High But Inequitable COVID-19 Vaccine Uptake Among Patients with Inflammatory Bowel Disease.

Coronavirus disease 2019 (COVID-19) vaccines are recommended for all patients with inflammatory bowel disease (IBD).1 Patients with IBD historically have had low vaccine uptake relative to the general population.2 However, a recent survey suggested a rate higher than that of the general population with regard to COVID-19 vaccine intent among the IBD population. Their study was limited being that 96% of the patients surveyed identified as White, and 88% had attained a bachelor's degree or higher level of education.3 Therefore, these findings may not be representative of the IBD population as a whole. Previous studies have indeed identified disparities in influenza vaccine uptake within the IBD population.4,5.

Unraveling the contributions of hydrogen-bonding interactions to the activity of native and non-native ligands in the quorum-sensing receptor LasR.

Quorum sensing (QS) via the synthesis and detection of N-acyl L-homoserine lactone (AHL) signals regulates important pathogenic and mutualistic phenotypes in many bacteria. Over the past two decades, the development of non-native molecules that modulate this cell-cell signaling process has become an active area of research. The majority of these compounds were designed to block binding of the native AHL signal to its cognate LuxR-type receptor, and much effort has focused on LasR in the opportunistic pathogen Pseudomonas aeruginosa. Despite a small set of reported LasR structural data, it remains unclear which polar interactions are most important for either (i) activation of the LasR receptor by its native AHL signal, N-(3-oxo)-dodecanoyl L-homoserine lactone (OdDHL), or (ii) activation or inhibition of LasR by related AHL analogs. Herein, we report our investigations into the activity of OdDHL and five synthetic analogs in wild-type LasR and in nine LasR mutants with modifications to key polar residues in their ligand binding sites. Our results allowed us to rank, for the first time, the relative importance of each LasR:OdDHL hydrogen bond for LasR activation and provide strong evidence for the five synthetic ligands binding LasR in a very similar orientation as OdDHL. By delineating the specific molecular interactions that are important for LasR modulation by AHLs, these findings should aid in the design of new synthetic modulators of LasR (and homologous LuxR-type receptors) with improved potencies and selectivities.

A Practical Update on COVID-19 and Inflammatory Bowel Disease: COVID-19 Disease Risk and Vaccine Safety and Efficacy.

The COVID-19 pandemic introduced significant uncertainty regarding the care of patients with inflammatory bowel disease (IBD). Substantial research efforts have made progress in answering many of the questions that arose, but the constantly shifting paradigm of COVID-19-related research and recommendations has made it challenging for IBD clinicians to remain up-to-date. The goal of this article is to provide a concise and practical summary of the literature evaluating COVID-19 disease risk in addition to COVID-19 vaccine safety, immunogenicity, real-world effectiveness, and uptake among patients with IBD.

Higher and Sustained Cell-Mediated Immune Responses After 3 Doses of mRNA COVID-19 Vaccine in Patients With Inflammatory Bowel Disease on Anti-Tumor Necrosis Factor Therapy.

INTRODUCTION: Studies suggest that the generation of durable T-cell immunity following coronavirus disease 2019 (COVID-19) vaccination protects against severe disease. The aim of this study was to measure cell-mediated immune response (CMIR) 1-2 months and 6 months after a third dose of a COVID-19 mRNA vaccine. METHODS: This prospective study (HumoRal and CellULar initial and Sustained immunogenicity in patients with inflammatory bowel disease [IBD]) evaluated CMIR at 28-65 days (t 1 ) after dose 2, 28-65 days (t 2 ) (n = 183) and 6 months (±45 days) (t 3 ) (n = 167) after a third dose of an mRNA COVID-19 vaccine. A small cohort had blood sample available 28-65 days (t 4 ) (n = 55) after a fourth dose. Primary outcomes were CMIR at (t 2 ) and (t 3 ). Secondary outcomes included the effect of immunosuppressing IBD medications on CMIR and response at (t 4 ). RESULTS: All patients had measurable CMIR at all time points. CMIR increased at t 2 compared with that at t 1 (median 1,467 responding cells per million (interquartile range [IQR] 410-5,971) vs 313 (94-960) P < 0.001). There was no significant waning in t 2 vs t 3 or significant boosting at t 4 . Those on anti-tumor necrosis factor monotherapy had a higher CMIR compared with those not on this therapy at t 2 (4,132 [IQR 1,136-8,795] vs 869 [IQR 343-3,221] P < 0.001) and t 3 (2,843 [IQR 596-6,459] vs 654 [IQR 143-2,067] P < 0.001). In univariable analysis, anti-tumor necrosis factor monotherapy was associated with a higher CMIR at t 2 ( P < 0.001) and t 3 ( P < 0.001) and confirmed in a multivariable model ( P < 0.001). DISCUSSION: A third dose of a COVID-19 vaccine boosts CMIR, and the response is sustained in patients with IBD.

