-
Cell Reports Mar 2022Concerns that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), may cause...
Concerns that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), may cause new-onset diabetes persist in an evolving research landscape, and precise risk assessment is hampered by, at times, conflicting evidence. Here, leveraging comprehensive single-cell analyses of in vitro SARS-CoV-2-infected human pancreatic islets, we demonstrate that productive infection is strictly dependent on the SARS-CoV-2 entry receptor ACE2 and targets practically all pancreatic cell types. Importantly, the infection remains highly circumscribed and largely non-cytopathic and, despite a high viral burden in infected subsets, promotes only modest cellular perturbations and inflammatory responses. Similar experimental outcomes are also observed after islet infection with endemic coronaviruses. Thus, the limits of pancreatic SARS-CoV-2 infection, even under in vitro conditions of enhanced virus exposure, challenge the proposition that in vivo targeting of β cells by SARS-CoV-2 precipitates new-onset diabetes. Whether restricted pancreatic damage and immunological alterations accrued by COVID-19 increase cumulative diabetes risk, however, remains to be evaluated.
Topics: COVID-19; Diabetes Mellitus; Humans; Insulin-Secreting Cells; Pancreas; SARS-CoV-2
PubMed: 35247306
DOI: 10.1016/j.celrep.2022.110508 -
Journal of Molecular Medicine (Berlin,... Aug 2023Altered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying...
Altered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying the causes of endocrine dysfunctions are lacking. Transcript levels of endocrine-specific genes were analyzed in five endocrine organs of lethal COVID-19 cases. Overall, 116 autoptic specimens from 77 individuals (50 COVID-19 cases and 27 uninfected controls) were included. Samples were tested for the SARS-CoV-2 genome. The adrenals, pancreas, ovary, thyroid, and white adipose tissue (WAT) were investigated. Transcript levels of 42 endocrine-specific and 3 interferon-stimulated genes (ISGs) were measured and compared between COVID-19 cases (virus-positive and virus-negative in each tissue) and uninfected controls. ISG transcript levels were enhanced in SARS-CoV-2-positive tissues. Endocrine-specific genes (e.g., HSD3B2, INS, IAPP, TSHR, FOXE1, LEP, and CRYGD) were deregulated in COVID-19 cases in an organ-specific manner. Transcription of organ-specific genes was suppressed in virus-positive specimens of the ovary, pancreas, and thyroid but enhanced in the adrenals. In WAT of COVID-19 cases, transcription of ISGs and leptin was enhanced independently of virus detection in tissue. Though vaccination and prior infection have a protective role against acute and long-term effects of COVID-19, clinicians must be aware that endocrine manifestations can derive from virus-induced and/or stress-induced transcriptional changes of individual endocrine genes. KEY MESSAGES: • SARS-CoV-2 can infect adipose tissue, adrenals, ovary, pancreas and thyroid. • Infection of endocrine organs induces interferon response. • Interferon response is observed in adipose tissue independently of virus presence. • Endocrine-specific genes are deregulated in an organ-specific manner in COVID-19. • Transcription of crucial genes such as INS, TSHR and LEP is altered in COVID-19.
Topics: Female; Humans; COVID-19; SARS-CoV-2; Interferons; Pancreas
PubMed: 37246981
DOI: 10.1007/s00109-023-02334-3 -
Archivos Argentinos de Pediatria Feb 2023Pancreatic echinococcosis accounts for 0.2-0.6% of cases, with the pediatric population being at a higher risk. Most commonly, pancreatic lesions occur in the head of...
Pancreatic echinococcosis accounts for 0.2-0.6% of cases, with the pediatric population being at a higher risk. Most commonly, pancreatic lesions occur in the head of the pancreas (50-58%); and in the body and tail in 24-34% and 19% of cases, respectively. Given the potential complications, surgery is usually performed. Albendazole is recommended before and after the surgery due to the risks for rupture and dissemination of protoscolices. Here we describe the case of a 5-year-old girl with progressive abdominalpain and cystic lesion in the pancreas compatible with echinococcosis in the ultrasound. The computed tomography showed bile duct compression. Indirect hemagglutination was negative. She had elevated total bilirubin, with a clear predominance of direct bilirubin, and high liver enzymes. Exploratory laparotomy, cholecystectomy, and unroofing of the cyst were performed. The patient had a favorable course and continued with albendazole for 3 months after the surgery.
Topics: Female; Humans; Child; Child, Preschool; Albendazole; Pancreatic Diseases; Echinococcosis; Abdomen; Pancreas
PubMed: 36194666
DOI: 10.5546/aap.2021-02500.eng -
Frontiers in Cellular and Infection... 2021COVID-19 pandemic has infected more than 154 million people worldwide and caused more than 3.2 million deaths. It is transmitted by the Severe Acute Respiratory Syndrome...
