Postmortem examination of equids >1-year-old with enterotyphlocolitis in Ontario: a retrospective descriptive study.

Equine enterotyphlocolitis is an inflammatory process of the intestinal tract of horses that is associated with multiple etiologic agents and risk factors. Most clinical cases do not have an etiologic diagnosis. We describe here the pathogens detected and the histologic lesions found in horses with enterotyphlocolitis in Ontario that were submitted for postmortem examination, 2007-2019. We reviewed the medical records of 208 horses that fulfilled inclusion criteria. Cultures were positive in 67 of 208 (32%) equids for Clostridium perfringens, in 16 of 208 (8%) for Clostridioides difficile, and in 14 of 208 (7%) for Salmonella spp.; 6 of 208 (3%) were positive for Neorickettsia risticii by PCR assay. One horse was positive in a Rhodococcus equi PCR assay. All horses tested by PCR assay for equine coronavirus and Lawsonia intracellularis were negative. The histologic lesions were characterized as follows: 6 of 208 (3%) enteritis, 5 of 208 (2%) typhlitis, 104 of 208 (50%) colitis, 37 of 208 (18%) enterocolitis, 45 of 208 (22%) typhlocolitis, and 11 of 208 (5%) enterotyphlocolitis. We strongly recommend standardized testing of diarrheic horses during and/or after postmortem examination, as well as standardized reporting of histologic lesions in enterotyphlocolitis cases.

Fatal gastritis and enterocolitis due to concurrent Helicobacter pylori and Campylobacter jejuni infection in a captive cheetah (Acinonyxjubatus).

A 3.5-year-old female cheetah (Acinonyx jubatus) died after a 10-day history of anorexia, regurgitation and diarrhoea despite symptomatic therapy. At gross post-mortem examination, the stomach was blood-filled with mucosal thickening and multifocal ulcerations. The intestinal mucosa was thickened and reddened, and the intestinal lumen was filled with dark red to black pasty content. Gastric histological lesions were compatible with gastritis due to Helicobacter infection, which was confirmed by polymerase chain reaction. Histology of the intestines revealed a severe necrotizing neutrophilic enterocolitis with abundant intralesional curved to spiral bacteria, corresponding to Campylobacter jejuni, which were subsequently isolated from both small and large intestinal contents. No other intestinal pathogens were detected despite thorough investigations. These findings suggest that C. jejuni may have played an aetiological role in the enterocolitis. Such an association has not been previously reported in non-domestic felids.

Epidemiologic and Clinical Features of Campylobacter Enteritis Before and During COVID-19 in Korea.

BACKGROUND: With the increase in meals at home due to coronavirus disease 2019 (COVID-19), the pattern and incidence of enteritis seemed to change. Some types of enteritis, such as Campylobacter enteritis, appear to have increased. Our study aimed to evaluate the change in the trend of enteritis, especially Campylobacter enteritis, before COVID-19 (2016-2019) and at the present time during COVID-19 in South Korea. METHODS: We analyzed data from the Health Insurance Review and Assessment Service. From 2016 to 2020, the International Classification of Diseases codes related to enteritis were examined to distinguish bacterial and viral enteritis and the trends of each were analyzed. The aspects of enteritis, before and after the COVID-19 outbreak, were compared. RESULTS: Both bacterial and viral enteritis declined in all age groups from 2016 to 2020 (P < 0.001). In 2020, the reduction rate of viral enteritis was higher than that of bacterial enteritis. However, unlike other causes of enteritis, even after COVID-19, Campylobacter enteritis increased in all age groups. An increase of Campylobacter enteritis in 2020 was particularly noticeable in children and adolescents. The prevalence of viral and bacterial enteritis was higher in urban areas than in rural areas (P < 0.001). Campylobacter enteritis was more common in the rural areas (P < 0.001). CONCLUSION: Although the prevalence of bacterial and viral enteritis have decreased in COVID-19, Campylobacter enteritis has increased in all age groups and in rural areas compared to urban areas. Recognizing that the trend of Campylobacter enteritis before and during COVID-19 is helpful for future public health measures and interventions.

Neonatal necrotizing enterocolitis due to COVID-19. A case report.

Digestive symptoms have been reported in an important proportion of children with COVID-19, and the clinical expression of critical patients with COVID-19 is thought to result from progressive increase of inflammation and an unusual trend of hypercoagulation. We report a newborn received with abdominal distension, green vomiting and imaging suggestive for enterocolitis. He had a close contact with COVID-19 and the PCR for SARS-CoV-2 came back positive. Despite the supportive measures, his condition deteriorated and a surgery was decided. The surgical exploration found an ischemic bowel. The therapeutic measures were ineffective as the child passed away a few hours after surgery despite the resuscitation treatment performed. The confirmed enterocolitis happening within the period of acute infection by SARS-CoV-2, the NEC was likely a manifestation of COVID-19.

