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.

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. 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 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.

Objectives: Despite limited data, methotrexate (MTX) is often used as primary maintenance therapy in pediatric Crohn disease (CD). We sought to assess the effectiveness of MTX as "initial" primary maintenance therapy in newly diagnosed mild/moderate pediatric CD and ascertain baseline predictive factors. Methods: Single-center 10-year retrospective review of newly diagnosed CD patients treated with MTX as primary maintenance therapy. We compared baseline characteristics of those patients with sustained response/clinical remission to those patients who escalated to anti-TNF therapy within 1 year. Pediatric Crohn Disease Activity Index (PCDAI) ≤ 10 defined remission. Results: We identified 65 patients (mean age, 11.8 years; 72 % male; mean ± SD PCDAI, 17.8 ± 10.5) who started MTX ≤4 months of diagnosis as their primary maintenance therapy. Initial therapy prior to MTX was corticosteroids (CS) (54/65), defined diet (4/65), and combination CS/diet (6/65). Oral dosing was used in 55%; mean dose was 11.4 mg/m 2 orally and 12.5 mg/m 2 subcutaneously. At 1 year, 36 of 65 (55%) were on MTX monotherapy, and of those, 32 of 36 were in clinical remission; 81% were in steroid-free remission for the year following induction. For the 36 patients on MTX at 1 year, 14 (39%) had gross mucosal healing (22% of the original cohort). Ten additional patients had mucosal improvement (37% of total healed/improved). Fifteen patients (23%) were early failures, transitioning to anti-TNF ≤4 months. Baseline PCDAI, hemoglobin, ESR, albumin, and route of administration were not predictive of outcome. MTX was well tolerated in our cohort, with only 1 patient stopping due to elevated aminotransferases. No patient required CD surgery in the 1-year follow-up. Conclusions: MTX may have a primary maintenance role in mild/moderate CD.