COVID-19 pandemic has infected more than 154 million people worldwide and caused more than 3.2 million deaths. It is transmitted by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and affects the respiratory tract as well as extra-pulmonary systems, including the pancreas, that express the virus entry receptor, Angiotensin-Converting Enzyme 2 (ACE2) receptor. Importantly, the endocrine and exocrine pancreas, the latter composed of ductal and acinar cells, express high levels of ACE2, which correlates to impaired functionality characterized as acute pancreatitis observed in some cases presenting with COVID-19. Since acute pancreatitis is already one of the most frequent gastrointestinal causes of hospitalization in the U.S. and the majority of studies investigating the effects of SARS-CoV-2 on the pancreas are clinical and observational, we utilized human iPSC technology to investigate the potential deleterious effects of SARS-CoV-2 infection on iPSC-derived pancreatic cultures containing endocrine and exocrine cells. Interestingly, iPSC-derived pancreatic cultures allow SARS-CoV-2 entry and establish infection, thus perturbing their normal molecular and cellular phenotypes. The infection increased a key cytokine, CXCL12, known to be involved in inflammatory responses in the pancreas. Transcriptome analysis of infected pancreatic cultures confirmed that SARS-CoV-2 hijacks the ribosomal machinery in these cells. Notably, the SARS-CoV-2 infectivity of the pancreas was confirmed in post-mortem tissues from COVID-19 patients, which showed co-localization of SARS-CoV-2 in pancreatic endocrine and exocrine cells and increased the expression of some pancreatic ductal stress response genes. Thus, we demonstrate that SARS-CoV-2 can directly infect human iPSC-derived pancreatic cells with strong supporting evidence of presence of the virus in post-mortem pancreatic tissue of confirmed COVID-19 human cases. This novel model of iPSC-derived pancreatic cultures will open new avenues for the comprehension of the SARS-CoV-2 infection and potentially establish a platform for endocrine and exocrine pancreas-specific antiviral drug screening.
Topics: Acute Disease; COVID-19; Humans; Pancreas; Pancreatitis; Pandemics; SARS-CoV-2
PubMed: 34282405
DOI: 10.3389/fcimb.2021.678482 -
The Cochrane Database of Systematic... May 2010Pancreatic necrosis may complicate severe acute pancreatitis, and is detectable by computed tomography (CT). If it becomes infected mortality increases, but the use of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic necrosis may complicate severe acute pancreatitis, and is detectable by computed tomography (CT). If it becomes infected mortality increases, but the use of prophylactic antibiotics raises concerns about antibiotic resistance and fungal infection.
OBJECTIVES
To determine the efficacy and safety of prophylactic antibiotics in acute pancreatitis complicated by CT proven pancreatic necrosis.
SEARCH STRATEGY
Searches were updated in November 2008, in The Cochrane Library (Issue 2, 2008), MEDLINE, EMBASE, and CINAHL. Conference proceedings and references from found articles were also searched.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing antibiotics versus placebo in acute pancreatitis with CT proven necrosis.
DATA COLLECTION AND ANALYSIS
Primary outcomes were mortality and pancreatic infection rates. Secondary end-points included non pancreatic infection, all sites infection, operative rates, fungal infections, and antibiotic resistance. Subgroup analyses were performed for antibiotic regimen (beta-lactam, quinolone, and imipenem).
MAIN RESULTS
Seven evaluable studies randomised 404 patients. There was no statistically significant effect on reduction of mortality with therapy: 8.4% versus controls 14.4%, and infected pancreatic necrosis rates: 19.7% versus controls 24.4%. Non-pancreatic infection rates and the incidence of overall infections were not significantly reduced with antibiotics: 23.7% versus 36%; 37.5% versus 51.9% respectively. Operative treatment and fungal infections were not significantly different. Insufficient data were provided concerning antibiotic resistance.With beta-lactam antibiotic prophylaxis there was less mortality (9.4% treatment, 15% controls), and less infected pancreatic necrosis (16.8% treatment group, 24.2% controls) but this was not statistically significant. The incidence of non-pancreatic infections was non-significantly different (21% versus 32.5%), as was the incidence of overall infections (34.4% versus 52.8%), and operative treatment rates. No significant differences were seen with quinolone plus imidazole in any of the end points measured. Imipenem on its own showed no difference in the incidence of mortality, but there was a significant reduction in the rate of pancreatic infection (p=0.02; RR 0.34, 95% CI 0.13 to 0.84).
AUTHORS' CONCLUSIONS
No benefit of antibiotics in preventing infection of pancreatic necrosis or mortality was found, except for when imipenem (a beta-lactam) was considered on its own, where a significantly decrease in pancreatic infection was found. None of the studies included in this review were adequately powered. Further better designed studies are needed if the use of antibiotic prophylaxis is to be recommended.