The impact of the COVID-19 pandemic on other infections differs by their route of transmission: A retrospective, observational study in Japan.

INTRODUCTION: The Coronavirus disease 2019 (COVID-19) pandemic and people's subsequent behavioral changes have decreased the cases of respiratory infection worldwide. However, research on infectious diseases with other transmission modes is insufficient. The aim was to assess the impact of the COVID-19 pandemic on non-respiratory infectious diseases: infectious enterocolitis, sexually transmitted diseases such as human immunodeficiency virus (HIV) infection and syphilis, and tick-borne diseases. METHODS: This retrospective, cohort study used comprehensive surveillance data from the National Institute of Infectious Diseases in Japan from January 1, 2018, to December 31, 2021. The number of cases of infectious diseases before the COVID-19 pandemic (2018-2019) was compared with that during the COVID-19 pandemic (2020-2021). Reduction rates were calculated as the number of disease cases during the COVID-19 pandemic in 2020 and 2021, respectively, divided by the mean number of disease cases in 2018 and 2019. RESULTS: The total numbers of cases of infectious enterocolitis, sexually transmitted diseases, and tick-borne diseases during the study period were 2,507,304 cases, 24,972 cases, and 3012 cases, respectively. The number of cases decreased for infectious enterocolitis and sexually transmitted diseases during the COVID-19 pandemic compared with before the COVID-19 pandemic, with an approximately 40-50% decrease in enterocolitis and 30-55% decreases in sexually transmitted diseases. However, cases of tick-borne diseases changed little, with a 0.2% increase in 2020 and a 6% increase in 2021. CONCLUSION: The COVID-19 pandemic had a different impact on the number of cases of infectious diseases depending on their mode of transmission.

Rapid immune perturbations during sepsis and necrotising enterocolitis in preterm babies (preprint)

Deaths complicated by infection are a major cause of mortality in preterm babies. Here we study the influence of bacterial sepsis and the gut inflammatory disorder necrotising enterocolitis (NEC), frequently associated with bacterial complications, on host immune dysregulation in extremely preterm babies. We identify a peripheral blood immune signature that distinguishes sepsis and NEC from other cases of suspected, though microbiologically unconfirmed, sepsis. Some signature traits could even make this distinction in babies with low or undetectable C-reactive protein, a common clinical test to alert infection. Our analysis incorporates longitudinal single-cell genomic evaluation of peripheral blood immune cells, elucidating amphiregulin as a key differentially expressed gene during sepsis and NEC, which was validated as a plasma analyte that correlated with disease-associated clinical signs. Collectively, signature immune traits provide insight into dysregulated sepsis and NEC-associated pathways and highlight candidate markers, pending validation, that could improve diagnostic-led, targeted antibiotic prescribing.

Probiotics for the prevention of Hirschsprung-associated enterocolitis.

BACKGROUND: Hirschsprung-associated enterocolitis (HAEC) is a leading cause of serious morbidity and potential mortality in children with Hirschsprung's disease (HD). People with HAEC suffer from intestinal inflammation, and present with diarrhoea, explosive stools, and abdominal distension. Probiotics are live microorganisms with beneficial health effects, which can optimise gastrointestinal function and gut flora. However, the efficacy and safety of probiotic supplementation in the prevention of HAEC remains unclear. OBJECTIVES: To assess the effects of probiotic supplements used either alone or in combination with pharmacological interventions on the prevention of Hirschsprung-associated enterocolitis. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, the China BioMedical Literature database (CBM), the World Health Organization International Clinical Trials Registry, ClinicalTrials.gov, the Chinese Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, and Clinical Trials Registry-India, from database inception to 27 February 2022. We also searched the reference lists of relevant articles and reviews for any additional trails. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing probiotics and placebo, or any other non-probiotic intervention, for the prevention of HAEC were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of the included studies; disagreements were resolved by discussion with a third review author. We assessed the certainty of evidence using the GRADE approach. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes. MAIN RESULTS: We included two RCTs, with a total of 122 participants. We judged the overall risk of bias as high. We downgraded the evidence due to risk of bias (random sequence generation, allocation concealment, and blinding) and small sample size. The evidence is very uncertain about the effect of probiotics on the occurrence of HAEC (OR 0.58, 95% CI 0.10 to 3.43; I² = 74%; 2 studies, 120 participants; very low-certainty evidence). We found one included study that did not measure serious adverse events and one included study that reported no serious adverse events related to probiotics. Probiotics may result in little to no difference between probiotics and placebo in relation to the severity of children with HAEC at Grade I (OR 0.66, 95% CI 0.14 to 3.16; I² = 25%; 2 studies, 120 participants; low-certainty evidence). The effects of probiotics on the severity of HAEC at Grade II are very uncertain (OR 1.14, 95% CI 0.01 to 136.58; I² = 86%; 2 studies, 120 participants; very low-certainty evidence). Similarly, the evidence suggests that probiotics results in little to no difference in relation to the severity of HAEC at Grade III (OR 0.43, 95% CI 0.05 to 3.45; I² = 0%; 2 studies, 120 participants; low-certainty evidence). No overall mortality or withdrawals due to adverse events were reported. Probiotics may result in little to no difference in the recurrence of episodes of HAEC compared to placebo (OR 0.85, 95% CI 0.24 to 3.00; 1 study, 60 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is currently not enough evidence to assess the efficacy or safety of probiotics for the prevention of Hirschsprung-associated enterocolitis when compared with placebo. The presence of low- to very-low certainty evidence suggests that further well-designed and sufficiently powered RCTs are needed to clarify the true efficacy of probiotics.

