Since the beginning of the COVID-19 pandemic, researchers have consistently observed high rates of gastrointestinal (GI) symptoms in patients with SARS-CoV-2 infection. Study data has shown that up to 30% to 60% of this population has experienced symptoms such as nausea, vomiting, diarrhea, and abdominal pain during the acute infection, and emerging data suggests persistent GI symptoms and disorders of gut-brain interaction (DGBIs) long after the infection has resolved.1,2
In a prospective, multicenter study (GI-COVID-19) published online in Gut in December 2022, Marasco et al examined the prevalence of DGBIs following SARS-CoV-2 hospitalization to elucidate the effect of COVID-19 on the GI tract. The final study sample consisted of 614 patients with COVID-19 and 269 control participants without COVID-19 diagnoses. Researchers evaluated patients at the time of hospital admission and following hospitalization at 1, 6, and 12 months.3
Compared with control participants, COVID-19 patients showed a higher prevalence of GI symptoms (39.7% vs 59.3%; P<.001) at enrollment, and higher rates of irritable bowel syndrome (IBS) per Rome IV criteria (0.5% vs 3.2%; P =.045) at the 12-month follow-up. COVID-19 patients also demonstrated roughly twice the prevalence of depression at the 6-month follow-up, as assessed via the Hospital Anxiety and Depression Scale, compared with control participants.
Additionally, researchers noted significant associations between IBS diagnosis and a history of allergies, dyspnea, and chronic use of proton pump inhibitors (PPIs).
Patients with COVID-19- related IBS often suffer from other non-GI issues such as fatigue, insomnia or hypersomnia, chest pain, cognitive disturbances, or arthralgias.
For further insights regarding these findings and post-COVID-19 IBS in general, we interviewed Madhusudan Grover, MBBS, physician and researcher in the department of gastroenterology and hepatology at Mayo Clinic in Rochester, Minnesota, and Matthew Hoscheit, MD, physician and researcher in the department of gastroenterology, hepatology, and nutrition at Cleveland Clinic in Cleveland, Ohio.
In a 2022 study published in the journal Gut, Marasco et al noted the development of new IBS was strongly associated with dyspnea during the acute phase of COVID-19 infection, history of allergies, and the chronic intake of PPIs.1 Can you discuss how these factors may mechanistically contribute to the development of post-COVID-19 IBS?
Dr Grover: There is some literature to suggest that atopy might be associated with food intolerances and IBS. Moreover, a recent study showed that a prior infection might induce loss of immune tolerance and a gut-localized allergic response.4 PPI use can induce small bowel or colonic dysbiosis, which may predispose individuals to the development of postinfection IBS.
The association with dyspnea is interesting. Dyspnea can be seen as a marker of COVID-19 severity, which can result or associate with greater intestinal injury and increased permeability, both of which are known to increase the predisposition for IBS development.
Dr Hoscheit: Authors of this study provide important insight into the risk factors for post-COVID-19 IBS. Another important factor to consider is that this study examined patients who were hospitalized with the COVID-19 infection rather than those with COVID-19 who did not seek medical attention. This may also indicate that a more severe COVID-19 infection is a risk factor for post-COVID-19 IBS. Further study may help clarify this point.
The pathophysiology of post-COVID-19 IBS and other GI manifestations of the disease is incompletely understood and likely multifactorial. Enterocyte invasion by the COVID-19 virus leads to a cascade of inflammatory responses, leading to intestinal dysbiosis. The increased risk of developing diabetes following infection can lead to GI dysmotility. Altered taste and smell, visceral hypersensitivity, and autonomic dysfunction also play an important role in GI dysfunction following COVID-19 infection, which can lead to a variety of symptoms.
PPIs can cause changes in gut microbiota, which may lead to GI symptoms, but PPIs can also increase the risk for infection if used during COVID-19 infection.3 Are there any alternative and complementary medicine practices that clinicians can recommend to patients currently prescribed PPIs?
Dr Grover: The use of PPIs should be judicious, and clinicians should consider weaning these agents when they are not clinically indicated. It is established that the use of PPIs can influence the intestinal microbiota composition,3 which can have deleterious primary and secondary effects — as when the gut is challenged with an injury or infection. Dietary and lifestyle modifications can work in a substantial number of patients with mild-to-moderate heartburn symptoms. Routine or “preventative” use of these agents often results in overutilization for nonindicated reasons.
Dr Hoscheit: PPIs are some of the most commonly used antisecretory medications for heartburn, gastroesophageal reflux disease (GERD), and other upper GI pathologies. It is important, however, to be aware of and educate our patients on the side effects of these medications, including vitamin B12 deficiency, electrolyte abnormalities, and increased risk of enteric infection.
In individuals who decline PPI therapy or for whom the risks outweigh the benefits, a variety of alternative therapies and practices exist. Lifestyle modifications including left-lateral sleeping position, elevating the head of the bed when sleeping, avoidance of problematic foods, and avoiding a recumbent position after eating are low-risk, high-reward behaviors for heartburn.
Alginates or bicarbonate-based medications serve as useful alternatives to PPIs.
In-depth conversations with our patients regarding available alternatives will allow them to select the practices that best serve their needs.
