Abstract
Background and Aims
Evidence suggests patients with inflammatory bowel disease IBD receiving TNF antagonists have attenuated response to vaccination against COVID-19. We sought to determine ...the impact of IBD and of various medications for treatment of IBD on antibody responses to vaccination against COVID-19.
Methods
Patients with IBD n = 270 and healthy controls HC, n = 116 were recruited prospectively, and quantitative antibody responses were assessed following COVID-19 vaccination. The impact of IBD and of medications for treatment of IBD on vaccine response rates was investigated.
Results
Of HC, 100% seroconverted following complete vaccination with two vaccine doses; 2% of patients with IBD failed to seroconvert. Median anti-spike protein SP immunoglobulin IgG levels following complete vaccination in our IBD cohort was significantly lower than among HC 2613 AU/mL versus 6871 AU/mL, p ≤0.001. A diagnosis of IBD was independently associated with lower anti-SP IgG levels β coefficient -0.2, p = 0.001. Use of mRNA vaccines was independently associated with higher anti-SP IgG levels β coefficient 0.25, p ≤0.001. Patients with IBD receiving TNF inhibitors had significantly lower anti-SP IgG levels 2445 AU/mL than IBD patients not receiving TNF inhibitors 3868 AU/mL, p ≤0.001. Patients with IBD not receiving TNF inhibitors still showed attenuated responses compared with HC 3868 AU/mL versus 8747 AU/mL, p = 0.001.
Conclusions
Patients with IBD have attenuated serological responses to SARS-CoV-2 vaccination. Use of anti-TNF therapy negatively affects anti-SP IgG levels further. Patients who do not seroconvert following vaccination are a particularly vulnerable cohort. Impaired responses to vaccination in our study highlight the importance of booster vaccination programmes for patients with IBD.
Abstract
Background and Aims
Patients with inflammatory bowel disease IBD have an attenuated response to initial COVID-19 vaccination. We sought to characterize the impact of IBD and its treatment on ...responses after the third vaccine against SARS-CoV-2.
Methods
This was a prospective multicentre observational study of patients with IBD n = 202 and healthy controls HC, n = 92. Serological response to vaccination was assessed by quantification of anti-spike protein SP immunoglobulin IgG levels anti-SPIgG and in vitro neutralization of binding to angiotensin-converting enzyme 2 ACE2. Peripheral blood B-cell phenotype populations were assessed by flow cytometry. SARS-CoV-2 antigen-specific B-cell responses were assessed in ex vivo culture.
Results
Median anti-SP IgG post-third vaccination in our IBD cohort was significantly lower than HCs 7862 vs 19 622 AU/mL, p < 0.001 as was ACE2 binding inhibition p < 0.001. IBD patients previously infected with COVID-19 30% had similar quantitative antibody response as HCs previously infected with COVID-19 p = 0.12. Lowest anti-SP IgG titres and neutralization were seen in IBD patients on anti-tumour necrosis factor anti-TNF agents, without prior COVID-19 infection, but all IBD patients show an attenuated vaccine response compared to HCs. Patients with IBD have reduced memory B-cell populations and attenuated B-cell responses to SARS-CoV-2 antigens if not previously infected with COVID-19 p = 0.01. Higher anti-TNF drug levels and zinc levels <65 ng/ml were associated with significantly lower serological responses.
Conclusions
Patients with IBD have an attenuated response to three doses of SARS-CoV-2 vaccine. Physicians should consider patients with higher anti-TNF drug levels and/or zinc deficiency as potentially at higher risk of attenuated response to vaccination.
Helicobacter pylori (H. pylori) is the most common chronic bacterial infection. Treatment effectiveness remains a subject of debate considering bacterial antimicrobial resistance. Our aim was to ...analyze the diagnostic methods and eradication treatments for H. pylori infection in Serbia.
An observational multicenter prospective study was conducted in Serbia, as part of the European Registry on H. pylori Management (Hp-EuReg). Demographics, treatment indication, diagnostic methods, previous eradication attempts, and treatment were collected at AEG-REDCap e-CRF. Modified intention-to-treat (mITT) and per-protocol (PP) effectiveness analyses were performed. Safety, compliance, and bacterial antimicrobial resistance rates were reported. Data were quality checked.