Neonatal outcomes and indirect consequences following maternal SARS-CoV-2 infection in pregnancy: A systematic review (preprint)

Objectives Identify the association between maternal SARS-CoV-2 infection in pregnancy and individual neonatal morbidities and outcomes, particularly longer-term outcomes such as neurodevelopment. Setting Case-control and cohort studies from any location published after 1st January 2020, including pre-print articles. Participants Neonates born to pregnant women diagnosed with a SARS-CoV-2 infection at any stage during pregnancy, including asymptomatic women. Primary and secondary outcome measures Neonatal mortality and morbidity, including preterm birth, Caesarean delivery, small for gestational age, admission to neonatal intensive care unit, level of respiratory support required, diagnosis of culture-positive sepsis, evidence of brain injury, necrotising enterocolitis, visual or hearing impairment, neurodevelopmental outcomes, and feeding method. These outcomes were selected according to a Core Outcome Set developed between health professionals, researchers and parents. Results The search returned 3234 papers, from which 204 were included with a total of 45,646 infants born to mothers with SARS-CoV-2 infection during pregnancy across 36 countries. We found limited evidence of an increased risk of some neonatal morbidities, including respiratory disease. There was minimal evidence from low-income settings (1 study) and for neonatal outcomes following first trimester infection (17 studies). Neonatal mortality was very rare. Preterm birth, neonatal unit admission and small for gestational age status were more common in infants born following maternal SARS-CoV-2 infection in pregnancy in most larger studies. Conclusions There is limited data on neonatal morbidity and mortality following maternal SARS-CoV-2 infection in pregnancy, particularly from low-income countries and following early pregnancy infections. Large, representative studies addressing these outcomes are needed to better understand the consequences for babies born to women with SARS-CoV-2 in pregnancy. Trial registration PROSPERO ID: CRD42021249818 Strengths and limitations Inclusion of studies of both asymptomatic and symptomatic SARS-CoV-2 infections at any point in pregnancy to maximise generalisability of findings Focus on neonatal outcomes, as opposed to purely obstetric outcomes, to accurately quantify neonatal morbidity Study is limited by available data; important data gap in low-income settings

Clinicopathological findings in patients with COVID-19-associated ischaemic enterocolitis.

AIMS: Coronavirus disease 2019 (COVID-19) has been recognised as a predominantly respiratory tract infection, but some patients manifest severe systemic symptoms/coagulation abnormalities. The aim of this study was to evaluate the impact of severe COVID-19 infection on the gastrointestinal tract. METHODS AND RESULTS: We examined clinicopathological findings in 28 resected ischaemic bowels from 22 patients with severe COVID-19. Most patients required intubation preoperatively and presented with acute decompensation shortly before surgery. D-dimer levels were markedly elevated in all measured cases (mean, 5394 ng/ml). Histologically, 25 cases (19 patients) showed evidence of acute ischaemia with necrosis. In this group, the most characteristic finding was the presence of small vessel fibrin thrombi (24 of 25 cases, 96%), which were numerous in 64% of cases. Patients with COVID-19 were significantly more likely than a control cohort of 35 non-COVID-19-associated acute ischaemic bowels to show isolated small intestine involvement (32% versus 6%, P < 0.001), small vessel fibrin thrombi (100% versus 43%, P < 0.001), submucosal vessels with fibrinous degeneration and perivascular neutrophils (90% versus 54%, P < 0.001), fibrin strands within submucosal vessels (58% versus 20%, P = 0.007), and histological evidence of pneumatosis (74% versus 34%, P = 0.010). Three cases in this cohort had histopathological findings normally seen in the setting of chronic ischaemia, notably prominent fibroblastic proliferation affecting the outer layer of the muscularis propria. CONCLUSIONS: Herein, we describe the histopathological findings in COVID-19-associated ischaemic bowels and postulate a relationship with the hypercoagulable state seen in patients with severe COVID-19 infection. Additional experience with these cases may further elucidate specific features or mechanisms of COVID-19-associated ischaemic enterocolitis.

