Survivors of COVID are at increased risk of long-term gastrointestinal disease

Surviving a bout of COVID-19 can significantly increase the risk of developing a range of long-term gastrointestinal symptoms and conditions—from constipation and diarrhea to chronic acid reflux, pancreatitis, and inflammation of the bile ducts—according to a study published this week in Nature Communications.

The study likely confirms what many COVID-19 patients already know all too well. But the analysis is among the largest and most comprehensive to assess the boost in relative and absolute risks, drawing on medical records from more than 11,652,484 people in Department of Veterans Affairs databases.

The study was led by clinical epidemiologist Ziyad Al-Aly at the VA Saint Louis Health Care System in Saint Louis. With his colleagues, Al-Aly reviewed the medical records of more than 154,000 people who had COVID-19 between March 2020 and January 2021. The researchers then compared the rates of gastrointestinal problems among the COVID-19 survivors in the year after infection them with rates observed in two control cohorts. One was a contemporary cohort of over 5.6 million people who went from March 2020 to January 2021 without any evidence of COVID-19 infection. The other was 5.8 million people followed for a year before the pandemic, which served as a control for unreported cases of COVID-19 in the modern cohort.

The researchers found increased relative risks and absolute risk – in the form of excess disease burden per 1,000 people – for a number of predefined gastrointestinal conditions and symptoms. Compared to the control groups, the COVID-19 survivors had more constipation, diarrhea, abdominal pain, vomiting, and bloating in the year after infection.


Survivors also had a 35 percent higher risk than controls of developing GERD (gastroesophageal reflux disease), with 15.5 more cases per 1,000 of being overweight than controls. The risk of inflammation of the bile ducts (cholangitis) doubled, but was still rare, with an excess burden of just 0.22 cases. Survivors also had a 62 percent higher risk of peptic ulcer, with an excess burden of 1.57 cases, and a 54 percent higher risk of irritable bowel syndrome, with an excess burden of 0.44 cases. Overall, COVID survivors had a 37 percent higher risk of developing any gastrointestinal condition, with 17.37 cases of being overweight.

The researchers did not look at underlying health conditions that might be linked to these higher risks, but noted that the more severe a patient’s case of COVID, the higher the risk of long-term gastrointestinal problems. In other words, those in the ICU with COVID-19 had the greatest risks, followed by those who were hospitalized and then those who were not. That said, people who were not hospitalized were still at increased risk across the range of conditions assessed compared to controls.

As with other forms of long-term COVID, which can wreak havoc on many parts and systems of the body, it’s unclear how the viral infection leads to gastrointestinal problems in the year after infection. Researchers have hypothesized that a persistent virus may exist in certain selected areas of the body. There could also be a disruption in the gut microbiome, tissue injury, autoimmune mechanisms or chronic inflammation. Some immunological studies have suggested that people with long-term COVID may exhibit a dangerous combination of persistent immune responses to prolonged SARS-CoV-2 antigen, reactivation of herpes viruses (such as Epstein-Barr, which causes monochromia), and chronic inflammation. But for now, researchers don’t have a complete understanding of the condition.

It’s also unclear who is at risk of developing long-term problems after COVID-19. Although studies have shown that vaccination can reduce the risk of long-term COVID, it does not appear to completely eliminate the risk, nor does previous infection. And an individual’s risk may change over time since the last vaccination/infection and possibly with different SARS-CoV-2 variants. In the current study, the time frame of the examined COVID cases was largely before the widespread distribution of vaccines, making it impossible for researchers to assess the effects of vaccination on risks.

“Overall the evidence base reinforces the need for continued emphasis on primary prevention of SARS-CoV-2 infection (and prevention of reinfection) as the foundation of the public health response,” concluded Al-Aly and colleagues. “Taken together with the evidence gathered so far on the scale and scope of organ dysfunction in Long COVID, the findings of this report call for the urgent need to develop strategies to prevent and treat the post-acute consequences of SARS- CoV-2.”

Leave a Comment