Overall, 283 patients were included, with a mean age of 55 ± 15 years. Dyspepsia (n = 214, 77%) was the most frequent treatment indication, and histology (n = 144, 51%) was the most used diagnostic method. Overall eradication rate was 95% (PP) and 94% (mITT). Most prevalent first-line therapy was quadruple PPI + clarithromycin + amoxicillin + metronidazole, with a 96% effectiveness (p < 0.001). Second-line main treatment choice was triple amoxicillin + levofloxacin, with a 95% effectiveness (p < 0.05). Single-capsule Pylera® was the most prescribed third-line therapy, with 100% effectiveness (p < 0.05). Longer treatment duration was associated with a higher eradication rate in first-line therapy (p < 0.05). Clarithromycin and quinolone resistance rates in first-line were 24% and 8.3%, respectively. The overall adverse events' incidence rate was 13.4%, and therapy compliance was 97%.
Considering the high eradication rate, 14-day non-bismuth quadruple concomitant therapy is a reasonable first-line choice, while quinolone-based therapy and single-capsule Pylera® should be considered as rescue therapy options.
To determine the occurrence of intestinal and extraintestinal cancers in the 1993-2009 prospective European Collaborative Inflammatory Bowel Disease (EC-IBD) Study Group cohort.
A physician per ...patient form was completed for 681 inflammatory bowel disease patients (445UC/236CD) from 9 centers (7 countries) derived from the original EC-IBD cohort. For the 15-year follow up period, rates of detection of intestinal and extraintestinal cancers were computed.
Patient follow-up time was fifteen years. In total 62/681 patients (9.1%) 41 with ulcerative colitis/21 with Crohn's disease, 36 males/26 females were diagnosed with sixty-six cancers (four patients with double cancers). Colorectal cancer was diagnosed in 9/681 patients 1.3% (1 Crohn's disease and 8 ulcerative colitis). The remaining 53 cancers were extraintestinal. There was a higher prevalence of intestinal cancer in the Northern centers compared to Southern centers p=NS. Southern centers had more cases of extraintestinal cancer compared to Northern centers p=NS. The frequency of all observed types of cancers in Northern and in Southern centers did not differ compared to the expected one in the background population.
In the fifteen-year follow up of the EC-IBD Study Group cohort the prevalence of cancer was 9.1% with most patients having a single neoplasm and an extraintestinal neoplasm. In Northern centers there were more intestinal cancers while in Southern centers there were more extraintestinal cancers compared to Northern centers. In this IBD cohort the frequency of observed cancers was not different from that expected in the background population.
To determine the occurrence of intestinal and extraintestinal cancers in the 1993–2009 prospective European Collaborative Inflammatory Bowel Disease (EC-IBD) Study Group cohort.
A physician per ...patient form was completed for 681 inflammatory bowel disease patients (445UC/236CD) from 9 centers (7 countries) derived from the original EC-IBD cohort. For the 15-year follow up period, rates of detection of intestinal and extraintestinal cancers were computed.
Patient follow-up time was fifteen years. In total 62/681 patients (9.1%) 41 with ulcerative colitis/21 with Crohn's disease, 36 males/26 females were diagnosed with sixty-six cancers (four patients with double cancers). Colorectal cancer was diagnosed in 9/681 patients 1.3% (1 Crohn's disease and 8 ulcerative colitis). The remaining 53 cancers were extraintestinal. There was a higher prevalence of intestinal cancer in the Northern centers compared to Southern centers p=NS. Southern centers had more cases of extraintestinal cancer compared to Northern centers p=NS. The frequency of all observed types of cancers in Northern and in Southern centers did not differ compared to the expected one in the background population.
In the fifteen-year follow up of the EC-IBD Study Group cohort the prevalence of cancer was 9.1% with most patients having a single neoplasm and an extraintestinal neoplasm. In Northern centers there were more intestinal cancers while in Southern centers there were more extraintestinal cancers compared to Northern centers. In this IBD cohort the frequency of observed cancers was not different from that expected in the background population.
