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Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Summary: Background: Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Methods: Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. Findings: Forty-three infliximab-treated patients with IBD were recruited (30 Crohn's disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.037). Bilophila abundance was associated with better serological response, while Streptococcus was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R2X 0.25, R2Y 0.26, Q2 0.15; CV-ANOVA p = 0.038). Trimethylamine, isobutyrate and omega-muricholic acid were associated with better response, while succinate, phenylalanine, taurolithocholate and taurodeoxycholate were associated with poorer response. Interpretation: Our data suggest that there is an association between the gut microbiota and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine may be important in mitigating anti-TNF-induced attenuation of the immune response. Funding: JLA is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-502), funded by Imperial College London and The Joyce and Norman Freed Charitable Trust. BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002). The Division of Digestive Diseases at Imperial College London receives financial and infrastructure support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. Metabolomics studies were performed at the MRC-NIHR National Phenome Centre at Imperial College London; this work was supported by the Medical Research Council (MRC), the National Institute of Health Research (NIHR) (grant number MC_PC_12025) and infrastructure support was provided by the NIHR Imperial Biomedical Research Centre (BRC). The NIHR Exeter Clinical Research Facility is a partnership between the University of Exeter Medical School College of Medicine and Health, and Royal Devon and Exeter NHS Foundation Trust. This project is supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care.

Introduction Acute severe ulcerative colitis (ASUC) traditionally requires inpatient hospital management for intravenous therapies and/or colectomy. Ambulatory ASUC care has not yet been evaluated in large cohorts.Aims We used data from PROTECT, a UK multicentre observational COVID-19 inflammatory bowel disease study, to report the extent, safety and effectiveness of ASUC ambulatory pathways.Methods Adults (≥18 years old) meeting Truelove and Witts criteria between 1 January 2019–1 June 2019 and 1 March 2020–30 June 2020 were recruited to PROTECT. We used demographic, disease phenotype, treatment outcomes and 3-month follow-up data. Primary outcome was rate of colectomy during the index ASUC episode. Secondary outcomes included corticosteroid response, time to and rate of rescue or primary induction therapy, response to rescue or primary induction therapy, time to colectomy, mortality, duration of inpatient treatment and hospital readmission and colectomy within 3 months of index flare. We compared outcomes in three cohorts: (1) patients treated entirely in inpatient setting; ambulatory patients subdivided into; (2) patients managed as ambulatory from diagnosis and (3) patients hospitalised and subsequently discharged to ambulatory care for continued intravenous steroids.Results 37% (22/60) participating hospitals used ambulatory pathways. Of 764 eligible patients, 695 (91%) patients received entirely inpatient care, 15 (2%) patients were managed as ambulatory from diagnosis and 54 (7%) patients were discharged to ambulatory pathways. Aside from younger age in patients treated as ambulatory from diagnosis, no significant differences in disease or patient phenotype were observed. The rate of colectomy (15.0% (104/695) vs 13.3% (2/15) vs 13.0% (7/54), respectively, p=0.96) and secondary outcomes were similar among all three cohorts. Stool culture and flexible sigmoidoscopy were less frequently performed in ambulatory cohorts. Forty per cent of patients treated as ambulatory from diagnosis required subsequent hospital admission.Conclusions In a post hoc analysis of one of the largest ASUC cohorts collected to date, we report an emerging UK ambulatory practice which challenges treatment paradigms. However, our analysis remains underpowered to detect key outcome measures and further studies exploring clinical and cost-effectiveness as well as patient and physician acceptability are needed.Trial registration number NCT04411784.

Background: In most areas of medical research, the label of ‘quality’ is associated with well-accepted standards. Whilst its interpretation in the field of medical education is contentious, there is agreement on the key elements required when reporting novel teaching strategies. We set out to assess if these features had been fulfilled by poster presentations at a major international medical education conference. Methods: Such posters were analysed in four key areas: reporting of theoretical underpinning, explanation of instructional design methods, descriptions of the resources needed for introduction, and the offering of materials to support dissemination. Results: Three hundred and twelve posters were reviewed with 170 suitable for analysis. Forty-one percent described their methods of instruction or innovation design. Thirty-three percent gave details of equipment, and 29% of studies described resources that may be required for delivering such an intervention. Further resources to support dissemination of their innovation were offered by 36%. Twenty-three percent described the theoretical underpinning or conceptual frameworks upon which their work was based. Conclusions: These findings suggest that posters presenting educational innovation are currently limited in what they offer to educators. Presenters should seek to enhance their reporting of these crucial aspects by employing existing published guidance, and organising committees may wish to consider explicitly requesting such information at the time of initial submission.