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Clinical Context

Gastrointestinal (GI) symptoms have not been a hallmark of COVID-19, but a study by Marasco and colleagues suggests that GI symptoms might be more frequent in COVID-19 than previously thought. They prospectively evaluated 871 hospitalized patients with and without COVID-19 in their analysis, the results of which were published in the January 2022 issue of the American Journal of Gastroenterology.^[1]

A total of 59.7% of patients with COVID-19 had GI symptoms compared with 43.2% in the control group without COVID-19. Symptoms particularly associated with COVID-19 included nausea and loose stools with urgency. At 1 month after hospital admission, GI symptoms had generally subsided in the COVID-19 cohort, but nausea remained more prevalent compared with the control group. Variables associated with a higher rate of nausea at 30 days included female sex, high body mass index, the presence of dyspnea, and elevated C-reactive protein.

This study found that GI symptoms were common in COVID-19, but do they affect prognosis of the infection? The current study analyzes this possibility.

Study Synopsis and Perspective

Patients with COVID-19 who experience GI symptoms have overall worse in-hospital complications but less cardiomyopathy and mortality, according to a new study.

About 20% of COVID-19 patients experience GI symptoms, such as abdominal pain, diarrhea, nausea, and vomiting, which clinicians should consider when treating their hospitalized patients, write researchers led by Nikita Patil, MD, a hospitalist at Nash General Hospital–UNC Nash Healthcare in Rocky Mount, North Carolina, in Gastro Hep Advances.^[2]

"It's important to know that certain complications are higher in people with GI symptoms," she said in an interview. "Even without an increased risk of death, there are many problems that affect quality of life and lead to people not being able to do the things they were able to do before."

Dr Patil and colleagues analyzed the association of GI symptoms with adverse outcomes in 100,902 patients from the Cerner Real-World Data COVID-19 Database, which included hospital encounters and emergency department visits for COVID-19 between December 2019 and November 2020; the data were taken from electronic medical records at centers with which Cerner has a data use agreement. The researchers also looked at factors associated with poor outcomes, such as acute respiratory distress syndrome, sepsis, and ventilator requirement or oxygen dependence.

The average age of the patients was 52 years, and a higher proportion of patients with GI symptoms were aged 50 years and older. Of those with GI symptoms, 54.5% were women. Overall, patients with GI symptoms were more likely to have higher Charlson Comorbidity Index scores and have comorbidities such as acute liver failure, gastroesophageal reflux disease, GI malignancy, and inflammatory bowel disease.

The research team found that patients with COVID-19 with GI symptoms were more likely to have acute respiratory distress syndrome (odds ratio, 1.20; 95% CI, 1.11-1.29), sepsis (OR, 1.19; 95% CI, 1.14-1.24), acute kidney injury (OR, 1.30; 95% CI, 1.24-1.36), venous thromboembolism (OR, 1.36; 95% CI, 1.22-1.52), and GI bleeding (OR 1.62; 95% CI, 1.47-1.79) compared with patients with COVID-19 without GI symptoms (P<.0001 for all comparisons). At the same time, those with GI symptoms were less likely to experience cardiomyopathy (OR, 0.87; 95% CI, 0.77-0.99; P=.027), respiratory failure (OR, 1.20; 95% CI, 1.11-1.29; P<.0001), or death (OR, 0.71; 95% CI, 0.67-0.75; P<.0001).

GI bleed was the most common GI complication, found among 2% of all patients, and was more likely in patients with GI symptoms than in those without (3.5% vs. 1.6%). Intestinal ischemia, pancreatitis, acute liver injury, and intestinal pseudo-obstruction were not associated with GI symptoms.

Among the 19,915 patients with GI symptoms, older age, higher Charlson Comorbidity Index scores, use of proton pump inhibitors, and use of H₂ receptor antagonists were associated with higher mortality, acute respiratory distress syndrome, sepsis, and ventilator or oxygen requirement. Men with GI symptoms also had a higher risk for mortality, acute respiratory distress syndrome, and sepsis.

In particular, proton pump inhibitor use was associated with more than twice the risk for acute respiratory distress syndrome (OR, 2.19; 95% CI, 1.91-2.50; P<.0001). Similarly, H₂ receptor antagonist use was associated with higher likelihood of death (OR, 1.78; 95% CI, 1.57-2.02), as well as more than 3 times the risk for acute respiratory distress syndrome (OR, 3.75; 95% CI, 3.29-4.28), more than twice the risk for sepsis (OR, 2.50; 95% CI, 2.28-2.73), and nearly twice the risk for ventilator or oxygen dependence (OR, 1.97; 95% CI, 1.68-2.30) (P<.0001 for all).

The findings could guide risk stratification, prognosis, and treatment decisions in patients with COVID-19 with GI symptoms, as well as inform future research focused on risk mitigation and improvement of COVID-19 outcomes, Dr Patil said.

"The protocols for COVID-19 treatment have changed over the past 2 years with blood thinners and steroids," she said. "Although we likely can't avoid antireflux medicines entirely, it's something we need to be cognizant of and look out for in our hospitalized patients."

One study limitation was its inclusion of only inpatient or ED encounters and, therefore, omission of those treated at home; this confers bias toward those with more aggressive disease, according to the authors.

The authors reported no grant support or funding sources for this study. One author declared grant support and consultant fees from several companies, including some medical and pharmaceutical companies, which were unrelated to this research. Dr Patil has disclosed no relevant financial relationships.

Gastro Hep Adv. Published online August 26, 2022.

Clinical Implications

• In a previous study, 59.7% of hospitalized patients with COVID-19 had GI symptoms compared with 43.2% in the control group without COVID-19. The most salient GI symptom at admission and 1 month later was nausea.
• The current study finds that GI symptoms among patients hospitalized for COVID-19 are associated with multiple complications, such as acute respiratory distress syndrome and sepsis, but they were not associated with a higher risk for mortality.

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