Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases.

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.

Trends in inflammatory bowel disease infections and vaccinations in the past four decades: A high-level text mining analysis of PubMed publications.

AIM: We aimed at assessing the published literature on different prophylactic screening and vaccination options in inflammatory bowel disease (IBD) patients between 1980 and 2020. Special attention was attributed to latest data assessing covid-19 vaccinations. METHODS: We have queried PubMed for all available IBD-related entries published during 1980-2020. The following data were extracted for each entry: PubMed unique article ID (PMID), title, publishing journal, abstract text, keywords (if any), and authors' affiliations. Two gastrointestinal specialists decided by consensus on a list of terms to classify entries. The terms belonged to four treatment groups: opportunistic infections, prophylactic screening, prophylactic vaccinations/treatment, and routine vaccines. Annual trends of publications for the years 1980-2020 were plotted for different screening, vaccinations and infection types. Slopes of publication trends were calculated by fitting regression lines to the annual number of publications. RESULTS: Overall, 98,339 IBD entries were published between 1980 and 2020. Of those, 7773 entries belonged to the investigated groups. Entries concerning opportunistic infections showed the sharpest rise, with 19 entries and 1980 to 423 entries in 2020 (slope 11.3, p < .001). Entries concerning prophylactic screening rose from 10 entries in 1980 to 204 entries in 2020 (slope 5.4, p < .001). Both entries concerning prophylactic vaccinations/treatments and routine vaccines did not show a significant rise (slope 0.33 and slope 0.92, respectively). During the COVID 19 pandemic, a total of 44 publications were identified. Of them, 37 were relevant to vaccines and immune reaction. Nineteen publications (51%) were guidelines/recommendations, and 14 (38%) assessed immune reaction to vaccination, most of them (11, 61%) to mRNA vaccines. CONCLUSIONS: During the past two decades, along with a rapid increase in biologic therapy, publications regarding opportunistic infections and prophylactic screening increased in a steep slope compared to the two decades in the pre-biologic area. During the COVID-19 pandemic, most publications included vaccination recommendations and guidelines and only 38% included real-world data assessing reaction to vaccinations. More research is needed.

Innovation in Gastroenterology-Can We Do Better?

The health system can reap significant benefits by adopting and implementing innovative measures, as was recently demonstrated and emphasized during the COVID-19 pandemic. Herein, we present our bird's eye view of gastroenterology's innovative technologies via utilizing a text-mining technique. We analyzed five research fields that comply with innovation: artificial intelligence (AI), virtual reality (VR), telemedicine, the microbiome, and advanced endoscopy. According to gastroenterology literature, the two most innovative fields were the microbiome and advanced endoscopy. Though artificial intelligence (AI), virtual reality (VR), and telemedicine trailed behind, the number of AI publications in gastroenterology has shown an exponential trend in the last couple of years. While VR and telemedicine are neglected compared to other fields, their implementation could improve physician and patient training, patient access to care, cost reduction, and patient outcomes.

COVID-19 in Patients with Inflammatory Bowel Disease: The Israeli Experience.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet. OBJECTIVE: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies. METHODS: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes. RESULTS: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course (p = 0.001) and were less likely to be hospitalized (p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation. CONCLUSION: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome.

Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα.

BACKGROUND & AIM: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). METHODS: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally. RESULTS: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non-anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. CONCLUSIONS: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.