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Background Patients with celiac disease (CeD) reported increased COVID-19 vaccine hesitancy due to a fear of adverse events (AEs). However, the risk of AEs post-COVID-19 vaccination in patients with CeD is unknown. Purpose To assess whether the rate of common side effects (SEs) and AEs due to COVID vaccines are higher in patients with CeD compared to a non-CeD population. Method We conducted a collaborative international cross-sectional study in 16 countries between April 2022 and July 2022. An online survey was distributed to patients with CeD through patients' local societies, and to non-CeD from the general population in each country through social media posts, word-of-mouth, and through academic institutions. We collected data on participant demographics, medical conditions, CeD diagnosis, GFD adherence, history of COVID-19 vaccinations (type and doses) and self-reported SEs and AEs post-COVID-19 vaccine. SEs included pain/swelling at the site, fatigue, fever, chills, nausea and/or headaches. AEs included thrombosis, myocarditis, anaphylactic reaction, and hospitalization related to the vaccine. Logistic regression models were used to assess predictors such as CeD diagnosis, age, gender, vaccine type and comorbidities on the likelihood of reporting SEs and AEs post-vaccine. Result(s) : A total of 17,795 participants completed the survey, 13,638 with CeD (median age of 45[27]) and 4,157 non-CeD controls (median age of 43[20]). There were no significant differences in sex between CeD and controls. Overall, CeD patients had similar odds of SEs compared with non-CeD individuals (aOR=1.02;95% CI=0.92-1.14). SEs were slightly increased only in the second dose of the vaccine in the CeD population compared to non-CeD individuals (aOR= 1.35;95% CI=1.19-1.53). The most common reported SEs in CeD and controls were pain/swelling at the injection site (29% vs 23 %, p< 0.0001) and fatigue (29% vs 24%, p<0.0001). The odds of SEs were higher with Moderna Spikevax, AstraZeneca/Oxford and Johnson and Johnson vaccines than after the Pfizer vaccine (p< 0.0001). The overall rate of AEs post-vaccine was similar between patients with CeD and non-CeD individuals (aOR= 1.29;95% CI= 0.89-1.87). Overall, female gender, older age, GFD adherence, respiratory conditions, obesity and receiving immunosuppressive medications increased the odds of SEs, while only age and a history of allergies increased the odds of AEs. Conclusion(s) In this large international study, patients with CeD reported similar rates of SEs and AEs post-COVID vaccine compared to non-CeD individuals. This information is highly relevant as it addresses the main concern leading to COVID-19 vaccine hesitancy in CeD patients. Disclosure of Interest None Declared
ABSTRACT
Introduction: Increased inflammatory cytokines has been observed in COVID-19 patients and there is evidence showing an alteration in gut-microbiota composition. SARS-CoV-2 can cause gastrointestinal symptoms, such as diarrhea. Evidence of an altered gut-microbiota composition and cytokines levels in COVID-19 diarrhea patients is lacking. Objectives: To compare serum cytokine levels and gut microbiota between COVID-19 diarrhea (D-COVID- 19) and non-diarrhea (NonD-COVID-19) patients and non- COVID-19 controls (HC). Material and methods: We included 143 hospitalized COVID-19 patients (positive quantitative reverse transcription PCR) in a single University Hospital, and 53 ambulatory HC (negative rapid serological test) were included. Blood and stool samples were collected at hospital admission in COVID-19 patients and at the time of HC recruitment. 27- pro and anti-inflammatory cytokines (Bio-Plex Pro™, Bio- Rad) were measured. Gut microbiota composition and diversity profiles were characterized by sequencing the 16S rRNA gene V3-V4 region amplified using DNA extracted from stool samples. Bioinformatics analysis was performed with QIIME2 software. First, we compare cytokine levels between COVID- 19 and HC and then COVID-19 with and without diarrhea. All comparisons were adjusted for age, sex, and BMI with linear regression. Results: The mean age in COVID-19 patients was 54 +/- 15 years (F=50%) and 52 +/- 8 (F=62%) for HC. Diarrhea was present in 19 (13.29%) of COVID-19 patients. COVID-19 patients had significative higher levels of: IL- 1ra, IL-2, IL-6, IL-7, IL-8, IL-13, IP-10 and PDGF-bb. Significant lower values of: IL-9, FGF -basic, MIP-1β, TNF-α were observed in D-COVID-19 compared to NonD-COVID-19. COVID-19 patients had a significant reduction of bacterial species (p=0.0001), and diversity and complexity of the bacterial community (Shannon's index) (p=0.0001) compared to the HC. There was no difference between D-COVID-19 and NonD-COVID-19. There were also changes in the composition of the microbiota associated with COVID-19. At the phylum level, COVID-19 patients showed a significant decrease in Actinobacteria and Firmicutes, and an increase in Bacteroidetes. At species level, an increase of 4 species of the genus Bacteroides was observed in COVID-19 patients. 31 very diverse bacterial species were found, all decreased in D-COVID-19. Conclusions: An alteration in serum cytokine levels was observed between COVID-19 and HC. D-COVID-19 had a decrease in some proinflammatory cytokines. A significant decrease in richness and species diversity of gutmicrobiota was observed in COVID-19 patients compared to HC, but no significant differences were observed between D-COVID-19 and NonD-COVID-19. However, in D-COVID- 19, a decrease in some bacterial species was observed.(Table Presented)(Figure Presented)