Can you elaborate on strategies used to manage post-COVID-19 IBS symptoms, such as dietary modifications, targeted supplementation, and lifestyle support?
Dr Grover: Currently, no therapies have been specifically tested for post-COVID IBS, and treatment should be [the] same as treatment for IBS in general. The American Gastroenterology Association has recently published guidelines for IBS treatment.5 Generally, postinfection IBS is either diarrhea-predominant (IBS-D) or mixed type (IBS-M), and a very small minority has constipation-predominant IBS (IBS-C). Interestingly, the study by Marasco et al also showed that 12 months post-COVID-19, constipation and hard stools were less prevalent in COVID-19 cases than control [individuals].3
A single US-based clinical trial has shown efficacy of glutamine over placebo for postinfection IBS patients with increased intestinal permeability.6 It is plausible that glutamine might also help GI patients with post-COVID-19 IBS, but this needs to be formally established. Psychological stress has also been shown to predispose and associate with postinfection IBS just like seen in this study, where depression was more common in those with COVID-19, so addressing those issues may also help improve coping with IBS and overall quality of life.3
Dr Hoscheit: A multidisciplinary approach is required for individuals with IBS, regardless of its etiology or subtype. Most importantly, establishing a clear diagnosis of IBS and discussing it with our patients allows for the development of a productive physician-patient relationship from which therapy can move forward. Another critical aspect of caring for these patients is a clear understanding of their specific symptoms, as individuals with IBS have a variety of experiences with the illness.
Many of the therapies available for post-COVID-19 IBS have been adapted from algorithms used for the treatment of nonpost-COVID-19 IBS. We are fortunate to have excellent evidence-based recommendations from our GI societies. Dietary modifications such as a high-fiber diet, low FODMAP diet, gluten-free diet, and low-carbohydrate or selective elimination diets should be considered. The FODMAP diet, given its complexity, should always be performed with physician or dietician oversight.
Antispasmodics, neuromodulators, and brain-gut therapies also play important roles in the treatment of IBS. Lastly, I encourage all my patients to maintain a normal circadian rhythm, get adequate sleep, and exercise as tolerated.
Do these treatment strategies vary among patients who have developed IBS via different means?
Dr Grover: As outlined above, generally the treatment of postinfection IBS is similar to that of general IBS. In addition to addressing the gut symptoms, it is quite useful to help patients understand the possible connection between their acute illness and the development of chronic gut symptomatology. In studies following large outbreaks of infectious gastroenteritis, a subset of patients tends to resolve their IBS symptoms over time. This is particularly true for viral infections like norovirus.7
Although not substantiated by studies currently, it is plausible that a meaningful subset of patients with COVID-19 might have resolution of their symptoms as they get further out from the time of their infection. Patients often find some reassurance with these outcomes data.
Dr Hoscheit: Due to the recency of the COVID-19 pandemic, our understanding of the causes and treatments of COVID-19-related diseases is evolving. While the COVID-19 study group provides important insight into hundreds of individuals with COVID-19-related IBS in this study, longer follow-up of these individuals may provide deeper insight into effective, targeted therapies.
Patients with COVID-19-related IBS often suffer from other non-GI issues such as fatigue, insomnia or hypersomnia, chest pain, cognitive disturbances, or arthralgias. The number and severity of these symptoms can significantly impair one’s quality of life. A multidisciplinary team of clinicians and providers, often achieved through “long COVID-19 clinics” provides a unique opportunity to understand and address our patients’ concerns.
- Chan WW, Grover M. The COVID-19 pandemic and post-infection irritable bowel syndrome: what lies ahead for gastroenterologists. Clin Gastroenterol Hepatol. 2022;20(10):2195-2197. doi:10.1016/j.cgh.2022.05.044
- Austhof E, Bell ML, Riddle MS, et al. Persisting gastrointestinal symptoms and post-infectious irritable bowel syndrome following SARS-CoV-2 infection: results from the Arizona CoVHORT. Epidemiol Infect. 2022;150:e136. doi:10.1017/S0950268822001200
- Marasco G, Cremon C, Barbaro MR, et al; GI-COVID19 study group. Post COVID-19 irritable bowel syndrome. Published online December 9, 2022. Gut. doi:10.1136/gutjnl-2022-328483
- Aguilera-Lizarraga J, Florens MV, Viola MF, et al. Local immune response to food antigens drives meal-induced abdominal pain. Nature. 2021;590(7844):151-156. doi:10.1038/s41586-020-03118-2
- Chang L, Sultan S, Lembo A, Verne GN, Smalley W, Heidelbaugh JJ. AGA Clinical Practice Guideline on the pharmacological management of irritable bowel syndrome with constipation. Gastroenterology. 2022;163(1):118-136. doi:10.1053/j.gastro.2022.04.016
- Zhou Q, Verne ML, Fields JZ, et al. Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome. Gut. 2019;68(6):996-1002. doi:10.1136/gutjnl-2017-315136
- Klem F, Wadhwa A, Prokop LJ, et al. Prevalence, risk factors, and outcomes of irritable bowel syndrome after infectious enteritis: a systematic review and meta-analysis. Gastroenterology. 2017;152(5):1042-1054.e1. doi:10.1053/j.gastro.2016.12.039
This article originally appeared on Gastroenterology Advisor