Uptake Rates of Three COVID-19 Vaccine Doses and Risk Factors for Incomplete Vaccination Among Patients With Inflammatory Bowel Disease Residing in Wisconsin: A Single-Center Cohort.

INTRODUCTION: Patients with inflammatory bowel disease on systemic corticosteroids may be at higher risk of adverse outcomes of COVID-19 infection, and vaccination is an essential preventive measure. Uptake of the original 2-dose COVID-19 messenger RNA (mRNA) primary vaccine series was previously high among patients with inflammatory bowel disease, while uptake of subsequent doses based on interval recommendations made by the Advisory Committee on Immunization Practice remains unknown. Herein, we evaluated uptake of 3 COVID-19 mRNA vaccine doses among patients with inflammatory bowel disease. METHODS: A total of 1012 patients were identified; 728 (71.9%) patients received 3 COVID-19 vaccine doses. Multivariable logistic regression revealed that younger age (odds ratio [OR] 1.02; 95% CI, 1.01 - 1.03; P = 0.001), rural status (OR 3.44; 95% CI, 2.17 - 5.56; P < 0.001), underrepresented minority status (OR 3.85; 95% CI, 1.89 - 7.69; P < 0.001), and absence of influenza vaccination (OR 8.17; 95% CI, 5.41 - 12.33; P < 0.001) were significantly associated with incomplete COVID-19 vaccination. RESULTS: Of 1362 patients, 83.3% completed a COVID-19 vaccination series. Younger patients had increased odds of not completing a COVID-19 vaccination series (mean [SD] 46.7 [14.7] vs 54.3 [15.8]; OR 1.03; 95% CI, 1.02-1.04; P < 0.001). Those who identified as non-White (1.88; 95% CI, 1.16-3.04; P = 0.010) or current smoker (1.85, 95% CI, 1.85-2.79; P = 0.004) had increased odds of not completing a COVID-19 vaccination series. Those who resided in rural ZIP codes (1.81; 95% CI, 1.35-2.43; P < 0.001), had not received a 2019-2020 influenza vaccine (5.13; 95% CI, 3.79-6.96; P < 0.001), or had lower comorbidity scores (2.95; 95% CI, 1.98-4.41; P < 0.001) had higher odds of not completing a COVID-19 vaccination series. CONCLUSIONS: Receipt of 3 COVID-19 mRNA vaccine doses is high overall among patients with inflammatory bowel disease. Younger age, underrepresented race/ethnicity, rural status, and lack of influenza vaccination are associated with incomplete COVID-19 vaccination.

Racial, Ethnic, and Geographic Disparities in Immunization Rates Among Patients With Inflammatory Bowel Disease.

