COVID-19 Update From Ryan Ungaro, MD

Most patients with inflammatory bowel disease do not appear to be at increased risk of contracting COVID-19 but corticosteroids are "bad actors" that do raise the risk of severe disease, Ryan Ungaro, MD, told the virtual regional meeting of Advances in Inflammatory Bowel Disease.

Dr Ungaro is an assistant professor at the Icahn School of Medicine at Mount Sinai in New York, and has been involved in developing the SECURE-IBD database.

Risks for patients with IBD are primarily driven by older age, comorbidities, disease activity, and steroid use, he said. A systematic review demonstrated a relatively low incidence of COVID-19 in IBD patients, comparable to the general population, while a national VA database study revealed that out of “38,378 patients with IBD and 67,433 patients without IBD, 87 (0.23%) and 132 (0.20%) patients developed incident SARS-CoV-2 infection, respectively (p = 0.29).”

Patients with IBD who do become infected with the SARS-CoV2-19 virus “should be managed on a case-by-case basis,” Dr Ungaro said. A U.S. National Database Study comprising 40 million patients showed that patients with IBD who contract COVID-19 are not at increased risk of severe disease or death. Other studies have demonstrated that immune-mediated inflammatory disease (IMID), including IBD, “is not an independent risk factor for severe COVID-19 among hospitalized patients.”

A multivariable analysis of age the SECURE-IBD registry shows that mortality among patients with IBD hospitalized with COVID-19 is associated with ICU admission, requiring mechanical ventilation, and age of more than 60 years. Patients with 3 comorbidities are at highest risk, while patients with moderately to severely active disease are at a somewhat higher risk of severe COVID-19.

In the Mount Sinai health system of 5 hospitals, a retrospective cohort study with polymerase chain reaction (PCR)–confirmed COVID-19 infection, 6,792 patients with least 1 IMID and confirmed COVID-19 were not found to be at high risk of severe COVID-19, defined as requiring ventilation or death.

“Corticosteroids are bad actors in COVID-19 as they are in pretty much every infection,” Dr Ungaro said. A SECURE-IBD multivariable analysis and a study from Italy both showed that steroids appear to be consistently associated with increased risk of severe COVID-19 among patients with IBD and other immune-mediated diseases.

However, anti-tumor necrosis factor agents (TNFs) are low-risk and should be used as indicated. Dr Ungaro noted that a SECURE-IBD registry multivariable analysis of initial 525 cases showed no increased risk of severe COVID-19; in fact, anti-TNFs may have a protective effect against the virus. Subsequent analysis of more than 1,400 cases in an Italian cohort had similar results. In addition, a Global Rheumatology Alliance database analysis found that any anti-TNF use was associated with decreased risk of hospitalization.

However, some signals gleaned from the SECURE-IBD registry are indicating that thiopurine monotherapy and combination therapy with thiopurines and anti-TNFs may increase risk, Dr Ungaro noted. “This provides another reason to de-escalate combination therapy and taper steroids.”

Both anti-integrins and anti-IL-12/23 agents have proved similar to anti-TNF monotherapy in not increasing the risk of contracting COVID-19, Dr Ungaro stated. Nor is mesalamine associated with an increased risk of severe COVID-19, hospitalization, or death, despite early concerns about this agent. An early study that indicated a possible association with severe disease may have included a reporting bias, Dr Ungaro said.

New gastrointestinal symptoms are not uncommon among patients with IBD who contract COVID-19, he reported. According to data from SECURE-IBD, out of 2,917 patients who had both IBD and COVID-19, 764 (26.2%) experienced new GI symptoms. The most common symptoms were diarrhea and abdominal pain; these were more common among patients with active disease than among patients in remission.

However, a longitudinal study conducted at Cornell University that compared patients with IBD pre- and post- COVID-19 infection saw no significant impact during 6 months of follow-up on disease activity, inflammatory markers, IBD-related surgery, or hospitalization, Dr Ungaro said, suggesting that these patients do not suffer extended flares of IBD.

“Of course, the hot topic right now is vaccines among patients with IBD,” he continued. “We should definitely encourage our patients to get the COVID-19 vaccine.” There is no evidence that the vaccine increases the risk of an IBD flare. Although some immunosuppressive therapies — in particular prednisone may blunt antibody response, most patients with IBD on biologic therapies appear to mount adequate response to the vaccine.

Dr Ungaro cited a cited in which 14 health care workers without IBD and 49 patients with IBD received both doses of a mRNA vaccine. The patients with IBD were being treated with anti-TNF, anti-integrin, or anti-IL-12/23 therapies. “All 26 IBD patients who completed the 2 vaccine doses had positive antibodies,” he stated, “of whom 22 of 26 (84.6%) achieved levels that would qualify for convalescent plasma donation.”

The CLARITY Study of anti-SARS-CoV-2 spike antibody concentration stratified by biologic therapy (either infliximab or vedolizumab), prior infection, number of doses, and vaccine type among patients with IBD found that “the vast majority of patients seroconvert after 2 doses of COVID-19 vaccine.” Patients on combination therapy had somewhat lower antibody titers, Dr Ungaro pointed out.

The COVaRiPAD Study was a prospective assessment of mRNA-based vaccines among patients with IBD and rheumatoid arthritis, he explained. Patients taking prednisone showed “significant lower levels of vaccine antibodies” while B-cell therapy patients had very little response. “Of course, all of this hinges on the assumption that antibody titers are a good correlate for resistance to infection,” Dr Ungaro said, which while likely is absolutely established.

The recent recommendation by the Advisory Committee on Vaccine Practice (ACIP) that immunosuppressed patients receive a third dose of an mRNA vaccine has created questions among patients and physicians. Dr Ungaro pointed that the language of the recommendation states that patients taking high-dose corticosteroids, TNF blockers and “other biologic agents that are immunosuppressive or immunomodulatory” should receive a third dose.

“This is something that we’re going to be talking to our patients about; most of our patients are going to qualify for a third dose,” Dr Ungaro said.

--Rebecca Mashaw

Ungaro, R. Update on COVID-19 and inflammatory bowel disease. Presented at: Advances in Inflammatory Bowel Diseases regional meeting. September 11, 2021. Virtual.