Inflamm Bowel Dis. 2021 Sep 16;izab207. doi: 10.1093/ibd/izab207. Online ahead of print.

Joelynn Dailey ^1 2, Lina Kozhaya ³, Mikail Dogan ³, Dena Hopkins ^1 2, Blaine Lapin ^1 4, Katherine Herbst ^1 5, Michael Brimacombe ^1 5, Kristen Grandonico ^1 2, Fatih Karabacak ³, John Schreiber ^1 6, Bruce Tsan-Liang Liang ⁷, Juan C Salazar ^1 6, Derya Unutmaz ³, Jeffrey S Hyams ^1 2

Author information

• ¹Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA.
• ²Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, CT, USA.
• ³Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
• ⁴Division of Rheumatology, Connecticut Children's Medical Center, Hartford, CT, USA.
• ⁵Division of Research, Connecticut Children's Medical Center, Hartford, CT, USA.
• ⁶Division of Pediatric Infectious Diseases and Immunology, Connecticut Children's Medical Center, Hartford, CT, USA.
• ⁷Pat and Jim Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, USA.

Abstract

Background: Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial.

Methods: We performed a prospective longitudinal cohort study evaluating SARS-CoV-2 spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines. The IgG antibody to the spike protein binding domain of SARS-CoV-2 was assayed with a fluorescent bead-based immunoassay that takes advantage of the high dynamic range of fluorescent molecules using flow cytometry. A sensitive and high-throughput neutralization assay that incorporates SARS-CoV-2 spike protein onto a lentivirus and measures pseudoviral entry into ACE2-angiotensin converting enzyme 2 (ACE2) expressing human embryonic kidney 293 (HEK-293) cells was used.

Results: There were 436 patients enrolled (mean age, 17 years, range 2-26 years; 58% male; 71% Crohn's disease, 29% ulcerative colitis, IBD-unspecified). Forty-four (10%) of enrolled subjects had SARS-CoV-2 S-RBD IgG antibodies. Compared to non-IBD adults (ambulatory) and hospitalized pediatric patients with PCR documented SARS-CoV-2 infection, S-RBD IgG antibody levels were significantly lower in the IBD cohort and by 6 months post infection most patients lacked neutralizing antibody. Following vaccination (n = 33), patients had a 15-fold higher S-RBD antibody response in comparison with natural infection, and all developed neutralizing antibodies to both wild type and variant SARS-CoV-2.

Conclusions: The lower and less durable SARS-CoV-2 S-RBD IgG response to natural infection in IBD patients receiving biologics puts them at risk of reinfection. The robust response to immunization is likely protective.