Does COVID-19 increase the risk of future gastrointestinal disorders?

By Dr. Priyom Bose, Ph.D.Aug 2 2023Reviewed by Benedette Cuffari, M.Sc.

The rapid outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in the coronavirus disease 2019 (COVID-19) pandemic. Several post-COVID conditions have been reported, including those affecting the gastrointestinal system.

In a recent study published in Viruses, scientists review existing literature to examine the association between acute SARS-CoV-2 infection and the incidence of gastrointestinal symptoms.

About 50% of patients with irritable bowel syndrome (IBS) develop a concurrent mental health condition, mostly anxiety, which affects their daily life. Likewise, some patients experience low mood, depression, and anxiety as a post-COVID syndrome. The current review also discusses the physical and mental disease burden associated with both post-COVID syndrome and gastrointestinal illness.

Study: A Systematic Review of the Prevalence of Persistent Gastrointestinal Symptoms and Incidence of New Gastrointestinal Illness after Acute SARS-CoV-2 Infection. Image Credit: SHISANUPONG1986 / Shutterstock.com

How does SARS-CoV-2 affect the gastrointestinal system?

Several studies have reported post-COVID syndrome, or long-COVID, which persists for more than twelve weeks from the onset of the infection. Based on self-reported data from the United Kingdom, about 3.3% of the general population developed long-COVID as of January 2023.

Various gastrointestinal symptoms including diarrhea, dysgeusia, anorexia, nausea, and hematemesis are frequently reported in patients who have been infected with SARS-CoV-2. Notably, dysgeusia and diarrhea are common long-COVID symptoms. 

A wide range of pathophysiological mechanisms have been proposed to explain how SARS-CoV-2 infection impacts the gastrointestinal system. SARS-CoV-2 binds with the angiotensin-converting enzyme-2 (ACE-2) receptor, which is highly expressed in ileal enterocytes present in the small and large intestines. This binding may decrease tryptophan absorption and impair angiotensin homeostasis, subsequently leading to inflammation and gut microbial dysbiosis. 

In many cases, alterations in the gut microbiome have been observed during acute SARS-CoV-2 infection. More specifically, a depletion of beneficial gut microorganisms and an increase of opportunistic pathogens in the gastrointestinal tract have been found in patients with acute COVID-19.

Even after recovery, microbial dysbiosis worsens over time. High levels of interferon β (IFN-β) and IFN-λ1, as well as the persistence of SARS-CoV-2 viral matter in the intestinal epithelium, have also been observed after recovery from COVID-19.

About the study

All relevant studies related to COVID-19 and gastrointestinal symptoms or illness published between December 2019 and July 3, 2023, were obtained from different databases including SCOPUS, OVID MedLine, and Europe PubMed Central. Pre-publications posted to the medRxiv preprint server were also included in the analysis.

The current review assessed all observational studies, including cohort, case-control, and cross-sectional studies. One of the key inclusion criteria is that patients included in these studies must experience ongoing gastrointestinal symptoms or new gastrointestinal illnesses beyond acute COVID-19 infection.

Study findings

After removing duplicate articles, the initial search resulted in a total of 2,549 studies, 45 of which satisfied all the inclusion criteria and were considered in the review. Taken together, these studies comprised 2,224,790 patients with persistent gastrointestinal symptoms following SARS-CoV-2 infection.

The studies were conducted in twenty-eight different countries throughout the world and reported the prevalence of persistent gastrointestinal symptoms for up to a maximum of eighteen months following recovery from COVID-19. After infection, a higher incidence of gastrointestinal illness linked to motility disorders, functional impairments, autoimmune-mediated illness, and hepatic issues were observed.

A high rate of inter-study heterogeneity was observed due to data obtained from varied settings associated with changing circumstances. Many studies have indicated that a significant number of individuals could be susceptible to persistent post-COVID gastrointestinal symptoms. As compared to controls, a higher prevalence of diarrhea, nausea, vomiting, and abdominal pain was observed in patients previously infected with SARS-CoV-2.

COVID-19 symptoms differed based on the SARS-CoV-2 variant and healthcare-seeking behaviors of the individual. One study reported that children with a history of SARS-CoV-2 infection attended the hospital’s emergency department due to abdominal pain.

A higher incidence of IBS was also found between three and six months after COVID-19. However, one study disagreed with this finding and stated that children with a history of COVID-19 are protected from developing persistent diarrhea and nausea one month following infection.

An association between COVID-19 and the development of autoimmune-mediated gastrointestinal illness has been reported by a limited number of studies. This finding is based on the molecular mimicry hypothesis. Notably, a similar rate of incidence of Clostridium difficile infection was observed between SARS-CoV-2-exposed and unexposed patients.

No evidence was obtained on the hospitalization rate for gastrointestinal infections due to previous SARS-CoV-2 infections in the older population. Thus, it is possible that the implementation of non-pharmaceutical interventions (NPIs) to restrict SARS-CoV-2 transmission also reduced enteric infections.

In some cases, oral or intravenous antibiotic treatment led to persistent diarrhea and/or dysphagia. This treatment was identified to be a strong predictor for post-COVID gastrointestinal sequelae.

Limited studies have reported an incidence of low mood among patients with persistent post-COVID gastrointestinal symptoms. However, no strong evidence could establish an association between persistent gastrointestinal symptoms and anxiety, low mood, and sleep disturbance.

Conclusions

Several studies have indicated the prevalence of post-infection functional gastrointestinal symptoms up to eighteen months after COVID-19 recovery. In the current study, as compared to the general population, a higher rate of gastrointestinal illnesses, including IBS, hepatic disease, dyspepsia, and autoimmune-mediated illnesses, was found among individuals with a history of COVID-19.