麻豆传媒

Children with inflammatory bowel disease (IBD) who develop COVID-19 generally fare quite well with the infection, having low rates of hospitalization and little mortality. That was the encouraging message from a new analysis of data from an international registry that currently includes 4,578 cases, according to Michael Kappelman, MD, of the University of North Carolina at Chapel Hill.

Of the total cases of patients with IBD and COVID-19 reported to the , only 29 were in children under age 10. Of these, two (7%) were hospitalized (most often from the complication of multisystem inflammatory syndrome) and none died.

In contrast, as he reported at the virtual Crohn's and Colitis Congress, among the 157 patients ages 70 to 79, 46% were hospitalized and 11% died, and for the 108 who were age 80 and older, 50% were hospitalized and 20% died.

The Registry

"As we all know and as defined by the CDC, risk factors for severe COVID-19 infection include age and underlying medical conditions, particularly if not well controlled, as well as the use of immune-weakening medications such as corticosteroids," Kappelman said.

However, little has been known about the effects on COVID-19 among patients with IBD, and questions have arisen such as which patients are at risk for more severe COVID outcomes, whether there are difficulties in recognizing the infection in IBD patients, and what might be the effects of IBD medications.

"To begin to address many of these questions, our team at the University of North Carolina and colleagues at Mount Sinai in New York put together the SECURE-IBD database, with the main purpose of rapidly defining the impact of COVID-19 on patients with IBD, identifying risk factors, and characterizing outcomes," he said.

International participation in the registry, officially known as the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease, has been robust, he said, with cases reported from 65 countries and 50 U.S. states and territories. Cases began being reported in the beginning of March 2020, and from the late fall to early winter the overall rate of increase in cases was "quite alarming," Kappelman said.

The majority of cases have been from the U.S. and Western Europe, with some from Russia and growing numbers from South America, he noted.

The mean age of reported cases is 40, 50% are female, 57% have Crohn's disease, and 17% were hospitalized with a mean length of stay of 9 days. A total of 3% required intensive care and the overall death rate was 2%.

The data in this registry are similar to what has been observed in other cohorts. For instance, in that included 79 patients with established IBD, risk factors for COVID-19 mortality included age over 65, having active disease, and having higher scores on the Charlson comorbidity index.

"Just as in the general population, comorbidities also really matter," Kappelman commented.

Effects of Medication?

He and his colleagues also have focused on the impact of medications on the course of COVID-19. In that included 525 cases, risk factors for severe COVID-19 included older age (OR 1.04, 95% CI 1.01-1.02); having two or more comorbidities (OR 2.9, 95% CI 1.1-7.8); use of sulfasalazine or 5-aminosalicylate (OR 3.1, 95% CI 1.3-7.7); and especially, treatment with systemic corticosteroids, where the adjusted odds ratio almost reached 7 (OR 6.9, 95% CI 2.3-20.5).

Similar risks for steroids were seen in the Italian study, where the use of these medications was associated with an odds ratio of 4.94 (95% CI 0.95-25.55, P=0.05).

In contrast, no increased risks were seen for the use of tumor necrosis factor (TNF) inhibitors. In SECURE-IBD, there was no significant increase in risk for severe COVID-19 among patients treated with TNF inhibitors (OR 0.9, 95% CI 0.4-2.2).

Similar findings were seen in of 24 studies that found lower relative risks with biologic treatment in IBD patients for hospitalization (RR 0.34, 95% CI 0.19-0.61) and mortality (RR 0.22, 95% CI 0.13-0.38).

"Moreover, emerging data from the Global Rheumatology Alliance found no increased risk among rheumatic disease patients receiving anti-TNF therapy, and there was potentially even a protective effect," Kappelman said.

An additional question with regard to COVID-19 in patients with IBD has been how to recognize the infection.

"There is emerging literature that indicates that these patients not only have fever, cough, and dyspnea, but also have a number of gastrointestinal symptoms including diarrhea, nausea, abdominal pain, and vomiting. So be on high alert for IBD patients developing new GI symptoms and think about COVID. Is COVID-19 the new C. diff?" he said, referring to the increased risk and worse outcomes among IBD patients who develop Clostridium difficile infection.

The Vaccine

A final concern is the use of COVID-19 vaccines among IBD patients. Patients with immunosuppression -- including most IBD patients -- were excluded from the Pfizer and Moderna vaccine trials, so the effectiveness of the vaccine in these patients is largely unknown. The literature indicates that most other vaccines have been effective in IBD patients, or perhaps slightly less so than in the general population.

The durability of the response is not known, as is whether additional boosters will be needed.

The safety of the vaccine also is unclear, but "it's probably reasonably safe," Kappelman said. "There's no clear rationale for a different safety profile in IBD patients and no clear rationale for how vaccination might alter the course of IBD, so it's very likely that the benefits of immunization far outweigh the risks," he concluded.

A limitation of the SECURE-IBD analyses, he said, is that they are based on a convenience sample and there may be reporting bias.

Comment