Walter Chan, MD, and Brian Lacy, MD, Raise Awareness on GI Issues Post-COVID19

In this podcast, Dr Walter Chan sheds light on chronic gastrointestinal issues arising as a result of COVID-19 infection.

Brian Lacy, MD, is a professor of medicine and gastroenterologist at the Mayo Clinic in Jacksonville, Florida. Walter Chan, MD, is an associate professor of medicine in the division of gastroenterology and hepatology at the Brigham and Women’s Hospital in Boston, Massachusetts.

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Transcript:

Dr. Brian Lacy:
Welcome to Gut Check, a podcast from the Gastroenterology Learning Network. My name is Brian Lacy. I'm a professor of medicine at the Mayo Clinic in Jacksonville, Florida. I am absolutely delighted to be speaking today with Dr. Walter Chan, Associate Professor of Medicine in the Division of Gastroenterology and Hepatology at the Brigham and Women's Hospital in Boston, Massachusetts. Dr. Chan is the author of a really interesting, recently published article on COVID-19 and potential long-term gastrointestinal issues.
Dr. Chan welcome. Let's begin with some simple facts to put COVID-19 in perspective. More than 600 million individuals have been infected worldwide with nearly 7 million deaths attributed to COVID-19. And in the United States alone, more than 1.1 million people have lost their lives to COVID-19. Some people believe that this is the biggest healthcare crisis the US has faced in over 100 years. Can you give us your perspective?

Dr. Walter Chan:
Yeah, well thank first of all, thank you Dr. Lacy for having me on today. Obviously COVID-19 has a very high population impact as a disease, both on the medical and psychosocial levels, as well as an impact on the global healthcare systems. In terms of the resource utilization, the interesting thing is that we're really witnessing the evolution of a newly discovered illness and really how our body and our immune system react and adapt to them. The challenge is that there's not a lot of data, especially in the beginning. We have to use a lot of experience from what we know from other known illnesses and try to navigate as new data emerge.

So the important part of it, especially for a healthcare provider, is really to really how do we continue to practice evidence-based care, while providing care with a lot of unknowns? And I think that's a lot of the big part of the challenge in managing this condition and also patients who may be suffering from symptoms related to COVID-19.

Dr. Brian Lacy:
Absolutely. That's a great perspective. And so for our listeners who may not be quite as familiar or facile with this topic as you are, how does COVID-19 affect the GI tract?

Dr. Walter Chan:
Yeah, so COVID-19 is caused by the SARS-CoV-2 virus, and the way it actually affects our body is that it binds to these proteins called Angiotensin-converting enzyme 2 or ACE2. They have these spike proteins on the virus that bind to these ACE2 to allow them to get into the cells of our body. And the way, the interesting part of this is that ACE2 is actually very prevalent on the GI tract. There's a high expression of ACE2, particularly in a small bowel and colon. Actually, if you look at some of the experiments, there are a lot more of these ACE2 in the GI tract than there are in the lungs, even though a lot of patients come into the hospital initially, because of respiratory issues and symptoms. And once these viruses get into our cells through these ACE2 protein, they can cause a number of different impact.

It can cause direct cytotoxic effect, meaning that it can cause cell death, or injury to the cells themselves. It can cause dysregulation the random angiotensin system, which can lead to a lot of tissue injury or inflammation. It can cause cell damage to the endothelium, so it can cause a lot of vascular and thrombo inflammation issue. And finally, it can also cause a lot of dysregulation in immune system leading to an abnormal immune response. That's why a lot of patients develop these systemic immune reaction, leading to a lot of multisystem symptoms.

Dr. Brian Lacy:
Walter, I like the way you highlighted that they're actually more receptors in the GI tract than the lungs. I think that is surprising to many providers and many patients. And so recognizing that a lot of other viruses, the GI tract can be affected by COVID-19. What are some of the most common GI symptoms after a COVID-19 infection?

Dr. Walter Chan:
So some of the most common symptoms, especially in the acute phase of COVID-19, are actually very similar to what we see in a lot of viral GI illnesses. Diarrhea is one of the most common symptoms, can affect up to about a third of the patients. Nausea and vomiting is another very common symptom as well as abdominal pain. I think the interesting part of it, especially during acute illness, is that for some patients this could be the only complaints that they have from the COVID infection. In fact, in the study that we did, about 9% of patients came in with just GI symptoms, and the GI symptoms can be the predominant symptoms in another 11%. And for a lot of patients this can also be the initial manifestation. They can develop GI symptoms before they have any respiratory symptoms or even develop symptoms like fever. So recognizing these type of GI symptoms is important. We want to have early diagnosis so they became early intervention for patients who are infected with COVID-19.

Dr. Brian Lacy:
So Walter, in this very nice article you co-authored with Madhu Grover, you kind of distinguish a little bit between acute and chronic symptoms. And you mentioned that 29% of COVID-19 survivors report at least one new chronic GI symptoms six months after their COVID infection. What are some of these most common chronic typical post-COVID issues we're going to be dealing with?

