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Introduction: Multiple meta-analyses have shown that over 15% patients with COVID-19 have at least one gastrointestinal complaint, most commonly diarrhea. The effects on the gastrointestinal system are thought to be mediated by the high expression of angiotensin-converting enzyme 2 (ACE2) and cellular serine proteases (TMPRSS2) in enterocytes, which cause altered intestinal permeability. The purpose of this study was to determine the incidence of diarrhea as it relates to COVID-19 infection and to determine if having concomitant diarrhea had a significant impact on disease course. Method(s): A retrospective chart review of 164,730 patients in a hospital system who were older than 18 years of age and had a positive SARS-CoV-2 test from March 2020 to February 2022 was completed. Diarrhea was determined using ICD code or patient's symptoms. Patients with confounding variables such as IBD, IBS, Celiac, Clostridium difficile, and pancreatic insufficiency were excluded. Demographic clinical characteristics and outcomes, including inpatient admission and mortality, were compared in patients with and without diarrhea. The Mann-Whitney test and Fisher's exact or Chi-square test was used for continuous and categorical variables respectively and multivariate logistic regression was used to evaluate for significant differences in disease outcome between the two groups. (Table) Results: Of the 164,730 patients included, 14,648 (8.89%) had diarrhea at the time of SARS-CoV-2. 6,748/33,464 (20.16%) of inpatient admissions were associated with diarrhea. On multivariate analysis, diarrhea was an independent risk factor for inpatient hospitalization (OR 2.39, CI 95% 2.28-2.51, P, 0.001) and inpatient mortality (OR 1.15, CI 96% 1.06-1.26, P= 0.001) after controlling for age, gender, race, comorbidities that could impact patient outcome, use of immunomodulators and outpatient antibiotics. Conclusion(s): These findings show that, even with controlling for comorbidities with COVID-19, diarrhea was an independent factor for predicting inpatient mortality and inpatient admission in general. Patients who had diarrhea and COVID-19 were sicker, having more comorbid conditions than those without diarrhea in our cohort. Attention should be given to not only respiratory complaints of COVID-19, but also gastrointestinal complaints, as they are an indicator of poor prognosis and mortality.
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The Coronaviridae family's severe acute respiratory syndrome corona virus 2 (SARS-Co V-2) outbreak has infected a large number of the population during the COVID- 19 pandemic. The most prominent mode of virus transmission is considered through respiratory droplets of the infected person. Virus-mediated respiratory infection depends upon the binding between spike protein and the Angiotensinconverting enzyme 2 (ACE2) receptor expressed in lung alveolar type 2 cells. But some studies reported that gastrointestinal infection is also one of the prominent symptoms of COVID-19 because of the high expression of the ACE2 receptor in absorptive enterocytes of the small intestine. In a country like India, with high population density and due to unhygienic sanitation, it is crucial to understand the potential fecal-oral transmission route of SARS-CoV-2 during infection because of presence of ACE2 in small intestine. Therefore in our study, we aim to trace the potential fecal-oral transmission route of SARS-Co V-2 by examining human stool (collected from hospital settings) and nearby sewage water systems, followed by molecular characterization and viral load kinetics evaluation of SARSCOV- 2. qRT-PCR and NGS sequencing methods were used. The presence of SARS-COV-2 was reported in around 70% of samples (both clinical and environmental), this will help us to establish the epidemiological link between clinical and environmental samples after genomic analysis to alter the circulation of silent SARS Co V2 in the community.