Continuous evaluation of the actual clinical practice of diagnosis and treatment of Helicobacter pylori is crucial in order to provide the best standard of care and to compare health outcomes with ...expert recommendations.
Aim:to evaluate the effectiveness of the standard triple therapy (amoxicillin, clarithromycin, a proton pump inhibitor) and the standard triple therapy plus bismuth tripotassium dicitrate.
Materials and methods.Observational, prospective, multicenter study, carried out in one single Russian centre A.S. Loginov Moscow Clinical Scientific Center as part of the Hp-EuReg. Patients were included from 2013 to November 2019 by Russian gastroenterologists.
Results.A total of 647 patients were collected and 330 were administered either standard triple therapy ((amoxicillin, clarithromycin, a proton pump inhibitor) or standard triple therapy plus bismuth tripotassium dicitrate. Invasive methods is dominates in the initial diagnosis of H. pylori: the frequency of use of the quick urease test decreased from 50% in 2013 to 31% in 2019. Serology was used in 27.9%. There has been an increase in the use of the13C-urea breath test from 13% in 2013 to 31% in 2019. The histological method (7.5%) and the stool antigen test (3.2%) were used less frequently. For eradication control non-invasive methods are mostly used:13C-UDT (82.7%) and the stool antigen test (14.4%). The effectiveness of standard triple therapy (mITT) was 68% with a 7-day course, 79% with a 10-day course, and 70% with a 14-day course. Combination of bismuth and standard triple therapy eradicates H. pylori (mITT) in 63%, 75% and 89%, respectively.
Conclusion.An improvement in the clinical practice of managing patients with H. pylori infections has been noted. The standard triple therapy in combination with bismuth tripotassium dicitrate, prescribed for 14 days, is more effective.
1 Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College, University of Dublin, Dublin 2, Ireland 2 Centre for DNA Fingerprinting and Diagnostics (CDFD), Nacharam, ...Hyderabad, 50 00076 India 3 Owaisi Hospital and Research Centre, Deccan College of Medical Sciences, Kanchanbagh, Santoshnagar, Hyderabad, India 4 Department of Gastroenterology, The Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland
Correspondence Cyril J. Smyth csmyth{at}tcd.ie
Received August 20, 2003
Accepted February 12, 2004
Sequence variations located at the signal sequence and mid-region within the vacA gene, the 3'-end of the cagA gene, the indel motifs at the 3'-end of the cag pathogenicity island and the regions upstream of the vacA and ribA genes were determined by PCR in 19 paired antral or antrum and corpus Helicobacter pylori isolates obtained at the same endoscopic session, and three antral pairs taken sequentially. Random amplification of polymorphic DNA (RAPD)-PCR and fluorescent amplified fragment length polymorphism (FAFLP)-PCR fingerprinting were applied to these paired clinical isolates. The FAFLP-PCR profiles generated were phylogenetically analysed. For the 22 paired isolates there were no differences within pairs at five of the genetic loci studied. However, six pairs of isolates (27 %), of which four were antrum and corpus pairs, showed differences in the numbers of repeats located at the 3'-end of the cagA gene. RAPD-PCR fingerprinting showed that 16 (73 %) pairs, nine of which were antrum and corpus pairs, possessed identical profiles, while six (27 %) displayed distinctly different profiles, indicating mixed infections. Three of the six pairs showing differences at the 3'-end of the cagA gene yielded identical RAPD-PCR fingerprints. FAFLP-PCR fingerprinting and phylogenetic analysis revealed that all 16 pairs that displayed identical RAPD-PCR profiles had highly similar, but not identical, fingerprints, demonstrating that these pairs were ancestrally related but had undergone minor genomic alterations. Two antrum and corpus pairs of isolates, within the latter group, were isolates obtained from two siblings from the same family. This analysis demonstrated that each sibling was colonized by ancestrally related strains that exhibited differences in vacA genotype characteristics.
Present Address: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599-7264, USA.
Abbreviation: FAFLP, fluorescent amplified fragment length polymorphism.
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