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1.
Journal of Hepatology ; 77:S14, 2022.
Article in English | EMBASE | ID: covidwho-1967492

ABSTRACT

Background and aims: Approval of a drug therapy for NASH requires a very good safety/tolerability profile and acceptable therapeutic index. MAESTRO-NAFLD-1 (NCT04197479) is a randomized doubleblind (DB) Phase 3 clinical trial of placebo (PBO) versus resmetirom (RES), a once-a-day oral selective thyroid hormone receptor β agonist, in >1100 patients with NAFLD with safety as the primary end point. Method: Enrollment was Dec 2019 to Oct 2020 at 79 US sites. Requirements included 3 metabolic risk factors, fibroscan (FS) ≥5.5 kPa/CAP≥280 dBm, MRI-PDFF≥8%. Randomization was 1:1:1:1 to 3 DB arms, PBO, 80 or 100 mg RES (n = 972) or an 100 mg open label (OL) arm (n = 171). The primary objective was to evaluate the safety and tolerability of 80 or 100 mg RES versus PBO measured by the incidence of adverse events (AEs). Results: At baseline the DB safety population (n = 969) was age 55.9 (11.8);female, 54.4%, white 88.6%;hispanic 34.7%;BMI 35.3 (6.0) type 2 diabetes 49%, hypertension 76.1%, dyslipidemia 87.9%;FS 7.4 (4.7) kPa. Discontinuations (22.5%) did not differ by treatment, most patient decision (pandemic related). DB compliancewas impacted by COVID drug kit delays. AE withdrawals were 80 mg, 2.4%;100 mg, 2.8%;PBO, 1.3%. The primary objective was met. TEAEs were 80 mg, 88.4%;100 mg, 86.1%;PBO, 81.8%. TEAEs ≥grade 3 severity were 80 mg, 7.6%;100 mg, 9.0%;PBO, 9.1%. AEs in excess of PBOwere grade 1–2 AEs of diarrhea (80 mg, 23.5%;100 mg, 31.2%;PBO, 13.8%) and nausea (80 mg, 11.9%;100 mg, 18.2%;PBO, 7.9%), in the first few weeks. ALT increases ≥3XULN were 80 mg, 0.61%;100 mg, 0.31%;PBO,1.6%. Therewere no changes in bodyweight or HR. BP decreased by 2–3 mmHg in the RES arms. Key 2o end points were met (Table). Comparative mean reduction in FS VCTE was not significant;a responder analysis of FS and MRE showed significant reductions with RES treatment. Conclusion: RES achieved the primary safety end point in this 52- week Phase 3 NAFLD clinical trial that identified patients by metabolic risk and non-invasive imaging. Key 2o end points were met including LDL-C, ApoB, triglycerides, MRI-PDFF, FS (CAP).(Table Presented) 1MRE combined RES groups.

2.
Gastroenterology ; 162(7):S-1101-S-1102, 2022.
Article in English | EMBASE | ID: covidwho-1967409

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)

3.
Gastroenterology ; 162(7):S-1033, 2022.
Article in English | EMBASE | ID: covidwho-1967401

ABSTRACT

Introduction: COVID-19 has had a major impact on public health during the last two years. Classic symptoms like fever, cough, and loss of smell and taste are well known. Gastrointestinal symptoms, however, are often not questioned and therefore potentially underestimated. Aim: The aim of this study was to evaluate the prevalence of gastrointestinal symptoms during COVID-19 infection. Methods: A digital questionnaire was used to evaluate symptoms in patients suffering from COVID-19 infection. It was distributed via a patient centered informative website, COVID testing facilities, and the University of Antwerp. The questionnaire contained questions evaluating characteristics of the infection, treatment, general symptoms, and gastrointestinal symptoms. Results: 489 questionnaires were completed, and 430 participants had a confirmed COVID-19 infection. Only data of confirmed cases was used in further analyses. Most patients (76.5%) were diagnosed with PCR testing (63% nasopharyngeal swab, 12.9% saliva, 0.6% combination of both), 7.2% were diagnosed based on serology in blood, 3.1% anamnestic by their treating physician, and 1.2% with other methods like imaging. Of our population, only 6.1% was hospitalized and 12.5% received antibiotics. Two patients (0.5%) were completely asymptomatic. The most prevalent general symptoms were fatigue (76.5%), headache (62.1%), loss of smell (60.0%), muscle aches (59.5%), loss of taste (56.7%), fever (55.6%), and cough (53.0%). All other symptoms like sore throat, rhinorrhea, chest pain, and dyspnea occurred in less than half of our population. A large number (82.1%) of patients had at least one gastrointestinal symptom. The most prevalent symptoms were diarrhea and anorexia (both 52.1%) followed by abdominal pain (50.5%), nausea (40.7%), and vomiting (14.4%). Conclusion: Individual gastrointestinal symptoms were less prevalent than most general symptoms. However, most patients in our study did have at least one gastrointestinal symptom. This demonstrates the importance of inquiring about gastrointestinal symptoms when seeing COVID-19 patients. A potential bias in our study is the possibility that patients suffering from gastrointestinal complaints were more inclined to participate in this study thereby increasing the prevalence of reported symptoms.