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Livestock products supply about 13 percent of energy and 28 percent of protein in diets consumed worldwide. Diarrhea is a leading cause of sickness and death of beef and dairy calves in their first month of life and also affecting adult cattle, resulting in large economic losses and a negative impact on animal welfare. Despite the usual multifactorial origin, viruses are generally involved, being among the most important causes of diarrhea. There are several viruses that have been confirmed as etiological agents (i.e., rotavirus and coronavirus), and some viruses that are not yet confirmed as etiological agents. This review summarizes the viruses that have been detected in the enteric tract of cattle and tries to deepen and gather knowledge about them.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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SESSION TITLE: Extraordinary Cardiovascular Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: The COVID-19 pandemic has reshaped modern history with an estimated death count over 6 million globally. Symptoms are primarily respiratory;however, COVID also confers an increased risk for hypercoagulability with the common presentations of venous and small vessel arterial thrombi (1). Acute mesenteric ischemia (AMI) is rare. We present a case of severe AMI with arterial and venous thrombi related to COVID. CASE PRESENTATION: A 50-year-old non-COVID-vaccinated male with a history of alcohol abuse presented with 1 day of emesis and abdominal pain and was found to be COVID-19 positive without respiratory symptoms. Computed tomography angiogram of the chest, abdomen and pelvis revealed normal lungs, extensive non-calcified thrombi in the abdominal aorta extending into the celiac artery causing severe stenosis, complete occlusion of the superior mesenteric, right portal, and splenic veins, partial occlusion of the extrahepatic portal vein, left lower pulmonary embolism, small bowel perfusion injury, and splenic and right hepatic lobe infarcts. He denied a personal or family history of hypercoagulability. The patient was placed on a heparin drip and underwent placement of a transjugular intrahepatic portosystemic shunt and an infusion catheter for administration of tissue plasminogen activator into the portal vein. He ultimately required a thrombectomy. Later imaging showed patency of previously occluded vessels and resolution of arterial thrombus. Over the course of his hospitalization, his respiratory status did decompensate, and he required 13 days of mechanical ventilation, after which he was extubated, transitioned to warfarin, and discharged. DISCUSSION: AMI in COVID has been identified as a rare but serious complication with a reported incidence of 3-4%, with a reported mortality of up to 47% in all-cause-related AMI(2,3). COVID causes a prothrombotic state due to its affinity to angiotensin-converting enzyme-2(ACE2) receptors on enterocytes and endothelium, allowing it to infect the cells and causing direct damage to bowel tissue and vessels. The binding of ACE2 also increases IL-6, inducing cytokine storm and hypercoagulability (1). While there are no clear guidelines, treatment mainly involves revascularization and removal of necrotic bowel. Anticoagulation generally has favorable results within 48 hours and invasive intervention is not required (1,4). Thus, early recognition of AMI as a potential complication of COVID is essential for early treatment and reduction of the staggering morbidity and mortality. CONCLUSIONS: While the incidence of AMI in COVID is low, it can have severe effects on patients and requires early recognition and treatment. Further studies are needed to develop awareness of the disease, therefore improving surveillance and standard of care to minimize the chances of these poor outcomes. Reference #1: Patel, Suyog et al. "Bowel ischemia in COVID-19: A systematic review.” International journal of clinical practice vol. 75,12 (2021): e14930. doi:10.1111/ijcp.14930 Reference #2: Kaafarani, Haytham M A et al. "Gastrointestinal Complications in Critically Ill Patients With COVID-19.” Annals of surgery vol. 272,2 (2020): e61-e62. doi:10.1097/SLA.0000000000004004 Reference #3: Cudnik, Michael T et al. "The diagnosis of acute mesenteric ischemia: A systematic review and meta-analysis.” Academic emergency medicine : official journal of the Society for Academic Emergency Medicine vol. 20,11 (2013): 1087-100. doi:10.1111/acem.12254 Chen, Can et al. "Acute Mesenteric Ischemia in Patients with COVID-19: Review of the literature.” Journal of the National Medical Association vol. 114,1 (2022): 47-55. doi:10.1016/j.jnma.2021.12.003 DISCLOSURES: No relevant relationships by Mohamed Abdelhabib No relevant relationships by Naomi Habib No relevant relationships by Daniel Rabulinski No relevant relationships by Suresh Uppalapu
