Long-Term Increased Risk of Digestive Diseases After COVID-19 Infection: Study

A new study suggests people who have recovered from COVID-19—even if they had mild cases—are at risk of future digestive diseases.

UGREEN3S/Shutterstock

As COVID-19 cases continue to rise, an increasing number of people are experiencing digestive diseases. Recent research has revealed that COVID-19 infection increases the long-term risk of digestive diseases, with a notable rise even in mild cases.

A large-scale retrospective cohort study published in the BMC Medicine journal on Jan. 10 indicated that individuals previously infected with COVID-19 have a higher risk of developing digestive diseases.

The researchers included data on over 840,000 people from the UK Biobank database, categorizing them into groups: those who had been infected with COVID-19, a control group without infection during the same period, and a pre-pandemic control group using data from 2017 to 2019.

The results revealed that people who had previously been infected with COVID-19 faced a higher risk of digestive diseases compared to those who had not been diagnosed with COVID-19 during the same period. This included a 38 percent increase in the risk of gastrointestinal dysfunction, a 23 percent increase in the risk of peptic ulcer disease, a 41 percent increase in the risk of gastroesophageal reflux disease (GERD), a 21 percent increase in the risk of gallbladder disease, a 35 percent increase in the risk of severe liver disease, a 27 percent increase in the risk of nonalcoholic liver disease, and a 36 percent increase in the risk of pancreatic disease.

Additionally, the risk of GERD exhibited a stepwise increase with the severity of COVID-19 symptoms. Even one year after infection, the risks of GERD and gastrointestinal dysfunction continued to rise, with increases of 64 percent and 35 percent, respectively.

The researchers also conducted a subgroup analysis of the risk of digestive diseases among individuals with a single infection and those with a reinfection of COVID-19. The results revealed that, compared to the noninfected population, the group with reinfections had about a 440 percent increased risk of pancreatic diseases, while the group with a single infection faced a 44 percent increased risk.

The study also found that even in mild cases without hospitalization, the risks of gastrointestinal dysfunction, peptic ulcer disease, GERD, and nonalcoholic fatty liver disease were evident.

Even Those Who Had Mild Cases Are at Risk

The study emphasized that mild infections constitute over 95 percent of COVID-19 cases. While individuals with mild symptoms face a lower risk of digestive diseases than those with severe symptoms, the sheer number of infected individuals means that even a slight increase in the incidence rate of digestive diseases can lead to a significant rise in overall cases. This underscores the importance of preparedness in the health care system to handle the potential increase in cases.

The mechanisms underlying the association between COVID-19 infection and digestive diseases are not fully understood. However, the study proposed several possibilities, one of which is that the virus may be transmitted through the fecal-oral route, leading to digestive tract infections. Following the acute phase, this often leads to the development of irritable bowel syndrome (IBS), resulting in long-term functional gastrointestinal disorders.

Furthermore, the interaction between the spike protein of the COVID-19 virus and the angiotensin-converting enzyme 2 (ACE2) receptors in the digestive tract may also be associated with the progression of digestive diseases in COVID-19 patients. ACE2 plays a crucial role in the process of viral infection, and the epithelium of the digestive tract has a higher concentration of ACE2 than that in the lungs, making it more susceptible to COVID-19 infection. ACE2 is also present in the biliary tract and pancreas, which could contribute to the increased likelihood of gallbladder and pancreatic diseases following COVID-19 infection.

Another recent study, based on a cohort of over 11.4 million individuals from the National Healthcare Database of the U.S. Department of Veterans Affairs, found that patients hospitalized due to COVID-19 face an increased risk of gastrointestinal diseases. Notably, the risk was higher compared to patients hospitalized for seasonal influenza. The study was published in Nature Communications in March 2023.

The study indicated that individuals, one month after being infected with COVID-19, experienced an increased risk of GERD by 35 percent, peptic ulcer disease by 62 percent, acute pancreatitis by 46 percent, functional dyspepsia by 36 percent, acute gastritis by 47 percent, IBS by 54 percent, and cholangitis (inflammation of the bile duct) by 102 percent.

Regarding specific gastrointestinal symptoms, there was a 60 percent increased risk of constipation, a 44 percent increased risk of abdominal pain, a 58 percent increased risk of diarrhea, a 52 percent increased risk of vomiting, and a 46 percent increased risk of bloating.

Alleviating Long COVID With Gut Microbiome Formula

To alleviate the digestive system sequelae induced by COVID-19, researchers involved in a new study developed a gut microbiome formula. By addressing imbalances in the gut microbiome, this formula effectively mitigates the lingering symptoms in various systems and organs of COVID-19 patients. The clinical trial was published in The Lancet Infectious Diseases in December 2023.

The research team discovered that patients with long COVID exhibit a highly distinctive imbalance in their gut microbiome, which is likely a major contributing factor to the lingering effects of COVID-19.

Four hundred and sixty-three long-COVID patients were randomly assigned into two groups: One group received a probiotic formula, SIM01, and the other received vitamin C as a placebo for six months.

The probiotic formula is a micro-encapsulated lyophilized powder containing three strains of beneficial bacteria: Bifidobacterium adolescentis, Bifidobacterium bifidum, and Bifidobacterium longum. It also includes prebiotics that promote the growth of probiotics, such as galacto-oligosaccharides, xylo-oligosaccharides, and resistant dextrin.

The results indicated a significant improvement in long-COVID symptoms among patients in the probiotic formula group, including fatigue, memory loss, difficulty concentrating, gastrointestinal upset, and general unwellness. Moreover, compared to the placebo group, the probiotic formula group showed a greater improvement in symptoms such as joint pain, inability to exercise, shortness of breath, insomnia, muscle pain, coughing, hair loss, chest pain, and mood disturbance, although not particularly significant.

In addition to clinical symptom assessments, the research team analyzed the gut microbiome after six months of probiotic intake. They discovered that, compared to both the pre-intervention state and the placebo group, the probiotic formula group showed a significant increase in the abundance and diversity of beneficial gut bacteria, alongside a reduction in harmful bacteria. This highlights the effectiveness of the probiotic formula in regulating the gut microbiome.

Dr. Francis K.L. Chan, a study author and the dean of medicine and director of the Centre for Gut Microbiota Research at the Chinese University of Hong Kong, stressed that maintaining a balanced gut microbiome is crucial in preventing infectious diseases and their associated sequelae. He urged the public to recognize the importance of gut microbiome health as a means to reduce the risk of infections and the occurrence of postinfection symptoms.