Since the onset of the COVID-19 pandemic, researchers have struggled with how to gather data to determine whether patients with inflammatory bowel disease (IBD) are more susceptible to infection due to their underlying disease and therapeutic treatments, without unnecessarily increasing their risk of exposure through extra medical visits and procedures. Mount Sinai researcher Serre-Yu Wong, MD, PhD, believes she has found the answer.

“We have patients with IBD who are receiving regular treatments at the Mount Sinai Therapeutic Infusion Center, and we collect blood samples during those visits,” says Dr. Wong, Instructor of Medicine (Gastroenterology) at the Icahn School of Medicine at Mount Sinai. “Using antibodies as a surrogate for infection, we can explore the risk of infection among this population in a safe way. This is important because, while we have data on patients who became sick with COVID-19, we do not know how many patients got infected but were asymptomatic. This is because the patients who did not get sick are less likely to have been tested and, therefore, remain undetected.”

As it turned out, the same idea was being explored by researchers at the University of Oxford in England, leading Dr. Wong to partner with them. The result is the ICARUS-IBD International Study of COVID-19 Antibody Response Under Sustained Immune Suppression: a Global Seroprevalence Study of COVID-19 in IBD. The study will follow adult patients who are receiving infusion therapy (i.e., infliximab or vedolizumab) at IBD centers of excellence around the world to assess risk factors for infection and the impact of COVID-19 on their disease.
“Our goal is to identify the biological, social, and treatment-related factors that determine whether patients with IBD become infected with SARS-CoV-2, the virus that causes COVID-19,” Dr. Wong explains. “This will enable us to risk-stratify patients and provide them with informed advice that helps protect them from COVID-19 infection and mortality.”

Each of the 19 IBD centers participating in the study will enroll 500 patients and follow them for 48 weeks. Blood collection and a questionnaire to gather data on COVID-19-related symptoms, diagnosis, and potential social exposures, in addition to other health information such as current medications, will be conducted during each patient’s first visit and again every eight weeks over the course of the study. Patients will also undergo serological screening at week zero for baseline prevalence and again at weeks 24 and 48 to assess for seroconversions. Using this data, the research team will explore the seroprevalence of COVID-19 antibodies among participants, identify the clinical factors—such as medications, comorbidities, and social exposures—associated with seropositivity and asymptomatic disease, and characterize the circulating immune response to SARS-CoV-2.

“We are interested in the type, level, and durability of the antibodies produced, and whether the patients’ IBD or associated immunosuppressant therapy has any impact on those antibodies,” Dr. Wong says. “We will also be conducting cytokine profiling to see if there is any association with asymptomatic disease, looking for antibodies that were generated by a previous coronavirus to see if there is any cross-reactivity to COVID-19, and exploring whether T cell responses are playing a role in generating antibodies in a subset of participants.”

Preliminary study data and emerging literature on COVID-19 patients have also prompted Dr. Wong and her colleagues to look at the role of autoantibodies in IBD—something researchers have explored for years as potential biomarkers but that have had only limited predictive and diagnostic use. “There has been media coverage of a manuscript that suggests that some COVID-19 survivors have experienced an increase in autoantibody formation,” Dr. Wong says. “This is invaluable information as we learn more about COVID-19 and long-term symptoms. It raises the question as to whether this phenomenon could occur among IBD patients and what effect this has on their IBD course. Moreover, it raises some very basic immunological questions that researchers have been grappling with for years—can acute infectious diseases such as COVID-19 induce or have an impact on chronic autoimmune or auto-inflammatory diseases such as IBD, and, if so, how does the immune system go awry when it should be protecting us?”

Dr. Wong indicates that baseline data is being prepared for publication, and the goal is to publish full clinical data in late 2021. She expects the results will not only assist gastroenterologists in stratifying, treating, and protecting patients during this and future health care crises but could also provide insights on how patients may respond to a vaccine and how certain immunosuppressant agents interact with SARS-CoV-2 infection among patients with IBD. “We know the virus induces an immune system response—a cytokine storm—that causes collateral damage,” Dr. Wong says. “Could the medications that we administer patients prevent that phenomenon from happening? It is unclear yet if we will be able to answer that, but it is something we are looking into.”