4.
Gastroenterology ; 162(7):S-1006-S-1007, 2022.
Article in English | EMBASE | ID: covidwho-1967394

ABSTRACT

Introduction Since inflammatory bowel disease (IBD) patients were excluded from vaccine authorization studies, limited knowledge exists regarding perceptions for and unfavorable effects of COVID-19 vaccination in this group. The aim of this study was to investigate the real world use and adverse events (AE) of vaccines against COVID-19 in IBD patients. Aims and Methods Fully vaccinated IBD patients followed in Greek centers were invited to participate in an anonymous online self reporting survey that included information regarding their demographics, clinical characteristics, treatment, vaccination perceptions and potential AE. Patients were vaccinated with either messenger-RNA or viral vector vaccines that are currently EMA approved. AE were stated as any kind of new symptom or sign onset, including localized (at the injection site) or systematic ones (fatigue, headache, allergic reactions, fever, lymphadenopathy, myalgias/arthralgias and gastrointestinal disorders). Results A total of 1007 IBD patients [male 50.5%, median age (IQR) 44 (35-55) years, Crohn's disease 64.3%, history of COVID-19 infection 2.6%] who completed the survey after they have fulfilled their vaccination program were included. Detailed demographics and clinical characteristics of the study population are presented in Table 1. More than half of the patients (51%) stated that they show confidence in vaccination whereas the rest although hesitant admitted the protection it offers. The median (IQR) time between 2nd vaccine dose and questionnaire completion was 15 (5-43) days. There were no serious AE leading to emergency room visit or hospitalization. Total AE were reported by 81% after dose 1 (D1) and 76% after dose 2 (D2), reduced to 44% and 51% when excluding isolated injection site reactions respectively. Systemic AEs were more common after D2 (P<0.0001). Very few patients reported new onset abdominal symptoms [abdominal pain 4% (D1), 6% (D2) and diarrhea 5% (D1), 7% (D2)]. In the multiple regression analysis AE occurrence was positively associated with young age, female gender and blood type AB rhesus positiveafter both doses, whereas inactive disease was negatively associated with AE only in D1 (p= 0.044) No association with the use of medications including advanced therapy was found (p>0.05), except from corticosteroids after D2 (p=0.003) but it was a small (32/1007 patients) heterogenous (monotherapy, double or triple immunosupression) sample to draw conclusions (Table 2). Conclusions The presence of SARs-CoV-2 vaccination AE in Greek patients with IBD is similar to the reported in other populations. Young age and female gender but not IBD related medications are associated with the development of AEs after both doses. (Table Presented) (Table Presented)

5.
Gastroenterology ; 162(7):S-845, 2022.
Article in English | EMBASE | ID: covidwho-1967374

ABSTRACT

INTRODUCTION: According to ROMA IV (R-IV), in schoolchildren and adolescents in Colombia and Ecuador, the prevalence to present some functional gastrointestinal disorder (FGID) is 21.2%-22.3% being the main FGID the functional constipation (FC). There’s no data about infants and toddlers in latinoamerican countries (Latam). OBJECTIVE: To describe the prevalence of FGIDs in children in 3 Latam countries according to R-IV. METHODS: 11493 children in Colombia, Ecuador and Panama were included: 1382 infants aged 0-12 months (Group A, 7.3+/-3.7 months), 2631 toddlers aged 1-4 years (Group B, 2.5+/-0.9 years old), 2791 schoolchildren aged 8-12 years (Group C, 10.6+/-1.2 years) and 4689 adolescents aged 13-18 years (Group D, 14.8+/-1.4 years). FGIDs were identified through the Questionnaire of Pediatric Gastrointestinal Symptoms Rome IV (QPGS-IV). RESULTS: The prevalence to present some FGID was 15.8% in infants;23.3% in toddlers;21.1% in schoolchildren and 22.1% in adolescents;being the most frequent FGDI in the Group A, colic (7.6%), regurgitation (6.4%) and FC (4.7%);in the Group B, FC (17.6%), cyclic vomiting syndrome (5.4%) and functional diarrhea (0.3%);in the Group C, FC (12.5%), functional dyspepsia (2.8%) and irritable bowel syndrome (1.8%), and the Group D, FC (11.1%), functional dyspepsia (3.9%) and functional abdominal pain (1.9%). There were more FGDIs in infants with caesarean section (OR=1.7 95%CI=1.22-2.41 p=0.0010), toddlers with previous diarrhea (OR=1.7 95% CI=1.39-2.23 p=0.0000), in schoolchildren with previous dengue infection (OR=2.0 95%CI=1.24-3.25 p=0.0019) and adolescents in covid-19 confinement (OR=1.4 95%CI =1.13-1.78 p=0.0013). CONCLUSIONS: The prevalence for FGIDs was lower in infants whose main FGDI was colic;the FC was one of the main FGIDs in all the age groups, being associated in children younger than 4 years old to caesarean section and history of diarrhea and children between 8-18 years old to history of dengue and confinement.