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INTRODUCTION: The rate of pediatric patients diagnosed with Sars Cov 2 has increased since the early stages of the pandemic. Gastrointestinal symptoms have been demonstrated to be relatively common in pediatric COVID-19 patients as well as severe complications like PIMS syndrome because of the expression of ACE II in different areas of the digestive tract which serves as a receptor for their entry and infection in the body. During the last months of the omicron variant wave, we observed some gastrointestinal conditions in pediatric patients days after the resolution of the Sars Cov 2 acute infection period, sparking our interest to execute further research and analysis. OBJECTIVE(S): Describe the presence of functional gastrointestinal disorders as a post-covid infection sequel METHODS: We performed a descriptive, cross-sectional, observational, retrospective study, were we recollected the clinical and epidemiological data from the medical records of pediatric patients with a history of Sars cov-2 infection confirmed with positive PCR or antigen (sars cov-2) tests at Hospital Angeles Lomas, Mexico City. We included children from 6 months up to 16 years of age, who presented functional gastrointestinal disorders at a minimum 15 days after the infection that fulfilled Rome IV criteria. We evaluated the frequency and proportion of the qualitative variables;we obtained the arithmetic mean and the standard deviation for the quantitative variables with normal distribution RESULTS: We included data from 30 patients with confirmed covid 19 diseases by positive pcr or antigen (sars cov-2) tests, with a mean age 5.327 +/- 3.8 years Min: 7 months Max: 16 years, with a female predominance of 56.7% vs 43% male patients. During the acute infection by covid, 20% presented respiratory symptoms, 13.3% gastrointestinal symptoms, 36.7% only fever, 3.3% dysgeusia and 26.7% were asymptomatic. Adequate nutritional status was detected in 93% of the patients. The mean days the patients presented manifestations was 32 +/- 14 days, at a minimum 15 days, with a maximum of 63 days, being the most frequent functional gastrointestinal disorders: abdominal pain 90%, bloating 76%, vomit and reflux 33%, diarrhea 30%, constipation 26.7%. There was no weight loss in the patients, the appropriate treatment was given for each case. There was no complication in 90% of the patients, 10% presented acute abdominal pain and were transferred to the emergency room, 1 patient was diagnosed with appendicitis and 2 patients with mesenteric lymphadenitis. CONCLUSION Special attention must be paid to toddler and preschooler patients with Sars Cov 2 infection, regardless of the clinical manifestation in acute infections, mild or asymptomatic, functional gastrointestinal disorders may occur in the first 2 months after a positive PCR test. The ileum and the colon are places in which there is a greater expression of the ACE II, so when the enterocytes are invaded by SARS CoV-2, they may produce alterations in absorption and other mechanisms that could be the cause of these consequences. It is of vital importance that all pediatricians are aware of the consequences of the disease to prevent misdiagnosis.
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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)
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Background: Initial evidence has shown the occasional presence of SARS-CoV-2 in enterocytes in the intestines of patients with COVID-19. Our aim is to further assess the clinical and pathologic changes in the gastrointestinal tract caused by the highly contagious Delta (B.1.617.2) variant as compared to viral variants originating earlier in the pandemic. Design: Intestinal samples from 32 patients with death due to COVID-19 were obtained at autopsy. Decedents were males and females, with an age range of 32-73 years. Twenty-one of the decedents self-identified as Black/African American, eight as Caucasian, and three as Hispanic. Two groups were differentiated by viral genome RNA sequencing from autopsy tissue: those with Delta variant (n=16), and those with non-Delta variant (n=16). SARS-CoV-2 expression in the intestine was evaluated by immunohistochemical (IHC) detection of the SARS-CoV-2 nucleocapsid protein (N-protein). Results: Clinically, the Delta group reported diarrhea more frequently (25%) as compared to the non-Delta group (6%). Patients in the Delta group had a shorter time interval between the onset of gastrointestinal symptoms and death (mean = 19 days), as compared to the non-Delta group (mean = 25 days). Histologic examination revealed mostly normal to mild, non-specific chronic inflammation within the epithelium and lamina propria in both groups. Macrophages with positivity for N-protein IHC were present beneath the epithelium, most notably within the Delta group. N-protein positivity occurred most frequently in small submucosal and mesenteric blood vessels. Patchy positivity for N-protein in enterocytes was seen frequently in cases of Delta variant in which the time from initial symptoms to death was short (<14 days). Figure 1 - 11 Conclusions: As in prior studies, intestinal microscopic changes in COVID-19 were minimal, though our findings indicate that SARS-CoV-2 may be detected within enterocytes more frequently in the Delta group. Patients with the Delta variant experienced both a higher rate of diarrhea and a shorter interval between gastrointestinal symptom onset and death. Whether increased Nprotein in enterocytes is a result of the Delta variant itself, or earlier intestinal sampling relative to symptoms in this group, remains to be determined. Autopsy studies can add to our understanding of the effects of COVID-19 on the digestive system, by allowing a greater volume of tissue sampling, as well as temporal sampling relative to disease onset that is not always possible at endoscopy.
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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.