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1.
J Korean Med Sci ; 36(48): e336, 2021 Dec 13.
Article in English | MEDLINE | ID: covidwho-1572279

ABSTRACT

In 2020, the novel coronavirus disease 2019 (COVID-19) began to spread worldwide and remains an ongoing medical challenge. This case series reports on the clinical features and characteristics of patients with inflammatory bowel disease (IBD) and confirmed COVID-19 infection. From February 2020 to March 2021, nine patients with IBD had confirmed COVID-19 across four hospitals in Korea. The median age at COVID-19 diagnosis was 42 years. Six patients were male, and seven patients had ulcerative colitis (UC). No patients required oxygen therapy, intensive care unit hospitalizations, or died. The most common symptom was fever, and gastrointestinal (GI) symptoms developed as diarrhea in five patients with UC. Oral steroids were used to combat UC aggravation in two patients. In this case series of nine IBD patients diagnosed with COVID-19 in Korea, the clinical presentation was predominately a mild respiratory tract infection. Most patients with UC developed new GI symptoms including diarrhea.


Subject(s)
COVID-19/diagnosis , Inflammatory Bowel Diseases/pathology , Administration, Oral , Adult , COVID-19/complications , COVID-19/pathology , COVID-19/virology , Colitis, Ulcerative/complications , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Diarrhea/etiology , Female , Fever/etiology , Hospitalization , Humans , Inflammatory Bowel Diseases/complications , Intensive Care Units , Male , Middle Aged , Republic of Korea , SARS-CoV-2/isolation & purification , Steroids/therapeutic use , Young Adult
2.
J Autoimmun ; 125: 102739, 2021 12.
Article in English | MEDLINE | ID: covidwho-1487809

ABSTRACT

OBJECTIVE: To study long term consequences of hospitalization for COVID-19 in patients with chronic inflammatory diseases. We studied the risk of subsequent hospitalizations in patients with chronic inflammatory diseases, who survived a hospitalization for COVID-19, compared to other patients who had been hospitalized for COVID-19. DESIGN AND SETTING: Population based cohort study based on Danish nationwide health registers. The study population included all adult patients in Denmark who had been discharged alive after a hospitalization with COVID-19 from March 1, 2020 to July 31, 2021. POPULATION: From the study population, the exposed cohort constituted patients who had inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathy (SpA), or psoriatic arthritis (PsA) prior to hospitalization for COVID-19, and the unexposed cohort constituted those without these diseases. MAIN OUTCOME MEASURES: We estimated the adjusted Hazard Rate (aHR) for the following outcomes: overall risk of hospitalization, cardiovascular diseases, respiratory diseases, blood and blood-forming organs, nervous system diseases, infections, sequelae of COVID-19, and death. RESULTS: A total of 417 patients with IBD/RA/SpA/PsA were discharged alive after COVID-19, and 9,248 patients without these diseases. Across the different outcomes examined, the median length of follow up was 6.50 months in the exposed cohort (25-75% percentiles: 4.38-8.12), and among the unexposed the median time of follow up was 6.59 months (25-75% percentiles: 4.17-8.49). Across different analyses, we consistently found a significantly increased risk of hospitalizations due to respiratory diseases (aHR 1.27 (95% CI 1.02-1.58)) and infections (aHR 1.55 (95% CI 1.26-1.92)). In sensitivity analyses, the overall risk of hospitalization was aHR 1.15 (95% CI 0.96-1.38) and the risk of hospitalization due to cardiovascular diagnoses was aHR 1.14 (95% CI 0.91-1.42). During the time of follow up, the risk of nervous system diagnoses or death was not increased in patients with IBD/RA/SpA/PsA. CONCLUSIONS: After hospitalization with COVID-19, patients with IBD/RA/SpA/PsA had an increased risk of subsequent hospitalizations for a number of categories of diseases, compared to other patients who have been hospitalized with COVID-19. These results are disturbing and need to be examined further. The implication of our results is that clinicians should be particularly alert for post COVID-19 symptoms from several organ systems in patients with IBD/RA/SpA/PsA.


