lifestyle specific change or take any remedies for their condition. If their symptoms, then they must try to be seen by gastroenterologists and neuro gastroenterologists who are expert in this.

There are natural remedies. And lifestyle techniques to have with these symptoms. For example, for patients with reflux-like symptoms who come with heartburn, they should avoid food with high acid or in some of them they have to avoid caffeine or decrease the amount of caffeine they use. 

For constipation they should consider fibers, drinking enough fluid water and doing exercise. Exercise is recommended for everything actually. Yeah. For patients with rumination syndrome, breathing exercise, diaphragmatic relaxation, and meditation will help. For those with bloating or abdominal distention, after ruling out condition like infections of this stomach, which, uh, with the bacteria, which is helicobacter pylori - after ruling out celiac disease or SIBO, they can consider low fodmap map, diet, and low salt diet, because salt has been shown to be associated with bloating in these patients. Low fodmap diet consists of elimination of certain fermentable sugars that may cause intestinal distress, slow reintroduction of them to figure out which one causes the symptoms. And the third step is continuing the diet with those, which do not cause the symptoms. So these may also help some patients. 

Yes, of 

Jackie Baxter: course. cos you can try cutting things out, but you can't cut everything out can you, because you need to eat! 

Mohammad Bashashati: That is right. Yeah. 

Jackie Baxter: Yeah. No, that's really, really helpful. And hopefully there's something useful there for people that are sitting at home and struggling, but yes, I think definitely people should seek out professional medical help where at all possible

Mohammad Bashashati: That is right. Yeah, definitely. Because on forums they recommend the specific things. To others, take this, take that, take this medication, but they might be harmful. So it's good to discuss with their doctors before doing them. Yeah. 

Jackie Baxter: Yes. Yeah, no, absolutely. There's an awful lot of people sort of trying their own remedies. Again, it's completely understandable. Cos people are desperate. 

Mohammad Bashashati: It is, they are desperate, but, but at least discuss with your doctor first. Make sure there is no harm. 

Jackie Baxter: Yes, that's definitely worth saying. Yeah. You talked a little bit about research and needing more research into this area. But what is there going on in the post COVID DGBI research arena, for want of a better word, at the moment?

Mohammad Bashashati: Yeah. There are ongoing studies on the mechanisms of post COVID 19 D GBI including changes in the gut microbiota and neuro signaling molecules. In my opinion, the major study would be finding the real prevalence of these disorders, the prognosis and whether patients would recover by time. This is very important address. 

The key point beyond research is to introduce post COVID 19 DGBI to the medical community. As I heard from some of my patients that they were ignored by their doctors or healthcare provider. For doctors who see patients with D G B I from now on it is important to have history of COVID 19 in each patient recorded.

In other words, from now on, if they diagnose a case with D G B, I, they should simply ask "were you infected with COVID 19. And did these symptoms start after COVID-19". That will help the patients. Also will enrich our databases with those who are affected providing enough material for the future research.

Jackie Baxter: Yeah, definitely. Because like you were saying earlier, there are people that six months on from their COVID infection do start to develop some of these things. So it doesn't necessarily happen straight away. 

Mohammad Bashashati: So we have to recognize this condition. And doctors should know about it and we should help patients to get better. And, uh, it providing enough information. 

Jackie Baxter: Yeah, definitely. And I guess as time goes on and you know, cases have been very high recently, there are a lot of people that have been infected with COVID. So it will be interesting to see with time whether the incidence of this does continue at sort of similar levels.

Mohammad Bashashati: So some of these post COVID 19 DGBI studies that I mentioned Were from earlier phases of COVID 19. So what'll happen with new variants of the virus. We still don't know. 

Jackie Baxter: Yeah, it will. It'll be very interesting to see. So, yeah. Thank you so much for chatting to me today. It's been absolutely fascinating to hear all about the GI symptoms.

So thank you for that and thank you for all that you're doing. 

Mohammad Bashashati: Thank you. Thank you for inviting me.