6.
Gastroenterology ; 162(7):S-592-S-593, 2022.
Article in English | EMBASE | ID: covidwho-1967334

ABSTRACT

Background: Inflammatory bowel disease (IBD) and IBD-related biologic therapies are not associated with worse outcomes of Coronavirus Disease 2019 (COVID-19), however, data are lacking regarding the long-term impact of COVID-19 and its inflammatory sequelae on the disease course of IBD. We aimed to investigate the long-term outcomes of patients with IBD and COVID-19. Methods: We performed a multicenter matched case-control study of patients with IBD [Crohn's disease (CD), ulcerative colitis (UC)] and COVID-19 between February 2020 and December 2020 at 5 large health systems. Cases were defined by the presence of COVID-19-related symptoms and confirmatory SARS-CoV-2 PCR or IgG testing. Non-COVID controls were defined as absence of symptoms and both a negative PCR and IgG during the study entry period. Cases were matched 1:1 to controls based on age, sex and IBD type. The primary composite outcome was IBD-related hospitalization or surgery, and outcomes were sub-stratified by COVID-19 severity. Results: We identified 251 cases with IBD [UC (n=111, 44%), CD (n=139, 55%)] and confirmed COVID-19, matched with 251 non-COVID-19 IBD controls, with a median follow-up of 394 days. COVID-19 patients had higher rates of prior IBD-related hospitalizations (36% vs. 27%;P=0.03), corticosteroid use (75% vs. 65%;P=0.06), and biologic exposure (73% vs. 64%;P=0.04) than controls. There were no differences in UC extent or CD phenotype between groups. In COVID-19 positive patients, the most common symptoms were fever (61%), cough (48%), fatigue (30%) and diarrhea (28%). Severe COVID-19 (defined as hospitalization, ICU requirement or mechanical ventilation) occurred in 16% (n=39) of cases. The primary composite outcome of IBD-related hospitalization or surgery occurred in 12% (n=38) of cases vs. 15% (n=29) of controls (P=0.24;Table 1). When further stratified by COVID-19 severity, the incidence of the primary composite outcome was highest in patients with severe COVID-19, followed by controls and non-severe COVID-19 (Figure 1). Under multivariate Cox regression, severe COVID-19 remained a predictor of worse IBD outcomes (aHR 2.09, 95% CI 0.91-4.86) whereas non-severe COVID-19 was associated with decreased risk (aHR 0.52, 95% CI 0.28- 0.99). Prior IBD-related hospitalization or surgery (aHR 3.10, 95% CI 1.70-6.57) and current steroid use (aHR 2.17, 95% CI 0.95-4.94) were also predictive of worse IBD outcomes. Conclusion: In this matched case-control study, a history of any COVID-19 infection did not appear to exacerbate the course of IBD, however, severe COVID-19 was associated with worse IBD outcomes. These data suggest that the inflammatory sequelae of COVID-19 may adversely impact the subsequent disease course of IBD. Further studies are required to confirm these associations, which underscore the importance of COVID-19 mitigation measures.(Table Presented) (Figure Presented)

7.
Gastroenterology ; 162(7):S-488, 2022.
Article in English | EMBASE | ID: covidwho-1967321

ABSTRACT

Introduction: COVID-19 pandemic reportedly caused a significant increase in the utilization of all healthcare sectors. The surge of cases was attributed to the new variants of the virus causing more burden on the system. One of the helpful tools to increase awareness and reduce the chance of transmission is the early recognition of COVID-19 infection symptoms. Educating the public about these symptoms may help patients to seek medical attention early, and be cautious about exposing others to the virus. A significant percentage of infected patients visited our center due to COVID-19 presented with gastrointestinal symptoms. We are reporting our experience related to these issues. Methods: Data was cross-sectional and collected from 2334 charts for patientspresented to the center during the period between 7/26/2021 - 8/11/2021. We collected patients' demographics, vaccine status, reasons for the visit and all presenting symptoms. Abbott Rapid PCR test was used to confirm the infection. We also collected data regarding the visits to the center during the same period in 2017, 2018, 2019, and 2020 for comparison. Results: There has been a significant increase in healthcare utilization due to COVID-19 over previous years during the same periods. In 2017, 2018, and 2019 the average number of visits were 464, while in 2020 the total number was 1387 visits, of which 998 were COVID-19 related visits. In 2021, total visits were 2334 of which 1785 wereCOVID-19 related. These values indicate a 3- and 5-folds' increase in the number of visits respectively, with about 75% of the visits during the last two years being COVID-19 related. 265 Out of the 567 COVID-19 positive patients reported at least one GI symptom, 47 % overall (50% females and 43% males), the loss of taste was 26% (28% females and 25% males), nausea was 22% (23% females, 20% males), diarrhea was 20% (19% females and 20% males), and vomiting was 8% (7% females and 8% males). There were significant differences in symptoms rate between vaccinated and unvaccinated individuals (unvaccinated 48.9%, vaccinated 38.3%). Conclusion: The study demonstrates a significant burden of the current COVID-19 surge on the healthcare system in comparison to previous years. 14% of the COVID-19positive patients were asymptomatic, being tested due to exposure. Most of the patients were symptomatic, 47% of COVID-19 positive patients presented with at least one GI symptom. Symptoms are more prevalent among unvaccinated