Dr. Walter Chan:
Yeah, a lot of these symptoms actually are very similar to some of the most common symptoms where patients come to the GI clinic and see us. The most common ones are constipation and diarrhea. About 9% of patients can have abdominal pain. In fact, within this group of patient in their study, over a third of them eventually met criteria for IBS, the Rome IV criteria for IBS. Some patients also come in with heartburn, as well as nausea and vomiting.

In this study that they... this survey study that they did, about 11% of patients reported their GI symptoms at their most bothersome current symptoms even six months after the initial COVID infection. So it could affect a substantial number of patients.
And there's also interestingly, one other ST survey study that was done with a found that about 16% of patients after the COVID infection cannot persistent GI symptoms. And you can contrast that with what we commonly see with post-infectious IBS and the number that's often quoted is about 10% of patients after a viral or bacterial infection can develop post-infectious IBS. So in some survey study, it shows that maybe the prevalence is even higher than what we typically see with other non-COVID infections.

Dr. Brian Lacy:
So a good teaching point for our providers is that given the prevalence of COVID, we're probably going to be seeing more of these post-COVID, post-infection, dyspeptic patients and IBS patients. Walter, you gave such a nice description of the acute pathophysiology of COVID affecting the GI tract, but what's the mechanism underlying these chronic symptoms that's not ongoing infection? What really happens?

Dr. Walter Chan:
Yeah, I think we're still trying to learn in terms of what's causing these chronic symptoms, but we believe that a lot of the mechanisms are similar to the potential mechanism underlying other post-infectious IBS, or post-infectious functional symptoms. For example, it can lead to ultra motility. It might change intestinal microbiome leading to a lot of these abdominal symptoms. It can cause visual hypersensitivity, it might change intestinal permeability because of the cell damage that it can cause. Central sensitization oftentimes are very common in patient post-infectious functional symptoms.

I think some of the more COVID specific mechanism potentially are these immune dysregulation that we see, so patient can develop autonomic dysfunction. That's been reported quite a bit in patients with prolonged COVID symptoms. We know that a lot of COVID patients have altered taste and smell as part of the manifestation. So that in itself can sometimes be linked to some GI symptoms and alterations in their eating.

We also know that a lot of the metabolic dysfunction, things like diabetes have been associated with COVID. And these can also affect GI tract functions leading to a lot of the functional symptoms, or GI symptoms that we can see chronically.

There are also a lot of other factors. For example, psychological stress there have been studies that have shown that patients who have increased in depression anxiety symptoms related to the COVID pandemic might have more GI symptoms. And together with the fact that there are a lot of social changes including more isolation, basically patients who are self-isolating, or confined because of the pandemic, might have increased in psychological stress, that can increase their GI symptoms. And finally that can also lead to a lot of dietary and other behavioral changes related to the pandemic and confinement. So people might eat less healthily, may exercise less, and which can also lead to more GI symptoms as well.

Dr. Brian Lacy:
Incredibly complicated, nicely outlined, and we could even assume, but we don't know that it's probably different in different people for some of those reasons you've just mentioned. And so thinking about this and our listeners, and our patients, can we predict who will develop these chronic GI symptoms? Is it that young woman with a lot of stress, or is it that older man who has a lot of comorbid conditions?

Dr. Walter Chan:
Yeah, there have been a number of studies trying to look at what are some of the factors associated with these long-term GI symptoms. There are a few common themes that came up. It seems like patients who had GI symptoms during their acute illness are much more likely to have chronic GI issues afterwards. Patients who have underlying depression, anxiety, or other mental health symptoms either before the COVID or develop after COVID are also more likely to have these chronic GI issues. Patients who have more severe disease, basically patients who need to be hospitalized for the acute COVID infection also are more likely to report chronic GI issues afterwards. Patients who have loss of smell and taste as their initial symptoms are also another group that seem to have more chronic GI issues afterwards.

Interestingly, the studies didn't really show any gender pre-election between male and female. It seems like they're fairly evenly distributed among both genders, unlike post-infectious IBS, which is often more commonly seen in women. So that might be one of the features that's a little bit different from the post-COVID GI issues. But in terms of who is more likely to develop it seems like patients who have more severe disease, more GI symptoms, more psychological comorbidities, other ones are at higher rates.

Dr. Brian Lacy:
Wonderful. All right. So let's take that younger patient who's stressed, a little anxious, has lost sense of taste and smell and has more significant GI symptoms at the onset. What can we do to prevent those chronic issues from developing 6 and 12 months later? Any research in that area?

Dr. Walter Chan:
So unfortunately, there's not a whole lot of research that had specifically look at what can prevent development of chronic GI symptoms. But because we know what the risk factors are, including having more severe illness in the beginning and requiring hospitalization, some of the thing potentially that can help is basically shortening the duration of disease and decreasing the severity of illness.

