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1.
Open Forum Infectious Diseases ; 8(SUPPL 1):S453, 2021.
Article in English | EMBASE | ID: covidwho-1746390

ABSTRACT

Background. Clostridiodes difficile infection (CDI) is common and classified as an urgent threat by the US Centers for Disease Control and Prevention. Recurrence (rCDI) occurs in 30% of cases and increases with subsequent episodes. As part of a trial of fecal microbiota transplantation vs. placebo for the prevention of rCDI, rCDI is identified using a case-finding algorithm that screens for potential cases across all Veterans Affairs facilities, a key component of which is a stool test confirming the presence of C. difficile. With the emergence of Covid-19 in the Unites States in early 2020, study personnel observed a decreasing number of rCDI cases. We hypothesized that Covid restrictions and fear of transmission prevented patients from coming to a VA facility to submit a confirmatory stool sample, the standard method of diagnosing rCDI. Accordingly, the algorithm was modified to also identify cases where rCDI was empirically treated, without confirmatory testing. Here we report on the prevalence of empiric treatment of rCDI during the Covid pandemic and changes in lab-conformed cases over time. Methods. Cases of potentially rCDI are identified by a weekly query of VA data, using an algorithm that includes laboratory testing results, diagnostic codes, and prescriptions. The ource database is updated daily from every VA facility, encompassing over 8 million Veterans. Potential cases are reviewed by research coordinators using the medical record to determine study eligibility. Beginning June 2020, the algorithm was adjusted to also identify patients with lab confirmation of their first CDI episode but none for their recurrence and identified those who were prescribed treatment for rCDI. Results. We observed a reduction in both the number of weekly cases (22.2 vs. 17.4;P < 0.001) which is a 22% decrease after the Covid-19 emergency declaration (figure). Post-declaration, empiric treatment was prescribed to 159 Veterans (mean, 3.3/week). Potential cases of rCDI/week pre- and post Covid-19 pandemic declaration Conclusion. There was a significant drop in laboratory-confirmed rCDI associated with Covid-19. Recurrent CDI was frequently empirically treated during the Covid-19 pandemic, potentially exposing many patients with non-CDI diarrhea to unnecessary antimicrobial use and its attendant risks.

2.
Gastroenterology ; 160(6):S-233-S-234, 2021.
Article in English | EMBASE | ID: covidwho-1594011

ABSTRACT

Background: Up to 36.6% of COVID-19 patients have diarrheal symptoms and 48.1% test positive for SARS-CoV-2 via stool test. The mechanism of SARS-CoV-2-associated diarrhea remains poorly understood. We hypothesize that crosstalk between enterocytes and the enteric nervous system (ENS) plays a critical role in the pathogenesis of COVID-19-associated diarrhea. We studied the effects of SARS-CoV-2 on induction of endoplasmic reticulum (ER) stress and release of Damage Associated Molecular Patterns (DAMPs), which act on enteric neurons and stimulate the production of neurotransmitters. The influence of ER stress and enteric neuron-derived vasoactive intestinal peptide (VIP) on the expression of electrolyte transporter Na+/H+ exchanger 3 (NHE3) was also examined. Methods: SARS-CoV-2 (2019-nCoV/USA-WA1/2020) was propagated in Vero-E6 cells. Caco-2, a human colon epithelial cell line, expresses the essential SARS-CoV-2 entry receptor ACE2 and was thus used for infection (MOI, ~0.01). We used Western blotting to assess the expression of ER stress (phospho-PERK and Xbp1s) and DAMP (HMGB1) markers at 48 hours post-infection. Primary mouse enteric neurons were co-cultured with Caco-2 cells, pre-treated for 24 hours with 2 μM tunicamycin to induce ER stress. Supernatants from enteric neurons were used to assess the expression of VIP by ELISA. Primary enteric neurons were treated with HMGB1 or ATP (another form of DAMPs), and the expression of c-FOS, a marker of neuronal activity, was determined by Western blotting and immunofluorescence staining. Results: We found that SARS-CoV-2 infection of Caco-2 cells led to increased expression of phospho-PERK and Xbp1s. Compared to uninfected control, infected Caco-2 cells secreted HMGB1 into culture media, indicating epithelial production of DAMPs in response to SARS-CoV-2 infection. Tunicamycin was used to induce ER-stress and secretion of HMGB1 by Caco-2, mimicking SARS-CoV-2 infection. Importantly, enteric neurons co-cultured with tunicamycin-treated Caco-2 cells secreted significantly higher levels of VIP. Treating Caco-2 cells with tunicamycin or VIP on the basolateral side led to decreased surface NHE3 expression, suggesting a potential impairment of intestinal electrolyte/fluid absorption. More-over, HMGB1 and ATP both increased the expression of phospho-c-FOS in cultured enteric neurons, indicating DAMP-induced neuronal activation. Conclusions: Our findings demon-strate that enterocytes infected by SARS-CoV-2 release DAMPs with the capacity to induce VIP secretion by the enteric neurons, which in turn acts on enterocytes and inhibits apical localization of NHE3. These findings establish basic mechanisms relevant to diarrheal disease in COVID-19 patients and identify potential targets for the treatment of SARS-CoV-2 infection of the gastrointestinal tract.