8.
Gastroenterology ; 162(7):S-487, 2022.
Article in English | EMBASE | ID: covidwho-1967319

ABSTRACT

Background and Aims: Cancers are known to worsen the clinical course of SARS-CoV-2 infection. We aimed to assess health outcome effectors in Coronavirus 19 (COVID-19) cancer patients from different centers in the US. Methods: We retrospectively evaluated medical records of 364 COVID-19 cancer patients from 3 centers in the US (New York, Michigan, and DC) admitted to the hospital between Dec. 2019 to Oct. 2021. Outcomes, symptoms, labs, and comorbidities of cancer patients with COVID 19 (Cases), were analyzed and compared with non-cancer COVID-19 patients (Controls). Results: Among 1934 hospitalized COVID-19 patients, 18.7% (n=364) have an active or previous history of cancer. Cancer patients were older when compared with non-cancer controls (69.7 vs 61.3 years). Among these 364 cancer patients, 222 were African Americans (61.7%) and 121 were Caucasians (33.2%). Cancer patients had an increased length of hospitalization compared to controls (8.24 vs. 6.7 days). The most common types of cancer in cases are prostate cancer (41.5%) and hematological malignancies (10.1%) among males, and breast cancer (41.5%), and head and neck cancers (11.4%) in females. In both genders, lung cancer is associated with high mortality. Patients with a previous history of cancer were more prone to death (p=0.04) than active cancer patients. Cough (23.1%) and fever (19.5%) are the most common symptoms among the cases. In univariate and multivariate analyses, predictors of death among cancer patients were male sex, older age, African American ethnicity/race, asthma, presence or absence of fever, elevated troponin, mechanical ventilation, and previous history of cancer. There is no significant difference in mortality in cancer patients when compared to controls. Abdominal pain (2.2%), diarrhea (3.8%), and vomiting (2%) occurred both in cases and controls but did not associate with death. Albumin is also significantly associated with mortality in cases (p=0.042). AST (54.6%), ALT (12.5%), and Bilirubin (16%) were elevated in the majority of cases. Both AST and ALT alterations have an effect on mortality. Univariate analysis shows that AST is strongly and significantly associated with mortality in cases (p=0.001) but not in controls. ALT is also associated with mortality in cases at the 10% level (p=0.057). Diarrhea is strongly associated with mortality in control (p <0.001) but not in cases. Conclusion: In this retrospective cohort study, we found male sex, and African American race is associated with high mortality. Elevated troponin levels and LFT’s during the hospital stay were significantly associated with poor outcomes. Patients with a previous history of cancer were more prone to death when compared to active cancer COVID-19 patients. Early recognition of cancer COVID-19 patients can help determine appropriate treatment and management plans for better prognosis and outcome.

9.
Gastroenterology ; 162(7):S-365, 2022.
Article in English | EMBASE | ID: covidwho-1967300

ABSTRACT

Introduction: Gastrointestinal symptomatology in SARS-CoV-2 infection is a common clinical presentation, reported in up to 61% in those affected, being the presence of acute diarrhea one of the most common symptoms, reported in up to 33.7%. There are multiple theories about physiopathological mechanisms of diarrhea associated with SARS-CoV2 infection, but there is not enough evidence to attribute this symptom only to the infection without the influence of host and environment factors. Objective: Determine the associated factors with acute diarrhea in Mexican population with SARS-CoV-2 infection. Methods: A case-control cross-sectional study was performed to analyze the factors associated with acute diarrhea in patients with SARS-CoV-2. This research was carried out during the 2020-2021 in five states of Mexico. An online survey was applied to 784 patients, selected by randomized sampling of whom sociodemographic data, medical history, and symptoms related to SARSCoV- 2 infection were collected. A univariate and multivariate logistic regression analysis was performed applying a χ2 test with 95% confidence intervals to determinate the association of acute diarrhea in SARS-CoV-2 infection with other symptomatology and possible nonhost contributing factors for its presentation. Results: A total of 784 patients were analyzed with a mean age of 29 ± 8 years, predominantly female with 75.4% (591). The most frequently described symptom was fatigue in 75% (588) followed by anosmia and myalgias with 67% (525) and 65.5% (514) respectively. Acute diarrhea was present in 28.6% (321) of our population during the acute phase of SARS-CoV-2 infection. The most used drugs were acetaminophen (79.2%) and azithromycin (29.7%). The multivariate logistic regression analysis showed a statistically significant association between acute diarrhea and the use of macrolides, mainly with clarithromycin with an OR of 2.96 (95% CI of 1.26-6.95, p = 0.001) followed by azithromycin with an OR of 1.47 (95% CI 1.035-2.091, p = 0.031). In this same analysis, there was no significant association of acute diarrhea with the rest of SARS-CoV-2 infection symptoms. Discussion: This study demonstrates the association of acute diarrhea in SARS-CoV-2 infection with the concomitant use of macrolides, without finding any association with described SARS-CoV-2 viral symptoms. According to the previously mentioned, we propose that a proportion of acute diarrhea associated with SARSCoV- 2 infection may be secondary to inappropriate macrolide prescription and not due to the viral disease itself.