Subject(s)
Arthritis, Psoriatic/pathology , Arthritis, Rheumatoid/pathology , COVID-19/therapy , Hospitalization/statistics & numerical data , Inflammatory Bowel Diseases/pathology , Spondylarthritis/pathology , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Denmark/epidemiology , Female , Humans , Male , Middle Aged , Nervous System Diseases/epidemiology , Risk , SARS-CoV-2 , Young Adult
4.
Int J Mol Sci ; 21(11)2020 May 29.
Article in English | MEDLINE | ID: covidwho-1456326

ABSTRACT

In the development of inflammatory bowel disease (IBD), the gut microbiota has been established as a key factor. Recently, metabolomics has become important for understanding the functional relevance of gut microbial changes in disease. Animal models for IBD enable the study of factors involved in disease development. However, results from animal studies may not represent the human situation. The aim of this study was to investigate whether results from metabolomics studies on animal models for IBD were similar to those from studies on IBD patients. Medline and Embase were searched for relevant studies up to May 2017. The Covidence systematic review software was used for study screening, and quality assessment was conducted for all included studies. Data showed a convergence of ~17% for metabolites differentiated between IBD and controls in human and animal studies with amino acids being the most differentiated metabolite subclass. The acute dextran sodium sulfate model appeared as a good model for analysis of systemic metabolites in IBD, but analytical platform, age, and biological sample type did not show clear correlations with any significant metabolites. In conclusion, this systematic review highlights the variation in metabolomics results, and emphasizes the importance of expanding the applied detection methods to ensure greater coverage and convergence between the various different patient phenotypes and animal models of inflammatory bowel disease.


Subject(s)
Inflammatory Bowel Diseases/metabolism , Metabolome , Metabolomics/methods , /methods , Animals , Disease Models, Animal , Humans , Inflammatory Bowel Diseases/etiology , Inflammatory Bowel Diseases/pathology , Mice , Sodium Dodecyl Sulfate/toxicity
5.
Sci Rep ; 11(1): 13533, 2021 06 29.
Article in English | MEDLINE | ID: covidwho-1387483

ABSTRACT

The host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn's disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course. We examined the expression of colonic ACE2 in 67 adult CD and 14 NIBD control patients using RNA-seq and quantitative (q) RT-PCR. We validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increased ACE2 expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients. Colonic ACE2 expression was significantly higher in a subset of adult CD patients which was defined as the ACE2-high CD subset. IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of CD diagnosis, and a Cox regression analysis found that high ACE2 levels is an independent risk factor for surgery (OR 2.17; 95% CI, 1.10-4.26; p = 0.025). Increased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that can impact CD disease-related outcomes.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Crohn Disease/pathology , Adolescent , Adult , Angiotensin-Converting Enzyme 2/genetics , Crohn Disease/metabolism , Crohn Disease/surgery , Female , Humans , Ileum/metabolism , Ileum/pathology , Immunohistochemistry , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Male , Prognosis , Proportional Hazards Models , RNA, Messenger/chemistry , RNA, Messenger/metabolism , Risk Factors , Sequence Analysis, RNA , Young Adult
6.
Cells ; 10(9)2021 08 29.
Article in English | MEDLINE | ID: covidwho-1374308

ABSTRACT

Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of infectious and inflammatory diseases. By releasing these small molecular weight peptides, the source cells can influence numerous intracellular processes in the target cells, including the secretion of other cytokines downstream. However, there are no readily available bioinformatic resources that can model cytokine-cytokine interactions. In this effort, we built a communication map between major tissues and blood cells that reveals how cytokine-mediated intercellular networks form during homeostatic conditions. We collated the most prevalent cytokines from the literature and assigned the proteins and their corresponding receptors to source tissue and blood cell types based on enriched consensus RNA-Seq data from the Human Protein Atlas database. To assign more confidence to the interactions, we integrated the literature information on cell-cytokine interactions from two systems of immunology databases, immuneXpresso and ImmunoGlobe. From the collated information, we defined two metanetworks: a cell-cell communication network connected by cytokines; and a cytokine-cytokine interaction network depicting the potential ways in which cytokines can affect the activity of each other. Using expression data from disease states, we then applied this resource to reveal perturbations in cytokine-mediated intercellular signalling in inflammatory and infectious diseases (ulcerative colitis and COVID-19, respectively). For ulcerative colitis, with CytokineLink, we demonstrated a significant rewiring of cytokine-mediated intercellular communication between non-inflamed and inflamed colonic tissues. For COVID-19, we were able to identify cell types and cytokine interactions following SARS-CoV-2 infection, highlighting important cytokine interactions that might contribute to severe illness in a subgroup of patients. Such findings have the potential to inform the development of novel, cytokine-targeted therapeutic strategies. CytokineLink is freely available for the scientific community through the NDEx platform and the project github repository.


