Antibody Responses to SARS-CoV-2 after Infection or Vaccination in Children and Young Adults with Inflammatory Bowel Disease.

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: W e 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. 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 expressing HEK-293 cells was used.

RESULTS: 436 patients were enrolled (mean age 17 years, range 2-26 years, 58% male, 71% Crohn’s disease, 29% ulcerative colitis, IBD-unspecified). 44 (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 to natural infection, and all developed neutralizing antibodies to both wild type and variant SARS-CoV-2.

CONCLUSIONS AND RELEVANCE: 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.

SUMMARY: Our study showed a low and poorly durable SARS-CoV-2 S-RBD neutralizing IgG response to natural infection in IBD patients receiving biologics potentially putting them at risk of reinfection. However, they also had a robust response to immunization that is likely protective.