10.
Gastroenterology ; 162(7):S-364, 2022.
Article in English | EMBASE | ID: covidwho-1967299

ABSTRACT

Background: Diarrhea is present in up to 36.6% of patients with COVID-19. The mechanism of SARS-CoV-2-induced diarrhea remains unclear. We hypothesized that enterocyte-enteric neuron interactions were important in SARS-CoV-2-induced diarrhea. SARS-CoV-2 induces endoplasmic reticulum (ER) stress in enterocytes causing the release of Damage Associated Molecular Patterns (DAMPs). The DAMPs then stimulate the release of enteric neurotransmitters that disrupt gut electrolyte homeostasis. The influence of ER stress and enteric neuronderived vasoactive intestinal peptide (VIP) on the expression of Na+/H+ exchanger 3 (NHE3), an important transporter that mediates intestinal Na+/fluid absorption, was further examined. Methods: SARS-CoV-2 propagated in Vero-E6 cells was used to infect Caco-2, a human colon epithelial cell line that expresses SARS-CoV-2 entry receptor ACE2. The expression of ER stress markers, phospho-PERK, Xbp1s, and DAMP proteins, was examined by Western blotting. Primary mouse enteric neurons were treated with a conditioned medium of Caco- 2 cells that were infected with SARS-CoV-2 or treated with tunicamycin. VIP expression by cultured enteric neurons was assessed by RT-qPCR, Western blotting, and ELISA. Membrane expression of NHE3 was determined by surface biotinylation. Results: SARS-CoV-2 infection of Caco-2 cells led to increased expression of phospho-PERK and Xbp1s indicating increased ER stress. Infected Caco-2 cells secreted DAMP proteins, including HSP70 and calreticulin, as revealed by proteomic and Western analyses. The expression of VIP mRNA in enteric neurons was up-regulated after treatment with a conditioned medium of SARS-CoV-2- infected Caco-2 cells (Mock, 1 ± 0.0885;and SARS-CoV-2, 1.351 ± 0.020, P=.005). CD91, a receptor for HSP70 and calreticulin, is abundantly expressed in cultured mouse and human enteric neurons and was up-regulated by a conditioned medium of SARS-CoV-2-infected Caco-2 cells. Tunicamycin, an inducer of ER stress, also induced the secretion of HSP70 and calreticulin, mimicking SARS-CoV-2 infection. Moreover, co-culture of enteric neurons with tunicamycin-treated Caco-2 cells stimulated VIP production as determined by ELISA. Co-treatment of Caco-2 cells with tunicamycin (apical) and VIP (basolateral) induced a synergistic decrease in the membrane expression of NHE3. Conclusions: Our findings demonstrate that SARS-CoV-2 infection of enterocytes leads to ER stress and the release of DAMPs that up-regulate the expression and release of VIP by enteric neurons. The presence of ER stress together with the secreted VIP, in turn, inhibits fluid absorption through the downregulation of brush-border membrane expression of NHE3 in the enterocytes. These data highlight epithelial-neuronal crosstalk in COVID-19 related diarrhea. (Figure Presented)

11.
Gastroenterology ; 162(7):S-291-S-292, 2022.
Article in English | EMBASE | ID: covidwho-1967287

ABSTRACT

Background: Post-COVID-19 conditions are defined as new, recurring, or ongoing health issues which present weeks after SARS-CoV-2 infection. The gastrointestinal (GI) involvement of COVID-19 suggests that a group of patients with lingering GI symptoms may develop Post-COVID-19 DGBI including irritable bowel syndrome (IBS) (Schmulson M et al. Am J Gastroenterol. 2021;116:4-7). In this study, we aimed to determine the epidemiological features of Post-COVID-19 DGBI. Methods: Subjects with confirmed COVID-19 at least 6 months before the study who had sustained GI symptoms were invited to complete an internet-based survey on Qualtrics, between March and August 2021. The survey included demographics, acute symptoms, comorbidities, as well as Rome IV questionnaire, Generalized Anxiety Disorder questionnaire (GAD-7) and Patient Health Questionnaire (PHQ)-9 for depression. Data was analyzed using ANOVA and multivariate analysis. Findings were reported as percentage or [p-value;(95% odds ratio CI)]. Results: Overall, 164 subjects (70% female, 14% male, and others unknown) with a positive COVID-19 test completed the survey. Among them, 4% were >65 years old and 24% reported hospitalization. Body mass index ³30 was present in 38%, diabetes in 6.7%, and vitamin D deficiency in 11% of the participants. In total, 108 (66%) subjects fulfilled Rome IV criteria for at least one DGBI. Of 108 with DGBI, only 27 (25%) had DGBI before COVID-19;DGBI developed in 81 subjects after COVID-19. The most common Post-COVID-19 DGBI were functional dyspepsia observed in 38 (postprandial distress syndrome n=31, epigastric pain syndrome n=22) followed by IBS in 26 subjects (IBS with Diarrhea n=7, IBS with Constipation n=4, Mixed-IBS n=14, Unsubtyped IBS n=1) (Table-1). The risk factors of severe COVID-19 including age >65, diabetes, and obesity were not associated with developing Post-COVID- 19 DGBI. Seventy (86%) of subjects with Post-COVID-19 DGBI had at least one GI symptom (abdominal pain, nausea/vomiting, and/or diarrhea) in the acute phase of COVID-19. Nausea/ vomiting during the acute illness increased [p-value of 0.02 with 95% OR CI (0.7-10.4)], and BMI less than 25 also increased the odds [p-value of 0.03 (95% OR CI: 0.26-8.4)] for Post-COVID-19 IBS. Anxiety was present in 48% and depression in 65% of subjects with Post-COVID-19 DGBI. Conclusions: Post-COVID-19 DGBI are new entities associated with a high rate of anxiety and depression. Although the majority of those with Post-COVID-19 DGBI reported having GI symptoms in the acute illness, some appeared in subjects without acute GI symptoms. (Table Presented)