Subject(s)
COVID-19/immunology , Cytokines/metabolism , Immunity , Inflammatory Bowel Diseases/immunology , Cell Communication , Colitis, Ulcerative/immunology , Colitis, Ulcerative/pathology , Databases, Genetic , Humans , Inflammatory Bowel Diseases/pathology , Signal Transduction
7.
Cell Mol Gastroenterol Hepatol ; 12(1): 321-333, 2021.
Article in English | MEDLINE | ID: covidwho-1118539

ABSTRACT

The Inflammatory Bowel Diseases (IBD), Ulcerative Colitis (UC) and Crohn's Disease (CD) are characterised by chronic non-resolving gut mucosal inflammation involving innate and adaptive immune responses. Neutrophils, usually regarded as first responders in inflammation, are a key presence in the gut mucosal inflammatory milieu in IBD. Here, we review the role of neutrophil extracellular trap (NET) formation as a potential effector disease mechanism. NETs are extracellular webs of chromatin, microbicidal proteins and oxidative enzymes that are released by neutrophils to contain pathogens. NETs contribute to the pathogenesis of several immune-mediated diseases such as systemic lupus erythematosus and rheumatoid arthritis; and recently, as a major tissue damaging process involved in the host response to severe acute respiratory syndrome coronavirus 2 infection. NETs are pertinent as a defence mechanism at the gut mucosal interphase exposed to high levels of bacteria, viruses and fungi. On the other hand, NETs can also potentiate and perpetuate gut inflammation. In this review, we discuss the broad protective vs. pathogenic roles of NETs, explanatory factors that could lead to an increase in NET formation in IBD and how NETs may contribute to gut inflammation and IBD-related complications. Finally, we summarise therapeutic opportunities to target NETs in IBD.


Subject(s)
Extracellular Traps/immunology , Inflammatory Bowel Diseases/immunology , Neutrophils/immunology , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , Arthritis, Rheumatoid/therapy , COVID-19/immunology , COVID-19/pathology , COVID-19/therapy , Humans , Inflammatory Bowel Diseases/pathology , Inflammatory Bowel Diseases/therapy , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/pathology , Lupus Erythematosus, Systemic/therapy , Neutrophils/pathology , SARS-CoV-2
8.
Indian J Med Microbiol ; 38(3 & 4): 261-264, 2020.
Article in English | MEDLINE | ID: covidwho-914619

ABSTRACT

Although children with novel coronavirus infection (COVID-19) typically present with fever and respiratory symptoms, some children have reported gastrointestinal (GI) symptoms including vomiting and diarrhoea during the course of the disease. The continuous positive detection of the viral RNA from faeces in children even after nasopharyngeal swabs turned negative suggests that the GI tract may shed virus and a tentative faecal-oral transmission. The presence of angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2, which are the key proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry process, in the GI tract can explain the digestive symptoms in COVID-19. COVID-19 has implications for the management of children with chronic luminal diseases. There is increasing concern regarding the risk that children with inflammatory bowel disease being infected with SARS-CoV-2.