Case Report: Ischemic Enterocolitis Associated with Coronavirus Disease 2019: Two Case Reports and a Review of the Literature.

The COVID-19 pandemic has caused serious health and social concerns worldwide. Although the primary target of SARS-CoV-2 is the respiratory tract, SARS-CoV-2 infection also causes extrapulmonary symptoms. Previous articles have reported ischemic colitis in COVID-19 patients; however, information regarding its clinical manifestations and pathophysiology is limited. In this case report, we present two cases of ischemic enterocolitis in COVID-19 patients and review past case reports. Our literature review has shown that computed tomography rather than endoscopy was used for the diagnosis, and any region of the intestine was affected. Because the elevation of the D-dimer, which suggested a hypercoagulable state, was reported in most cases, we assumed that thrombosis at any level in the artery and vein was involved in the pathophysiology of COVID-19-associated enterocolitis. SARS-CoV-2-induced endotheliitis can cause both coarctation of the vessels and thrombosis; therefore, both patterns of ischemic colitis, occlusive and nonocclusive, may be involved in COVID-19-associated enterocolitis.

Cytomegalovirus haemorrhagic enterocolitis associated with severe infection with COVID-19.

We present a case of haemorrhagic enterocolitis in a patient with SARS-CoV-2 who recovered from respiratory failure after support with venovenous extracorporeal membrane oxygenation. We describe clinicopathological features consistent with the systemic coinfection/reactivation of cytomegalovirus (CMV) concurrent with COVID-19 infection and the protracted clinical course of resolution of gastrointestinal inflammation after the treatment of CMV infection. Stool PCR, abdominal CT perfusion scan and histological examination of ileal and colonic tissues excluded enterocolitis secondary to other causes of infection (common viral, bacterial and protozoal gastrointestinal pathogens), macrovascularand microvascular ischaemia and classic inflammatory bowel disease, respectively. We propose possible synergistic pathophysiologic mechanisms for enterocolitis complicating severe COVID-19 infection: (1) T lymphocyte depletion and immune response dysregulation, (2) use of immunomodulators in the management of severe COVID-19 infection and (3) high concentration of ACE-2 receptors for COVID-19 virus in the gastrointestinal tract.

Aminopeptidase N Expression, Not Interferon Responses, Determines the Intestinal Segmental Tropism of Porcine Deltacoronavirus.

Porcine deltacoronavirus (PDCoV) is an economically important enteropathogen of swine with worldwide distribution. PDCoV primarily infects the small intestine instead of the large intestine in vivo However, the underlying mechanism of PDCoV tropism to different intestinal segments remains poorly understood as a result of the lack of a suitable in vitro intestinal model that recapitulates the cellular diversity and complex functions of the gastrointestinal tract. Here, we established the PDCoV infection model of crypt-derived enteroids from different intestinal segments. Enteroids were susceptible to PDCoV, and multiple types of different functional intestinal epithelia were infected by PDCoV in vitro and in vivo We further found that PDCoV favorably infected the jejunum and ileum and restrictedly replicated in the duodenum and colon. Mechanistically, enteroids from different intestinal regions displayed a distinct gene expression profile, and the differential expression of primary viral receptor host aminopeptidase N (APN) instead of the interferon (IFN) responses determined the susceptibility of different intestinal segments to PDCoV, although PDCoV substantially elicited antiviral genes production in enteroids after infection. Additional studies showed that PDCoV infection significantly induced the expression of type I and III IFNs at the late stage of infection, and exogenous IFN inhibited PDCoV replication in enteroids. Hence, our results provide critical inputs to further dissect the molecular mechanisms of PDCoV-host interactions and pathogenesis.IMPORTANCE The zoonotic potential of the PDCoV, a coronavirus efficiently infecting cells from a broad range species, including porcine, chicken, and human, emphasizes the urgent need to further study the cell and tissue tropism of PDCoV in its natural host. Herein, we generated crypt stem cell-derived enteroids from porcine different intestinal regions, which well recapitulated the events in vivo of PDCoV infection that PDCoV targeted multiple types of intestinal epithelia and preferably infected the jejunum and ileum over the duodenum and colon. Mechanistically, we demonstrated that the expression of APN receptor rather than the IFN responses determined the susceptibility of different regions of the intestines to PDCoV infection, though PDCoV infection markedly elicited the IFN responses. Our findings provide important insights into how the distinct gene expression profiles of the intestinal segments determine the cell and tissue tropism of PDCoV.