12.
Gastroenterology ; 162(7):S-288-S-289, 2022.
Article in English | EMBASE | ID: covidwho-1967279

ABSTRACT

Background/Aims: COVID-19 infection can affect nearly every organ system including the gastrointestinal (GI) tract. GI symptoms such as nausea, pain and diarrhea are common and may be due to infection and/or increased stress and isolation from the pandemic. It is well known that stress affects GI function and sensation, particularly in patients with irritable bowel syndrome (IBS). The aim of the study was to elucidate the impact of the COVID-19 pandemic on GI symptoms. Methods: An international online survey (Alchemer) was available via the International Foundation of GI Disorders (IFFGD) website from August 11, 2021- November 17, 2021. There were 57 questions exploring demographics, GI symptom/disorder classification, care delivery, administration and perceptions of COVID-19 vaccination, and health experiences during the pandemic. No compensation was provided for survey completion and patients were able to selectively answer questions, with some questions not analyzed for this report. Results: Survey data was included from 210 patients with GI symptoms (mean age 47.7 yrs, 83% female, 80% Caucasian). Participants' primary GI conditions included 36% IBS, 26% gastroparesis, 6% constipation, and 9% acid reflux (figure 1). Seventy percent reported the pandemic impacted their GI health and nearly 3 out of 4 (73%) reported increased pandemic-related anxiety or depression. COVID-19 was diagnosed in 40 (19%) participants. Nearly 3 out of 4 (74%) experienced new or worsening GI symptoms after a COVID-19 diagnosis. Almost a third (30%) with COVID-19 were diagnosed with post-infection (PI) IBS and 38% were diagnosed with a new GI disorder other than PI-IBS. New GI diagnoses after COVID-19 included gastroparesis (53%), GERD (13%), and diarrhea (7%) (figure 2). Prior to diagnosis of PI-IBS, 58% did not have a GI diagnosis. Almost half (46%) of patients reported new acid reflux symptoms after COVID-19. Almost 3 out of 4 patients (72%) with COVID-19 noticed changes in digestion and/or bowel movements. More than two thirds (67%) noted COVID-related GI symptoms lasted >3 months. Nearly 3 out of 4 (72%) patients felt their GI symptoms were harder to manage after COVID-19. Conclusions: Our results highlight the significant burden of GI illness imposed by the COVID-19 pandemic. COVID-19 exacerbated existing GI conditions, increased anxiety and depression, and led to a wide range of new GI issues, led by but not limited to PI-IBS. New diagnoses of upper GI disorders including gastroparesis and GERD were surprisingly common. Further prospective studies to validate these observations and understand their pathogenesis are warranted. (Figure Presented) Figure 1: Participants primary gastrointestinal condition or disorder prior to the COVID- 19 pandemic. (Figure Presented) Figure 2: New GI disorders diagnosed after being diagnosed with COVID-19

13.
Gastroenterology ; 162(7):S-285, 2022.
Article in English | EMBASE | ID: covidwho-1967273

ABSTRACT

SARS-CoV-2 shedding in feces has been reported. We aimed to find: (1)The predictors of fecal viral shedding, (2)Incidence of post-infectious FGIDs in patients with COVID-19 infection. Methods: 188 COVID-19 patients admitted from March to July 2020 were included and prospectively collected the stool samples on admission date and then weekly until negative results. We recorded the clinical and laboratory profiles to find the predictors of fecal viral shedding. Baseline GI symptoms before COVID-19 infection were also evaluated. After discharged, patients were followed regarding their GI symptoms by telephone interviews at 3 and 9 months to evaluate the incidence of post COVID-19 irritable bowel syndrome (IBS), functional constipation (FC), and functional dyspepsia (FD) by using Rome IV criteria. Results: 127 of 188 patients completed stool collection protocol, 85 patients (66.9%) had positive stool SARS-CoV-2 with a duration of viral shedding of 79 (76-90) days. Disease severity, presence of pneumonia, fever, respiratory symptoms, vomiting, and diarrhea were not significantly different between patients with and without fecal viral shedding. Patients with stool shedding had higher prevalence of anosmia [5(83.3%) vs 0, p=0.048], lower absolute lymphocyte [1.42(0.96-1.77) x109/L vs 1.84(1.27-2.17) x109/L, p=0.004], higher ALT [27(18.25-36.75) U/L vs 19(13-28.5) U/L, p=0.02] and lower cycle threshold values [19.68 (16.35-26.40) vs 26.28 (19.34-33.31), p=0.05] (table1). Multivariate analysis including age, diabetes, diarrhea, hemoglobin, absolute lymphocyte, platelet count, ALT, and cycle threshold values demonstrated that there was no factor associated with viral shedding in the stool. 84 patients (44.7%) responsed to the follow-up phone call at 9 months. 3 patients (3.6%) had new onset of GI symptoms during 9-month post COVID-19 infection [early satiety (n=1), diarrhea (n=1), constipation (n=2) and abdominal pain (n=2) with mean severity (SD):8.5 (0.5)of 10]. One patient (1.2%) had FD, No IBS was diagnosed. Conclusions: More than a half of COVID-19 patients had viral shedding in stool for up to 3 months. Univariate analysis demonstrated that low blood lymphocyte and lower cycle threshold values were associated with fecal viral shedding but not the GI symptoms during admission. However, multivariate analysis demonstrated that these factors were not associated with fecal viral shedding. Post-infectious functional GI disorders were uncommon. (Table Presented)