Background and Aims: Racial and ethnic disparities exist in the treatment of IBD. These disparities exist in adult vaccine uptake among the general population and may extend to patients with IBD. The primary aim of this study was to determine whether racial, ethnic, or geographic disparities existed in influenza vaccine uptake among patients with IBD. Methods: We performed a multicenter, retrospective cohort study evaluating adult vaccine uptake among patients with IBD seen at two tertiary referral centers between September 2019 and February 2020. The primary outcome was to determine if racial/ethnic and geographic disparities existed in influenza vaccine uptake for the two prior seasons. Our secondary outcomes were to determine if disparities existed for pneumococcal, zoster, or hepatitis B vaccines. Results: Among the 2453 patients who met the inclusion criteria, most identified as non-Hispanic White (89.9%), were on immunosuppressive therapy (74.5%), and received the influenza vaccine in both seasons (56.0%). Older age (prevalence ratio (PR) 0.98; 95% confidence interval (95%CI) 0.98-0.99; P < .001) and non-Hispanic White patients (PR 0.76, 95%CI 0.59-0.98, P < 0.03) were significantly more likely to be immunized. Black patients (PR 1.37; 95%CI 1.18-1.59; P < .001) and those living in underserved geographic areas (PR 1.35; 95%CI 1.17-1.56; P < 0.001) were less likely to be immunized. Racial/ethnic and geographic disparities were identified for pneumococcal, zoster, and hepatitis B vaccine uptake. Conclusions: Racial and ethnic vaccination uptake disparities exist among patients with IBD; patients from medically underserved areas are also vulnerable to these disparities Studies identifying patient, provider, and system-level opportunities to address these disparities are needed.

Opportunistic use of dual-energy X-ray absorptiometry to evaluate lumbar scoliosis.

Low bone mineral density is associated with spinal deformity. Dual-energy X-ray absorptiometry (DXA), a modality that assesses bone density, portends a theoretical means to also assess spinal deformity. We found that DXA can reliably assess spine alignment. DXA may permit surveillance of spine alignment, i.e., scoliosis in the clinical setting. PURPOSE: Osteoporosis and scoliosis are interrelated disease processes. Dual-energy X-ray absorptiometry (DXA), used to assess bone density, can also be used to evaluate spinal deformity since it captures a posteroanterior (PA) image of the lumbar spine. We assessed the use of DXA to evaluate lumbar spine alignment. METHODS: A lumbar spine DXA phantom was used to assess the effects of axial and sagittal plane rotation on lumbar bone mineral content (BMC), density (BMD), and L1-L4 Cobb angle measurements. Using two subject cohorts, intra- and inter-observer reliability and validity of using DXA for L1-L4 Cobb angle measurements in the coronal and sagittal planes were assessed. RESULTS: Axial and sagittal plane rotation greater than 15° and 10°, respectively, significantly reduced measured BMD and BMC; there was minimal effect on Cobb angle measurement reliability. In human subjects, excellent intra- and inter-observer reliability was observed using lumbar PA DXA images for Cobb angle measurements. Agreement between Cobb angles derived from lumbar PA DXA images and AP lumbar radiographs ranged from good to excellent. The mean difference in Cobb angles between supine lumbar PA DXA images and upright AP lumbar radiographs was 2.8° in all subjects and 5.8° in those with scoliosis. CONCLUSIONS: Lumbar spine rotation does not significantly affect BMD and BMC within 15° and 10° of axial and sagittal plane rotation, respectively, and minimally affects Cobb angle measurement. Spine alignment in the coronal plane can be reliably assessed using lumbar PA DXA images.

Humoral Immunogenicity of 3 COVID-19 Messenger RNA Vaccine Doses in Patients With Inflammatory Bowel Disease.

Herein, we evaluated the humoral immunogenicity of a third coronavirus disease 2019 messenger RNA vaccine dose in patients with inflammatory bowel diseases. All patients displayed a humoral immune response, and median antibody concentrations were higher after the third dose than after completion of the 2-dose series.

Mutational analysis of the quorum-sensing receptor LasR reveals interactions that govern activation and inhibition by nonlactone ligands.

Gram-negative bacteria use N-acyl L-homoserine lactone (AHL) quorum-sensing (QS) signals to regulate the expression of myriad phenotypes. Non-native AHL analogs can strongly attenuate QS receptor activity and thereby QS signaling; however, we currently lack a molecular understanding of the mechanisms by which most of these compounds elicit their agonistic or antagonistic profiles. In this study, we investigated the origins of striking activity profile switches (i.e., receptor activator to inhibitor, and vice versa) observed upon alteration of the lactone head group in certain AHL analogs. Reporter gene assays of mutant versions of the Pseudomonas aeruginosa QS receptor LasR revealed that interactions between the ligands and Trp60, Tyr56, and Ser129 govern whether these ligands behave as LasR activators or inhibitors. Using this knowledge, we propose a model for the modulation of LasR by AHL analogs-encompassing a subtly different interaction with the binding pocket to a global change in LasR conformation.