Quantitative Proteomic Analysis of the Expression of SARS-CoV-2 Receptors in the Gut of Patients with Chronic Enterocolitis.

The cellular entry of severe respiratory syndrome coronavirus-2 (SARS-CoV-2) is mediated by interaction with the human angiotensin-converting enzyme 2 (ACE2), a receptor that is expressed on both lung and intestinal epithelial cells. We performed a quantitative proteomic analysis to investigate the expression of possible receptors for SARS-CoV-2 in the intestinal mucosa of 23 patients with chronic colitis. ACE2 expression was low and remained unaltered in the gut of patients with ulcerative colitis (UC), Crohn's disease (CD), intestinal Behcet's disease (BD), and intestinal tuberculosis (TB), when compared with that of healthy individuals. Additionally, the expression levels of some probable co-receptors, including dipeptidyl peptidase 4 (DPP4), aminopeptidase N (AMPN), and glutamyl aminopeptidase (AMPE), were unchanged in the affected UC, CD, intestinal BD, and intestinal TB colon mucosa samples. In conclusion, gut inflammation associated with chronic colitis does not mediate a further increase in the cellular entry of SARS-CoV-2.

Time-dependent management of Hirschsprung disease during Covid-19 pandemic (preprint)

INTRODUCTION – During Covid-19 pandemic, some elective non-deferrable surgical procedures has been maintained on a local basis to avoid complications of time-dependent issues. The aim of this paper is to suggest a possible strategy for the management of patients with Hirschsprung (HSCR) during this dramatic Covid-19 pandemic considering.MATERIALS AND METHODS - A systematic literature search on PubMed and Embase of all available literature addressing “Hirschsprung”, “preoperative enterocolitis”, “preoperative mortality”, “complications”, and “timing” in all possible combination has been performed limiting documents to the last 10 years and excluding non-English papers.RESULTS – Systematic review assessed 170 papers and focused on 10 full-text papers addressing the same issues as above. The incidence of preoperative HAEC proved to be as high as 34% with a mortality between 2.4% and 8%. Age at surgery varied in literature reports but recent evidences suggested that patients should be operated around 3 months of age after effective bowel decompression. Rectal irrigations should not be continued over 2 to 4 months to avoid nutritional issues and subsequent possible increase of surgical complications.CONCLUSIONS – Based on available literature, contingent shortage of health resources and necessity to avoid hospital overcrowding during this pandemic, we suggest as follows: 1) surgery should be delayed for healthy neonates up to 3 months of age, and a diverting enterostomy consider for those with ultralong HSCR, unwell or with ineffective nursing; 2) surgery can be delayed but rectal irrigations cannot be maintained indefinitely (ideally within 2 to 4 months at maximum); 3) Surgery could be postponed in older patients, provided previous bouts of HAEC are excluded. This chosen behaviour of our Center for Digestive Diseases aims at avoiding risk of complication and serve the best for our patients in this delicate setting of Covid-19 pandemic.

Computerized tomography scan findings of a patient with severe enterocolitis associated with the coronavirus disease 2019: a case report (preprint)

Background: Currently, there is no available study about the occurrence of enterocolitis associated with the coronavirus disease 2019 (COVID-19) among adults. Case presentation: A 56-year-old man had lower abdominal pain, distension, diarrhea, and bloody stool. Moreover, the patient presented with fever and general fatigue. Laboratory examination did not reveal leukocytosis nor neutrophilia. However, the patient’s C-reactive protein level increased to 4.9 (normal range: 0.0–0.3) mg/dL. Both sputum and stool cultures had normal results. However, abdominal computed tomography (CT) scan revealed wall thickness mainly in the submucosal layer of the left part of the large intestine. Thus, real-time polymerase chain reaction test of throat swabs was performed for the diagnosis of COVID-19, and positive results were obtained. Conclusions: We report the first case of enterocolitis correlated to COVID-19, and the patient had positive abdominal CT scan findings. This imaging modality could be effective for the diagnosis of enterocolitis associated with COVID-19.