3.
British Journal of Surgery ; 108(SUPPL 7):vii118, 2021.
Article in English | EMBASE | ID: covidwho-1585079

ABSTRACT

Aim: Early diagnosis and treatment of Colorectal Cancer can improve outcomes. Polypectomy with colonoscopy has failure and incompletion rates with risk of aerosol-generation. Computed Tomographic Colonography, second investigation, is limited by radiation exposure and aerosol generation. Colon Capsule endoscopy is a novel technique without gas insufflation, therefore avoiding the discomfort and aerosol- generation. Our aim is to compare the yield of the CCE with CTC in CRC and polyps in patients with positive stool tests or diagnosed colorectal lesions. Methods: Review followed PRISMA standards. Electronic database (EMBASE, MEDLINE, PubMed, CINAHL) searched for RCTs and Observational studies. MedCalc Statistical Software used for the synthesis of results. Primary (Per-Lesion and Per-Patient sensitivity analysis) and secondary (Other lesion and completion rate sensitivity analysis) outcomes measured using a random-effect model. Results: We found one RCT and three observational studies. Per-Lesion Sensitivity Analysis of CCE versus CTC showed overall effect of 1.903 (0.990- 1.937), p-value-0.057. Per-Patient Sensitivity Analysis of showed overall effect of 1.928 (0.995-1.892), p-value-0.054. Other lesions Sensitivity Analysis showed overall effect of 0.810 (0.121-161.995), pvalue- 0.418. Completion Rate Sensitivity Analysis showed overall effect of -0.419 (0.526-1.516), p-value-0.676. Conclusion: CCE had a better detection rate for colorectal cancer and polyp than the CTC, but this was not statistically significant. Therefore, this study failed to prove CCE's superiority over CTC. A careful decision can be made in current COVID-19 pandemic since its advantage of zero aerosolisation. Researchers should focus on innovation in techniques and simultaneous high-quality studies to evaluate them.

4.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):468-469, 2021.
Article in English | EMBASE | ID: covidwho-1570395

