Since the beginning of the COVID-19 pandemic, Walter W. Chan, MD, MPH, director of the Center for Gastrointestinal Motility at Brigham and Women’s Hospital, and colleagues in the Division of Gastroenterology, Hepatology and Endoscopy, have led several clinical studies investigating COVID-19 infection presentation, risk factors and outcomes on the gastrointestinal (GI) system.

In April 2020, at the height of first U.S. wave of the pandemic, Dr. Chan and a team of investigators published a study in Gastroenterology that examined 318 patients with confirmed COVID-19 infection at Massachusetts hospitals, including the Brigham. The study confirmed what was still considered unclear at the time — that GI symptoms were, in fact, an important presentation of COVID-19. The study found that about 60 percent of patients with COVID-19 reported at least one GI symptom, including diarrhea (33.7 percent), nausea (26.4 percent) and loss of appetite (34.8 percent). The study also revealed that GI symptoms were the initial symptoms in 14.2 percent of individuals and were the predominant complaint in 20.3 percent of patients.

“This Brigham study was one of the first in the U.S. to explore the manifestations of COVID-19 on the digestive system,” said Dr. Chan. “It demonstrated that COVID-19 affects the GI system in ways that weren’t completely established at the time. Our findings may have helped clinicians identify COVID-19 sooner, especially for those patients whose symptoms are predominantly gastrointestinal.”

Multidisciplinary Team Conducts GI-Related COVID-19 Research

The research study began in March of 2020 after Walker D. Redd, MD, an internal medicine resident at the Brigham, observed that many hospitalized COVID-19 patients reported prominent GI symptoms, such as diarrhea, nausea, vomiting and lack of appetite that may sometimes lead to prolonged hospitalizations. At the time, the only data related to possible COVID-associated GI symptoms came from China and the Centers for Disease Control and Prevention (CDC) hadn’t yet listed GI symptoms as part of COVID-19’s clinical presentation.

To conduct this research and other studies, a multidisciplinary team at the Brigham extracted, collected and analyzed patient data. The team was led by Drs. Chan, Redd and Lin Shen, MD, MBI, the division director of medical informatics at the Brigham, and included several other division colleagues and trainees.

“Our outstanding clinical research team was uniquely positioned to conduct these COVID-related studies in a rapid fashion as the pandemic was emerging,” said Dr. Chan. “We have a strong group of faculty and trainees who are highly experienced in conducting clinical research, using the newest technology and medical informatic tools to help us identify patients and extract large datasets in order to perform detailed analyses.”

The Impact of Underlying GI Conditions on COVID-19

Throughout the pandemic, Dr. Chan and his colleagues also conducted several clinical research studies on the impact of COVID-19 on certain underlying GI conditions.

In a study published in Liver International, the team examined the impact of underlying chronic liver disease, including cirrhosis and non-alcoholic fatty liver disease, on COVID-19 illness. The study found that COVID-19 patients with chronic liver disease had more negative outcomes and were at a higher risk of having severe COVID-19 than patients without liver disease.

“Our study found that COVID-19 patients with liver disease were at a higher risk of needing advanced care, such as ICU admission, mechanical ventilation and death,” said Dr. Chan. “In particular, those with non-alcoholic fatty liver disease were among the highest risk.”

In other research, the Brigham investigators evaluated the potential impact of COVID-19 on the pancreas. Due to early reports indicating that a substantial proportion of COVID-19 patients might develop pancreatitis, as assessed by elevated serum lipase levels, the team conducted a study that examined the significance of abnormal pancreatic enzymes among hospitalized patients with COVID-19.

Their retrospective cohort study, published in The American Journal of Gastroenterology, showed that among 71 hospitalized COVID-19 patients, 12 percent developed hyperlipasemia, with only 3 percent over three times more than normal. Acute pancreatitis, as defined by established criteria, wasn’t observed in this cohort of hospitalized patients. As such, Dr. Chan cautions providers not to rely on lab values alone to diagnose these patients.

Examining the Impact of GI Conditions on COVID-19

During the pandemic, Dr. Chan and his team have also studied the impact of other GI conditions on the severity of COVID-19 and outcomes. These include:

• Inflammatory bowel disease (IBD) and COVID-19: The team and collaborators from Massachusetts General Hospital evaluated the risk of a COVID-19 infection among patients with IBD being treated with systematic immunosuppressive therapy. The cohort study, which was published in Inflammatory Bowel Diseases, confirmed that less than 1 percent of 5,000 patients with IBD developed COVID-19. Moreover, no significant differences were noted between those treated with systematic immunosuppressive therapy and ones who were not. Immunosuppressive therapy wasn’t associated with more severe COVID-19 infection.
• COVID-19 and cancer: In a study published in The Journal of Clinical Gastroenterology, Brigham researchers assessed the GI manifestations of COVID-19 among patients with active malignancy. Among cancer patients who were hospitalized with COVID-19, 63 percent had at least one new gastrointestinal symptom, with diarrhea, vomiting and anorexia being the most common; 17 percent had severe symptoms. In addition, 33 percent of cancer patients with COVID-19 had elevated liver enzymes at the time of presentation, and patients with raised liver enzymes were more likely to experience GI symptoms.
• Proton pump inhibitors (PPIs) and COVID-19: Dr. Chan and his team evaluated the potential relationship between PPI exposure and clinical outcomes of hospitalized COVID-19 patients. The study, which was presented at the American College of Gastroenterology (ACG) Annual Meeting and is forthcoming in the journal BMJ Open, showed that PPI use among hospitalized COVID-19 patients was associated with a greater need for mechanical ventilation and increased in-hospital mortality. The study authors note that further research is needed to understand if these findings represent a causal relationship or whether an underlying confounding condition like GERD drove these outcomes.
• Clostridioides difficile infection (CDI) in COVID-19 patients: In a study presented at the ACG Annual Meeting and forthcoming in the journal JGH Open, Brigham investigators assessed the prevalence and outcome of CDI infection among hospitalized COVID-19 patients. Despite high antibiotics use, COVID-19 patients didn’t have a higher CDI-positive rate compared to historic controls pre-pandemic. However, among hospitalized COVID-19 patients who developed CDI, the in-hospital mortality was significantly increased.

Further Research on COVID-19 and the GI System

The Brigham research team is building on their strong research foundation and conducting follow-up studies on the GI manifestations of COVID-19. Like other clinical and basic researchers at the Brigham, Dr. Chan and his colleagues are also exploring the potential long-term health complications of  COVID-19 infection on the GI system. There is still much to learn about the short and long-term effects of COVID-19 and the Brigham is positioned to be at the forefront of discovery.