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INTRODUCTION: Irritable bowel syndrome (IBS) is a functional disorder with high prevalenceimpacting on patient’s quality of life. IBS is considered a multifactorial entity, in whichsocioemotional factors and social stress might play a central role in the generation andworsening of symptoms. The mandatory lockdown in response to SARS CoV-2 pandemic,represents a unique scenario of reduced social interaction and complexity, potentially impactingthe IBS-patients’ symptoms evolution. OBJECTIVE: To evaluate the impact of the mandatorylockdown due to the SARS CoV-2 pandemic on the brain-gut axis symptomatology inIBS patients. MATERIAL AND METHODS: All IBS-diarrhea and mixed bowel habits patternsubtype patients, from an existing Rome IV-defined cohort database, were invited to participate(n = 129, mean age 54 [+/-16], 78% female). Patients were assessed via an onlinesurvey or phone interview. The survey included Irritable Bowel Syndrome Severity Scale(IBS-SS), Likert scale, as well as measures of Bristol scale, anxiety and depression andsomatization. Further, patients were asked about comorbidities (pyrosis and/or regurgitation,dyspepsia, chronic fatigue, fibromyalgia, non-migraine headache, weight and eating habits).Most of this data was compared with pre-pandemic existing data. RESULTS: During lockdown,there was a significant decrease in severe IBS patients’ proportion (50.39 % vs 30%, p=0.000) compared to the pre pandemic state. Before pandemic, this cohort of patientshad a mean IBS-SS of 278.54 (+/- 88.64) compared to 212.36 (+/-117.50) during lockdown(difference -65.9 [95% CI: -89.4 to – 42.4];p = 0.000). Likewise, there was a decrease ofone average point on the Likert Scale on global IBS symptoms, pain, and distension, as wellas an improvement in stool consistency (2-point average decrease on Bristol Scale). Similarly,anxiety and somatization scores were improved and there was a significant decrease infibromyalgia and chronic fatigue symptoms during lockdown (in comparison with prepandemictimes). Conversely, headache and pyrosis and/or regurgitation symptoms increasedsignificantly. These effects remained when adjusted for confounders (age, sex, anxiety, anddepression), evidencing that the mandatory lockdown represented an independent protectivefactor for severe IBS-symptoms (OR 0.39, 95% CI 0.18-0.87;p=0.02). CONCLUSION: Incomparison with a pre-pandemic period, there was a significant improvement in IBS-severitysymptoms, anxiety and somatization during the SARS CoV-2 pandemic and mandatorylockdown. Lesser exposure to external stress burden during lockdown could have beeninvolved in a better control of affecting gut-brain axis factors.(Table Presented)(Image Presented)
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INTRODUCTION: There is evidence that the gut microbiota and its relationship with the immune system could be involved in the pathogenesis of COVID-19. SARS-CoV-2 can cause gastrointestinal symptoms during the early phases of the disease. Intestinal dysfunction induces changes in intestinal microbes, and an increase in inflammatory cytokines. Therefore, microbiota modulation could play a role in COVID-19 treatment. Tannins have been shown to work as prebiotics on the gastrointestinal microbiota. In particular, quebracho and chestnut tannins have shown to regulate the immune response and decrease in vitro-cytokines production, through microbiota fermentation-secondary metabolites, such as quercetin and SCFAs. OBJECTIVE: To evaluate the efficacy and the effect on cytokine levels of a tannin specific natural extract in COVID-19 patients. MATERIAL AND METHODS: This prospective, doubleblind, and randomized study was approved by the Hospital de Clínicas, José de San Martín (Buenos Aires, Argentina). Blood and stool samples were collected at baseline (Day 0) and after treatment (Day 14) during July-October 2020, with final follow-up in November 2020. We randomly assigned 124 RT-PCR confirmed COVID-19 cases (>18 years) to receive oral dry extracts of quebracho and chestnut tannins (240 mg) and B12 vitamin (0.72 μg) or placebo, twice daily for 14 days as adjunct treatment to their standard of care management. 27-pro and anti-inflammatory cytokines were measured on day 0 and 14 (Bio-Plex Pro™, Bio-Rad). Final enrollment of 140 patients with matched fecal microbiome characterization (16S, WGS and metabolites) is expected. RESULTS. Of 124 patients who were randomized (mean age 55+/-15, 63 [50.81%] male), 121 (97.58%) completed the trial. No adverse events were observed in the tannin group. Patients presenting with diarrhea (13%) had a trend to have elevated blood MIP-1α levels, which were significantly reduced by tannin treatment (Table 1). At baseline, higher levels of MIP-1α were also associated with diagnosis of pneumonia (Fig. 1), which was maintained after adjusting for confounders (age, sex, diabetes;p=0.04). Moreover, at baseline there was a positive correlation between MIP-1 α and IL-1ra, IL-2, MIP-1b and TNF-α, with all of these cytokines decreasing mostly with tannin treatment. CONCLUSION: To our knowledge, this clinical trial represents the first study to target the gut microbiome in hospitalized COVID-19 patients. Oral tannins as adjunct treatment with standard-of-care management of these patients significantly reduced proinflammatory cytokine levels that are generally associated with poor predictive outcomes, i.e. pneumonia and diarrhea. Further, our prospective studies will determine which microbiome-mediated mechanisms may attenuate the cytokine storm that is evident in COVID-19 disease pathogenesis. (Table presented) (Figure presented)