ABSTRACT

In 2012 a 25-year-old man presented to our outpatient clinic for severe atopic dermatitis (AD) and severe allergic eosinophilic asthma in polisensitivity (house dust mite, cat, gramineous plants, birch, milk protein and, in particular, Alternaria). His clinical history was also characterized by gastro-esophageal reflux disease and chronic rhinitis without polyposis, with septal deviation and turbinate hypertrophy, worthy of surgical intervention. History taking revealed egg and cow milk protein allergy and severe asthma since the first months of life, with frequent hospital admissions due to exacerbations. AD was severe and diffuse, involving especially face, neck, back and superior limbs, often complicated by impetigo. The esthetic, social and psychological impact led him to quit his job as a barman. At presentation, the Eczema Area and Severity Index (EASI) score was 72/72. Laboratory tests showed eosinophilic count ranging between 1.060 and 2.140/mm3, and high serum levels of total Immunoglobulin E (5.939 kUI/L). Tryptase levels were normal and autoantibody analysis was negative. Parasite stool examination was negative. Nasal swab tested positive for Staphylococcus aureus, which was treated with Sulfamethoxazole-Trimethoprim. Asthma Control Test was 15/25, pulmonary function tests (PFTs) showed mild obstruction (FEV1 4.43 L, 103%, FEV1/FVC 69%), with positive bronchodilator testing (FEV1 5.12 L, + 670 mL, + 16%). Firstly, he was treated with topical steroids and sometimes with oral corticosteroids, with poor response. Then, in July 2019, he initiated therapy with cyclosporine 3-5 mg/kg. Soon, the drug had to be discontinued due to adverse effects (gastrointestinal symptoms and infections). In November 2019, at the age of 32 years, he started therapy with monoclonal antibody anti-IL-5 receptor alpha (benralizumab 30 mg 1 subcutaneous vial every 4 weeks for the first three administrations and then every 8 weeks), with a terrific clinical improvement of AD since the first administrations and with benefit on asthma control (ACT after the first administration increased up to 25/25;PFTs could not be performed, due to SARS-CoV-2 pandemic). This therapy has always been well tolerated. The eosinophilic count decreased to 0/mm3 after the first administration. At the moment, after one year of therapy, AD is almost fully disappeared (EASI SCORE 4/72), despite being in free diet, and the quality of life of the patient has definitely improved.

5.
American Journal of Translational Research ; 13(11):12875-12886, 2021.
Article in English | EMBASE | ID: covidwho-1567794

ABSTRACT

Objective: To explore the risk factors for early clinical recurrence of inflammatory bowel disease (IBD) after fecal microbiota transplantation (FMT). Methods: A retrospective study was conducted on 192 patients with IBD who received FMT treatment in the Colorectal Disease Specialty/Intestinal Microecology Treatment Center of the Tenth People’s Hospital Affiliated to Tongji University from February 2017 to June 2020. Univariate and multivariate logistic regression models were used to analyze the risk factors for early recurrence of inflammation. Feces from all participants were collected to extract the total bacterial genomic DNA. The V6-8 regions of the bacterial 16S rDNA gene were amplified by polymerase chain reaction (PCR), the PCR products were detected by the denaturing gradient gel electrophoresis (DGGE) method, and the intestinal flora was analyzed by DNA fingerprinting. Stool samples from all patients were tested for 9 bacteria, white blood cells (WBC) and platelet (PLT) counts, as well as the erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) level. Results: Of the 192 patients, 15 cases had inflammation recurrence during FMT and within one week after treatment, including 11 cases of ulcerative colitis (UC) and 4 cases of Crohn’s disease (CD), with a total recurrence rate of 7.8%. High Mayo inflammatory activity score, Mayo endoscopic sub-item score (MES) =3 points, CRP>10 mg/L, anemia, albumin <30 g/L, absolute value of peripheral blood lymphocytes (PBL) <500/mm3, and intolerance to enteral full nutrition were independent risk factors for recurrence during and after FMT in UC patients (P<0.05). Albumin <30 g/L and simultaneous use of immunosuppressive agents were associated with disease recurrence during and after FMT in CD patients. WBC, PLT, and CRP were all negatively correlated with Enterococcus (EC), and ESR was positively correlated with Saccharomyces boulardii (SB) (P<0.01). Conclusion: The low recurrence rate of IBD after FMT indicates the safety of FMT, but this procedure should be cautiously used in patients with severe intestinal barrier dysfunction and/or severe intestinal dysfunction.

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