Subject(s)
Coronavirus Infections/pathology , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/pathology , Gastrointestinal Tract/pathology , Pneumonia, Viral/pathology , Betacoronavirus , COVID-19 , Child , Coronavirus Infections/diagnosis , Feces/virology , Gastrointestinal Microbiome/physiology , Gastrointestinal Tract/microbiology , Humans , Inflammatory Bowel Diseases/pathology , Pandemics , Pneumonia, Viral/diagnosis , RNA, Viral/isolation & purification , SARS-CoV-2
9.
Biochem Biophys Res Commun ; 533(4): 1276-1282, 2020 12 17.
Article in English | MEDLINE | ID: covidwho-885206

ABSTRACT

BACKGROUND: The whole world was hit hard by the coronavirus disease-19 (COVID-19). Given that angiotensin I converting enzyme 2 (ACE2) is the viral entry molecule, understanding ACE2 has become a major focus of current COVID-19 research. ACE2 is highly expressed in the gut, but its role has not been fully understood and thus COVID-19 treatments intending to downregulate ACE2 level may cause untoward side effects. Gaining insight into the functions of ACE2 in gut homeostasis therefore merits closer examination, and is beneficial to find potential therapeutic alternatives for COVID-19. METHODS: We took advantage of Ace2 knockout out mice and isolated intestinal organoids to examine the role of ACE2 in intestinal stemness. Inflammatory bowel disease (IBD) mouse model was established by 4% dextran sodium sulfate. LGR5 and KI67 levels were quantitated to reflect the virtue of intestinal stem cells (ISCs). FITC-dextran 4 (FD-4) assay was used to assess intestinal barrier function. RESULTS: Western blotting identified the expression of ACE2 in colon, which was consistent with the results of immunofluorescence and RT-PCR. Moreover, Ace2-/- organoids showed decreased LRG5 and KI67 levels, and elevated calcium concentration. Furthermore, the permeability of ace2-/- organoids was markedly increased compared with ace2+/+ organoids. Collectively, ace2-/- mice were more susceptible than ace2+/+ mice to IBD, including earlier bloody stool, undermined intestinal architecture and more pronounced weight loss. CONCLUSIONS: Our data reveal that ACE2 contributes to the proliferation of intestinal stem cells and hence orchestrates the mucosal homeostasis.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Epithelium/metabolism , Angiotensin-Converting Enzyme 2/deficiency , Animals , Calcium/metabolism , Cell Membrane Permeability , Inflammatory Bowel Diseases/enzymology , Inflammatory Bowel Diseases/pathology , Intestines/pathology , Mice, Inbred C57BL , Mice, Knockout , Organoids/metabolism , Stem Cells/cytology , Stem Cells/metabolism
10.
J Immunol Res ; 2020: 2847316, 2020.
Article in English | MEDLINE | ID: covidwho-852756

ABSTRACT

OBJECTIVES: The COVID-19 epidemic triggered by coronavirus SARS-CoV-2 is rapidly spreading around the globe. This study is aimed at finding out the suspected or confirmed SARS-CoV-2 infection in patients with inflammatory bowel disease (IBD) in Hubei province, China. We also investigated symptoms, medications, life quality, and psychological issues of IBD patients under the ongoing pandemic. METHODS: We conducted a self-reported questionnaire survey via an online survey platform. SARS-CoV-2 infection-related data was collected from IBD patients. The status quo of medications and symptoms of the subjects were investigated. Life quality, depression, and anxiety were measured by clinical questionnaires and rated on scoring systems. RESULTS: A total of 204 IBD patients from Hubei province were included in this study. No suspected or confirmed SARS-CoV-2 infection case was found in this study. As a result of city shutdown, two-thirds of the patients (138/204) in our series reported difficulty in accessing medicines and nearly half of them (73/138) had to discontinue medications. Apart from gastrointestinal symptoms, systemic symptoms were common while respiratory symptoms were rare in the cohort. Though their quality of life was not significantly lowered, depression and anxiety were problems that seriously affected them during the COVID-19 epidemic. CONCLUSIONS: Inaccessibility to medications is a serious problem for IBD patients after city shutdown. Efforts have to be made to address the problems of drug withdrawal and psychological issues that IBD patients suffer from during the COVID-19 outbreak.


Subject(s)
Coronavirus Infections/epidemiology , Health Services Accessibility , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Pneumonia, Viral/epidemiology , Adult , Anxiety/psychology , Betacoronavirus/drug effects , COVID-19 , China/epidemiology , Cross-Sectional Studies , Depression/psychology , Female , Humans , Inflammatory Bowel Diseases/pathology , Male , Pandemics , Quality of Life/psychology , SARS-CoV-2 , Surveys and Questionnaires
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