Topics: Acute Disease; Antibiotic Prophylaxis; Bacterial Infections; Humans; Necrosis; Pancreas; Pancreatitis; Pancreatitis, Acute Necrotizing; Randomized Controlled Trials as Topic; Superinfection
PubMed: 20464721
DOI: 10.1002/14651858.CD002941.pub3 -
Gastroenterology May 2020
Topics: Channelopathies; Humans; Liver Cirrhosis; Macrophages; Pancreas; Pancreatitis, Chronic; Peritonitis; Phenotype
PubMed: 32205170
DOI: 10.1053/j.gastro.2020.03.027 -
United European Gastroenterology Journal Sep 2021The COVID-19 pandemic has created unprecedented challenges in all fields of society with social, economic, and health-related consequences worldwide. In this context,... (Review)
Review
BACKGROUND
The COVID-19 pandemic has created unprecedented challenges in all fields of society with social, economic, and health-related consequences worldwide. In this context, gastroenterology patients and healthcare systems and professionals have seen their routines changed and were forced to adapt, adopting measures to minimize the risk of infection while guaranteeing continuous medical care to chronic patients.
OBJECTIVE
At this point, it is important to evaluate the impact of the pandemic on this field to further improve the quality of the services provided in this context.
METHODS/RESULTS/CONCLUSION
We performed a literature review that summarizes the main aspects to consider in gastroenterology, during the pandemic crisis, and includes a deep discussion on the main changes affecting gastroenterology patients and healthcare systems, anticipating the pandemic recovery scenario with future practices and policies.
Topics: Biomarkers; COVID-19; Delivery of Health Care; Disease Management; Endoscopy, Digestive System; Gastroenterology; Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Liver Diseases; Liver Transplantation; Pancreas; Risk Factors; SARS-CoV-2; Telemedicine
PubMed: 34190413
DOI: 10.1002/ueg2.12115 -
Cold Spring Harbor Perspectives in... Jan 2012The precise etiology of type 1 diabetes (T1D) is still unknown, but viruses have long been suggested as a potential environmental trigger for the disease. However,... (Review)
Review
The precise etiology of type 1 diabetes (T1D) is still unknown, but viruses have long been suggested as a potential environmental trigger for the disease. However, despite decades of research, the body of evidence supporting a relationship between viral infections and initiation or acceleration of islet autoimmunity remains largely circumstantial. The most robust association with viruses and T1D involves enterovirus species, of which some strains have the ability to induce or accelerate disease in animal models. Several hypotheses have been formulated to mechanistically explain how viruses may affect islet autoimmunity and β-cell decay. The recent observation that certain viral infections, when encountered at the right time and infectious dose, can prevent autoimmune diabetes illustrates that potential relationships may be more complex than previously thought. Here, we provide a concise summary of data obtained in mouse models and humans, and identify future avenues toward a better characterization of the association between viruses and T1D.
Topics: Animals; Bystander Effect; Diabetes Mellitus, Type 1; Disease Models, Animal; Humans; Immunization; Islets of Langerhans; Mice; Molecular Mimicry; Pancreas; Viral Vaccines; Virus Diseases
PubMed: 22315719
DOI: 10.1101/cshperspect.a007682 -
Frontiers in Cellular and Infection... 2023
Topics: Humans; Pancreatitis; Acute Disease; Pancreas; Infections
PubMed: 37026058
DOI: 10.3389/fcimb.2023.1175195 -
Acta Physiologica (Oxford, England) Dec 2021The molecular link between SARS-CoV-2 infection and susceptibility is not well understood. Nonetheless, a bi-directional relationship between SARS-CoV-2 and diabetes has... (Review)
Review
The molecular link between SARS-CoV-2 infection and susceptibility is not well understood. Nonetheless, a bi-directional relationship between SARS-CoV-2 and diabetes has been proposed. The angiotensin-converting enzyme 2 (ACE2) is considered as the primary protein facilitating SARS-CoV and SARS-CoV-2 attachment and entry into the host cells. Studies suggested that ACE2 is expressed in the endocrine cells of the pancreas including beta cells, in addition to the lungs and other organs; however, its expression in the islets, particularly beta cells, has been met with some contradiction. Importantly, ACE2 plays a crucial role in glucose homoeostasis and insulin secretion by regulating beta cell physiology. Given the ability of SARS-CoV-2 to infect human pluripotent stem cell-derived pancreatic cells in vitro and the presence of SARS-CoV-2 in pancreatic samples from COVID-19 patients strongly hints that SARS-CoV-2 can invade the pancreas and directly cause pancreatic injury and diabetes. However, more studies are required to dissect the underpinning molecular mechanisms triggered in SARS-CoV-2-infected islets that lead to aggravation of diabetes. Regardless, it is important to understand the function of ACE2 in the pancreatic islets to design relevant therapeutic interventions in combatting the effects of SARS-CoV-2 on diabetes pathophysiology. Herein, we detail the function of ACE2 in pancreatic beta cells crucial for regulating insulin sensitivity, secretion, and glucose metabolism. Also, we discuss the potential role played by ACE2 in aiding SARS-COV-2 entry into the pancreas and the possibility of ACE2 cooperation with alternative entry factors as well as how that may be linked to diabetes pathogenesis.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Diabetes Mellitus; Humans; Insulin-Secreting Cells; SARS-CoV-2
PubMed: 34561952
DOI: 10.1111/apha.13733