Evidence suggests that immunogenicity to mRNA-based SARS-CoV-2 vaccination in immunosuppressed patients may be reduced. This study assessed the response to 2 doses of mRNA-based SARS-CoV-2 vaccine among 133 participants with underlying chronic inflammatory disease, many of whom were receiving glucocorticoids, B-cell depletion therapy, or other immunosuppressant therapy.

Background: Individuals with Chronic Inflammatory Diseases (CID) are frequently treated with immunosuppressive medications that can increase their risk of severe COVID-19. While novel mRNA-based SARS-CoV-2 vaccination platforms provide robust protection in immunocompetent individuals, the immunogenicity in CID patients on immunosuppression is not well established. Therefore, determining the potency of SARS-CoV-2 vaccines in the setting of immunosuppression is essential to risk-stratify CID patients with impaired protection and provide clinical guidance regarding medication management. Methods: We conducted a prospective assessment of mRNA-based vaccine immunogenicity in 133 adults with CIDs and 53 immunocompetent controls. Blood from participants over 18 years of age was collected before initial immunization and 1-2 weeks after the second immunization. Serum anti-SARS-CoV-2 spike (S) IgG+ binding, neutralizing antibody titers, and circulating S-specific plasmablasts were quantified to assess the magnitude and quality of the humoral response following vaccination. Results: Compared to immunocompetent controls, a three-fold reduction in anti-S IgG titers (P=0.009) and SARS-CoV-2 neutralization (p<0.0001) were observed in CID patients. B cell depletion and glucocorticoids exerted the strongest effect with a 36- and 10-fold reduction in humoral responses, respectively (p<0.0001). Janus kinase inhibitors and antimetabolites, including methotrexate, also blunted antibody titers in multivariate regression analysis (P<0.0001, P=0.0023, respectively). Other targeted therapies, such as TNF inhibitors, IL-12/23 inhibitors, and integrin inhibitors, had only modest impacts on antibody formation and neutralization. Conclusions: CID patients treated with immunosuppressive therapies exhibit impaired SARS-CoV-2 vaccine-induced immunity, with glucocorticoids and B cell depletion therapy more severely impeding optimal responses.

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Purpose of reviewMultiple new medications with novel mechanisms of action are now available to treat Crohn's disease (CD). However, they have varying effectiveness in the management of perianal CD. Identifying the most appropriate therapy and optimizing it is essential to maximize effectiveness of therapy. Additionally, the management of perianal CD requires imaging of the perianal area to identify the fistula anatomy and local complications such as abscesses that require surgical drainage. Initial surgical assessment is key to drain abscesses and allow fistula healing with medical therapy. Recent findingsAlthough anti-tumor necrosis factor (TNFs) remain the most effective medications to treat perianal CD, realworld data suggests that ustekinumab may be a 2 nd -line option in patients nonresponsive to an anti-TNF or having contraindications. Mesenchymal stem cells are an emerging therapeutic approach that is currently in Phase 3 trials in the United States and poised to play a major role in the treatment algorithm.

Background & Aims Intestinal fibrosis has recently been characterized in adult ulcerative colitis and may affect motility, diarrhea, and the symptom of urgency. We aimed to characterize the presence of fibrosis in pediatric patients with ulcerative colitis, and its link to severity and chronicity of mucosal inflammation, as well as clinical factors of severity. Methods We performed a single center cross-sectional study in ulcerative colitis children ages 1-18 years undergoing colectomy or proctocolectomy. Tissue cross-sections were derived from proximal, mid and distal colon and rectum, and inflammation and fibrosis were graded based on previously developed scores. Clinical data were collected prospectively. Results 205 intestinal sections of 62 patients were evaluated. Median age at diagnosis was 13 years, 100% had extensive colitis, and all resections were done for refractory disease. The presence, chronicity and degree of inflammation were linked with the presence of fibrosis. Thickness of the muscularis mucosa was also linked with presence and chronicity of inflammation. The overall submucosal fibrosis burden was associated with prior anti-tumor necrosis factor use. Conclusion Pediatric patients with ulcerative colitis exhibit colorectal submucosal fibrosis and muscularis mucosa thickening, which correlates with the presence, chronicity and degree of mucosal inflammation. Fibrosis should be recognized as a complication of pediatric ulcerative colitis, and ulcerative colitis should be considered a progressive disease.

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