14.
Gastroenterology ; 162(7):S-279, 2022.
Article in English | EMBASE | ID: covidwho-1967268

ABSTRACT

Background and Aims: Initial reports on US COVID-19 showed different outcomes in different races. In this study, we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality. Methods: We analyzed data from hospitalized COVID- 19 patients (n=5,852) from 8 hospitals. Demographics, comorbidities, symptoms and laboratory data were collected. Results: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and dead patients' mean ages were 58 and 68 for AA, 58 and 77 for EA, 44 and 61 for LAT, and 51 and 63 for AS. Mortality rates for AA, LAT, and EA were 14.8%, 7.3%, and 16.3%. Mortality increased among patients with the following characteristics: age, male gender, New York region, cardiac disease, COPD, diabetes mellitus, hypertension, history of cancer, immunosuppression, elevated lymphocytes, CRP, ferritin, D-Dimer, creatinine, troponin, and procalcitonin. Use of mechanical ventilation, respiratory failure, shortness of breath (SOB) (p<0.01), fatigue (p=0.04), diarrhea (p=0.02), and increased AST (p<0.01), significantly correlated with death in multivariate analysis. Male sex and EA and AA race/ethnicity had a higher frequency of death. Diarrhea was among the most common GI symptom amongst AAs (6.8%). When adjusting for comorbidities, significant variables were age (over 45 years old), male sex, EA, patients hospitalized in Indiana, Michigan, Georgia, and District of Columbia. When adjusting for disease severity, significant variables were age over 65 years old, male sex, EA as well as having SOB, elevated CRP, and D-dimer. Glucocorticoid usage was associated with an increased risk of COVID- 19 death in our cohort. Conclusion: Among this large cohort of hospitalized COVID-19 patients enriched for African Americans, predictors of mortality include male gender, diarrhea, elevated AST, comorbidities, respiratory symptoms and failure, and elevation of inflammatory- related biomarkers. These findings may reflect the extent of systemic organ involvement by SARS-CoV-2 and subsequent progression to multi-system organ failure. High mortality in AA in comparison with LAT is likely related to a high frequency of comorbidities and older age among AA.

15.
Gastroenterology ; 162(7):S-171, 2022.
Article in English | EMBASE | ID: covidwho-1967254

ABSTRACT

Background. Malnutrition has been linked to longer hospital stays and adverse health economic outcomes. In COVID-19, there is a paucity of data on whether malnutrition is associated with adverse outcomes in the hospital setting. Methods. This is a retrospective cohort study consisting of 4,311 COVID-19 adult (18 years and older) inpatients at five Johns Hopkins affiliated hospitals between March 1, 2020, and December 3, 2020. Patient data were derived from their COVID-19 database JH-CROWN: The COVID-19 Precision Medicine Analytics Platform (PMAP) Registry and extracted using Python 3, version 3.7.5, kernel in JupyterLab, version 1.1.4. Malnourishment among patients was identified as those who were malnutrition nutrition risk screen positive upon admission by use of the malnutrition universal screening tool (MUST) and confirmed by registered dietitians, Statistics were conducted with SAS v9.4 (Cary, NC) software to examine the effect of malnutrition on mortality and hospital length of stay among COVID-19 inpatient encounters while accounting for possible covariates in linear regression analysis predicting log-transformed length of stay. Results. COVID-19 patients who are older, male, or have lower BMIs have a higher likelihood of mortality (Table 1). In the linear regression model, for every 1% increase in BMI, the length of stay decreased by 0.38% (p<0.001) (Table 2). Differences in race (p=0.001) (Table 1), were associated with differences in the likelihood of mortality and length of stay;being Asian (p=0.0029), Black (p<0.001), or Other (p<0.001) were associated with decreased length of stay compared to Whites (Table 2). Patients with diabetes, hypertension, diarrhea, COPD, and malnutrition were more likely to have higher mortality (p<0.001) (Table 1) and more likely to have a longer hospital length of stay (p<0.001) (Table 2). Overall, 12.9% (555/4,311) of adult COVID-19 patients were diagnosed with malnutrition and were associated with an 87.9% (p<0.001) (Table 2) increase in hospital length of stay. Differences in the source of admission to the hospital affected the likelihood of mortality (p<0.001) (Table 1) and length of stay (Table 2). Conclusions. In a cohort of COVID-19 adult inpatients, malnutrition was associated with a higher likelihood of mortality and increased hospital length of stay. In the linear regression model, malnutrition was associated with an increase in the length of stay by 87.9%. Interestingly, decreases in BMI were associated with increased hospital length of stay. Race and admission source also plays a key role in affecting a patient's hospital length of stay and mortality. These results support the idea that malnutrition appears to be a predictor for COVID-19 inpatient outcomes similar to that of other known highrisk comorbidities like diabetes, hypertension, and COPD.(Table Presented)(Table Presented)

16.
Clinical Epidemiology and Global Health ; 16, 2022.
Article in English | EMBASE | ID: covidwho-1966420
17.
Era's Journal of Medical Research ; 8(2):185-189, 2021.
Article in English | ProQuest Central | ID: covidwho-1964967

