Stomach pain, constipation, diarrhea, vomiting, bloating — these are symptoms frequently reported by people with long COVID.
Now a large new study reports that COVID patients were significantly more likely to experience gastrointestinal problems a year after infection than people who were not infected.
The study, published Tuesday in the journal Nature Communications, compared medical records of 154,068 COVID patients in the Veterans Health Administration system with about 5.6 million patients of similar age and other characteristics who had not contracted the coronavirus. COVID patients were 36% more likely to have long-term gastrointestinal problems that they did not have before their infection, with 9,605 of them experiencing issues affecting the digestive system, intestines, pancreas or liver.
The most common diagnoses were acid-related disorders, such as gastroesophageal reflux disease (known as GERD) and peptic ulcer disease, which were identified in more than 2,600 patients.
"There seems to be some dysregulation that points to a major imbalance in acid production," said the senior author of the study, Dr. Ziyad Al-Aly, chief of research and development at the VA St. Louis Health Care System and a clinical public health researcher at Washington University in St. Louis.
Serious inflammatory illnesses — such as acute pancreatitis and cholangitis, which is inflammation of the bile duct system — affected a much smaller percentage of patients, but they were nonetheless more common among those who had COVID than those who did not.
"With all of these disorders, there is an increased odds ratio, meaning that the people who had COVID and survived for 30 days or longer were more at risk of each of these categories," said Dr. Saurabh Mehandru, a professor of gastroenterology at the Icahn School of Medicine at Mount Sinai in New York who was not involved in the study.
Long COVID patients were also at higher risk of gastrointestinal symptoms, the most common being constipation, abdominal pain and diarrhea.
The study, like others drawing on the database of veterans, involves a patient population that is largely white and male with an average age of about 61. Still, the same patterns were seen among the study's 37,000 post-COVID Black patients and nearly 17,000 post-COVID female patients, Al-Aly said.
The patients became infected during the pandemic's early waves, testing positive for the coronavirus between March 1, 2020, and Jan. 15, 2021, the overwhelming majority before vaccines were available. Al-Aly and Mehandru noted that the experience might be different for people infected more recently. Newer virus variants might have different effects, they said, and some research suggests that vaccines can reduce the risk of various long COVID symptoms.
There are several reasons coronavirus infections may fuel long-term gastrointestinal problems. Mehandru, who has studied some possible causes, said his team and others had found that a protein the virus attaches to on some cell surfaces, called the ACE2 receptor, was abundant in the lining of the small intestine. Those receptors might provide a way for the virus to directly enter the digestive system, he said. It's also possible that some viral fragments remained after infections resolved, keeping patients' immune systems activated and generating inflammation-related symptoms.
Another possibility is the "gut-brain connection," said Mehandru, explaining that "when we're stressed, we have intestinal manifestations." And, he added, "some of the symptoms could also be because of a generalized state of being unwell or having illness outside of the intestines, which could impact how we move our bowels or mean that we feel bloated or have acid reflux."
Al-Aly said most long COVID patients had other symptoms besides gastrointestinal problems, suggesting that the condition was "too complex to have just one mechanism that explains all of it."
The new study did not identify whether certain previous health conditions, such as diabetes or cardiovascular disease, put people at greater risk of post-COVID gastrointestinal problems. Like many other long COVID studies, it did find that people whose initial infections were severe enough to warrant intensive care or other hospitalization were more prone to long-term symptoms. Still, people with mild initial infections — who make up a majority of COVID patients — were nonetheless at greater risk than people who were not infected.
Underscoring the significance of post-COVID symptoms, the study found that long COVID patients were at greater risk of gastrointestinal problems than nearly 6 million people in the veterans database before the pandemic. It also found that people hospitalized with a coronavirus infection were more likely to develop long-term gastrointestinal issues than people hospitalized with the flu.
Al-Aly did sound one note of optimism. While some symptoms of long COVID, such as fatigue and brain fog, can be intractable for months despite different therapies, many gastrointestinal symptoms are treatable.
"Obviously, there's no one treatment for all of this," he said. "But I think these are diagnoses and signs and symptoms that could be managed."