So for example, vaccination helps prevent the disease in the first place, but also help decrease the severity, using certain antivirals may help reduce the severity of illness, decrease the duration of illness, which may also help. Continue eating a healthy diet, exercising are some of the other things that can help because we know that those would help reduce the amount of GI symptoms and IBS symptoms on their own.

There are some thoughts about what about other supplements or probiotics? Their role is still pretty unclear. It's unclear for even non-COVID related post-infectious IBS symptoms, but it's even less clear for the COVID related symptoms long term. So there's really no evidence to show that they might be helpful.

Dr. Brian Lacy:
Wonderful. And so Walter, recognizing that we're still learning just so much about this disorder, what do you think is the natural history of post COVID chronic GI symptoms? Will, these symptoms just fade away with time.

Dr. Walter Chan:
No, I agree. I think we're still learning a lot about that and there's really not much data on a natural history right now, partly because it hasn't even been that long since this illness has been discovered. But we all know that post-infectious IBS or post-infectious disorder of governing interaction often improve over time. So possibly, we can assume similar natural history for most patients with COVID, especially when their other COVID symptoms improve, like with improvement of the smell and taste or if they start eating better of their other COVID symptoms improve.

I think the ones that might be triggered to predict if they actually have other systemic dysregulation that is persistent after COVID. For example, patients who develop auto autonomic dysfunction or POTS after the COVID may be less likely to have an improvement over time on its own, and may need more management. But I think this is a question that needs a lot more research to see. And we basically just need a longer observation, longer duration with our experience with this illness to understand their true natural history.

Dr. Brian Lacy:
And I think I share your optimism and that hopefully for many of our patients with more mild disease, this will just slowly fade away with time. And so of course the loaded question is how do we treat these patients? Is there some magical solutions, some magic bullet that we can treat all these patients either with a diet or medication to improve or resolve their symptoms?

Dr. Walter Chan:
The biggest challenge is that there's really currently no high quality or randomized study on treatment for post-COVID GI symptoms. So a lot of what we do is we are just extrapolating from how we manage post-infectious IBS or other post-infectious disorder of gut, brain interactions. For example, starting with lifestyle I improvement, improving sleep, improving exercises, dietary interventions in adopting a high fiber diet or a low FODMAP diet, or some other dietary changes that we do for IBS, maybe employing symptom-based pharmacotherapy, targeting either nausea, or diarrhea, or constipation. Neuromodulators will be useful especially for a lot of pain based type symptoms.

But then the other non-pharmacological intervention like psychological therapy, cognitive behavioral therapy, gut directed hypnotherapy may be useful, especially for those who might have underlying anxiety and depression. There's still a lot of question mark as we mentioned regarding things like probiotic. There's some low quality data that suggests that maybe it could be helpful, although it's really not conclusive right now.

There's also some data in a post-infectious IBS population. I'm using glutamine as a way for treating altered intestinal barrier. I think that also certainly needs more data, but it's another possibility in the future as well.

Dr. Brian Lacy:
Walter, I like the three great teaching points you have made. You've made so many, but three great ones for our listeners stand out. One, don't forget to ask about sleep, because we know that sleep changes and lowers sensory thresholds, whichmakes you feel worse. Two, target the predominant symptom. Finally, ask your patient what's your most bothersome symptom?

And then don't be afraid to use what we used to call complementary therapy such as CBT or hypnotherapy, but they're actually mainstream, not even complimentary. So Walter, this has really just been a wonderful conversation. I've learned so much from you. I'm sure our listeners have as well. Any last thoughts for our listeners?

Dr. Walter Chan:
I think my last parting thought is that gastroenterologists and actually any healthcare provider should be aware that COVID or SARS-CoV-2 infection can result in development of chronic GI symptoms or worsening of existing GI symptoms. And they could be part of this post acute infection syndrome related to COVID. And why is that important? Is that if we can recognize that, we need to make sure that when patients come up with these symptoms who ask about potential COVID infection or exposure, especially around the time of development of their symptoms, and with that we can potentially limit unnecessary diagnostic workup, especially if patients have no other alarming symptoms, if we can really associate that with a COVID infection. And the other thing is that mainly we want to follow current known paradigms for treating routine post-infectious IBS or DGBI, given the lack of higher quality data at this point.

And my final point is that lifestyle modifications is important just like how we treat a post-infectious IBS and other DGBIs because we know that there are a lot of changes in diet and exercise and other lifestyle changes since the pandemic started. And intervention and improving that oftentimes is just as important as other interventions that we can do.

Dr. Brian Lacy:
Walter, wonderful. So to our listeners, thank you for joining in today to this segment of Gut Check, another podcast from the GI Learning Network. I'm Brian Lacy, Professor of Medicine at Mayo Clinic in Jacksonville, Florida, and absolutely delighted to have Dr. Walter Chan, Associate Professor of Medicine at the Brigham Women's Hospital in Boston, Massachusetts. Joining us here today to talk about post-COVID issues. Thank you again for joining us and we look forward to having you join us for another Gut Check podcast in the near future.

Dr. Walter Chan:
Thank you for having me.