ABSTRACT

In China and India, Nelumbo nucífera, a perennial aquatic plant, has been used as a medicinal herb. The various sections of plants, such as leaves, seeds, flowers and rhizomes, have been reported to have beneficial effects in the treatment of pharyngopathy, pectoralgia, spermatorrhoea, leucoderma, smallpox, dysentery, cough, haematemesis, epistaxis, haemoptysis, haematuria, metrorrhagia, hyperlipidaemia, fever, cholera, hepatopathy and hyperdipsia in the traditional medicine system. Different pharmacological activities such as anti-ischaemic activity, antioxidant activity, hepatoprotective activity, anti-inflammatory activity, anti-fertility activity, antiarrhythmic activity, anti-fibrosis activity, antiviral activity, anti-proliferative activity, anti-diarrhoeal activity, psychopharmacological activity, antipyretic activity, immune-modulatory activity, hypoglycaemic activity, aldose reductase inhibitory activity, antibacterial, aphrodisiac activity, anti-platelet activity, cardiovascular activity, anti-obesity activity, lipolytic activity, hypo-cholesterolaemic activity, hepato-protective activity, anticancer activitydiuretic activity, antioxidant activity have been clinically evaluated for N.nucifera. Different pharmacological activities such as anti-ischaemic activity, antioxidant activity, hepato-protective activity, anti-inflammatory activity, anti-fertility activity, anti-arrhythmic activity, antifibrosis activity, antiviral activity, anti-proliferative activity, anti-diarrhoeal activity, psychopharmacological activity, diuretic activity, antioxidant activity have been clinically evaluated for N.nucifera. A wide number of phytoprinciples from the plant have been isolated. The present review seeks to consolidate the traditional, ethno-botanical, phytochemical and pharmacological data available on N.nucifera stem and to explore its role as an immunity booster and anti-inflammatory food.

18.
Acta Agriculturae Jiangxi ; 34(2):160-165, 2022.
Article in Chinese | CAB Abstracts | ID: covidwho-1964892

ABSTRACT

In this study, 650 tissue samples which were collected from 16 pig farms in Hubei Province, were used to detect porcine circovirus (PCV) and Porcine epidemic diarrhea virus (PEDV). The results showed that the positive rates of PCV1, PCV2, PCV3 and PEDV single infection were 1.08%, 4.15%, 2.46% and 6.46%, respectively. In the double infections, PEDV+PCV2 had the highest positive rate of 3.54%, followed by PCV2+PCV3, with a positive rate of 1.54%. In multiple infections, PEDV+PCV2+PCV3 had the highest positive rate of 2.00%. The results indicated that the positive rates of PEDV and PCV were decreased compared with the previous studies, but the prevalence of PEDV and PCV was still wide in Hubei Province, and most of which were co-infection.

19.
Journal of Yangzhou University, Agricultural and Life Sciences Edition ; 42(6):48-53, 2021.
Article in English, Chinese | CAB Abstracts | ID: covidwho-1964809

ABSTRACT

As a member of the family Picornaviridae, porcine sapelovirus (PSV) is often infected with porcine epidemic diarrhea virus, teschovirus and so on. In recent years, PSV has been isolated from porcine in many provinces of China. It suggests that it is necessary to strengthen the research on PSV. In this study, according to the sequence of PSV HuN2 strain, VP1 gene was inserted into the pGEX-6 P-1 vector, and expressed the recombinant protein. BALB/c mice aged 6-8 weeks were immunized according to the standard procedure. After the third immunization, the mouse orbital blood was collected to identify the antibody level. The highly positive mouse spleen cells were selected for cell fusion. The positive hybridoma cells and two subclones were screened by IFA method, and then a PSV VP1 monoclonal antibody was obtained, named as 33-2 A. The results of IFA showed that PSV could be recognized by 33-2 A MAb, and specific green fluorescence appeared in the cytoplasm;The results of WB and IP showed that PSV infected porcine cell could specifically bind to 33-2 A, and there was a specific band at 32 ku. We also identified the B-cell antigen epitope of 33-2 A, it was at amino acids 40-46 of PSV VP1 protein, and the polypeptide sequence was 40PALTAAE46. The results showed that the monoclonal antibody can react with PSV VP1 protein. The epitope was analyzed with the PSV sequences uploaded in NCBI, 33-2 A antibody can react with most PSV strains and has a certain universal to PSV. This study laid a foundation for the study of the etiology and pathogenesis of PSV.

20.
Animal Husbandry and Feed Science ; 43(4):14-18, 2022.
Article in Chinese | CAB Abstracts | ID: covidwho-1964618

ABSTRACT

[Objective] To identify the B-cell epitope peptide of porcine epidemic diarrhea virus (PEDV) S2 gene by combinative use of bioinformatics software and monoclonal antibody technology. [Method] The B-cell epitope of PEDV S2 gene was screened using CLC Sequence viewer 6.8 software and IEDB online database, and the obtained epitope peptide was synthesized artificially. Female BALB/c mice were immunized with the conjugate of epitope peptide and keyhole hemocyanin (KLH) as antigen. Mice with higher antibody titers were identified by ELISA assay and then received an additional immunization. The spleen of the mice was taken 3 days post immunization to prepare the splenocyte suspension for cell fusion. The cells were grown on HAT selective medium to screen for effective hybridoma cells. The positive clones screened by ELISA assay were then used for expanding culture. Positive hybridoma cells were intraperitoneally injected to mice and ascites were collected. ELISA assay was used to determine the antibody titers in mice ascites and in the supernatants of monoclonal cell strains. The cells with the highest antibody titers was used as cell strain for subsequent use. [Result] The selected B-cell epitope peptide sequence was MQYVYTPTYYML Following immunization with the peptide antigen, the serum antibody titer before cell fusion reached 1:2 000. The ELISA assay of ascites from BALB/c mice and the supernatants from monoclonal cell strain cultures demostrated that the antibody liter reached 1:4 000. [Conclusion] The B-ell epitope of PEDV S2 gene was identified, which may be helpful for the vector construction of a epitope based peptide vaccine against PEDV.

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