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SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes.

ABSTRACT: Evidence suggests an association between severe acute respiratory syndrome-cornavirus-2 (SARS-CoV-2) infection and the occurrence of new-onset diabetes. We examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), the cell entry factors for SARS-CoV-2, using publicly available single-cell RNA sequencing data sets, and pancreatic tissue from control male and female nonhuman primates (NHPs) and humans. We also examined SARS-CoV-2 immunolocalization in pancreatic cells of SARS-CoV-2-infected NHPs and patients who had died from coronavirus disease 2019 (COVID-19). We report expression of ACE2 in pancreatic islet, ductal, and endothelial cells in NHPs and humans. In pancreata from SARS-CoV-2-infected NHPs and COVID-19 patients, SARS-CoV-2 infected ductal, endothelial, and islet cells. These pancreata also exhibited generalized fibrosis associated with multiple vascular thrombi. Two out of 8 NHPs developed new-onset diabetes following SARS-CoV-2 infection. Two out of 5 COVID-19 patients exhibited new-onset diabetes at admission. These results suggest that SARS-CoV-2 infection of the pancreas may promote acute and especially chronic pancreatic dysfunction that could potentially lead to new-onset diabetes.

SUBMITTER: Qadir MMF

PROVIDER: S-EPMC8410013 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes.

Qadir Mirza Muhammad Fahd MMF Bhondeley Manika M Beatty Wandy W Gaupp Dina D DD Doyle-Meyers Lara A LA Fischer Tracy T Bandyopadhyay Ishitri I Blair Robert V RV Bohm Rudolf R Rappaport Jay J Lazartigues Eric E Heide Richard S Vander RSV Kolls Jay K JK Qin Xuebin X Mauvais-Jarvis Franck F

JCI insight 20210823 16

Evidence suggests an association between severe acute respiratory syndrome-cornavirus-2 (SARS-CoV-2) infection and the occurrence of new-onset diabetes. We examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), the cell entry factors for SARS-CoV-2, using publicly available single-cell RNA sequencing data sets, and pancreatic tissue from control male and female nonhuman primates (NHPs) and humans. We also examined SARS-CoV-2 immuno ...[more]

PMID: 34241597

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Project description:ImportanceIn adults, diagnoses of new-onset type 2 diabetes (T2D) have increased following diagnosis with COVID-19, but whether this occurs in children is unclear.ObjectiveTo determine whether risk of incident T2D diagnosis is increased during the 6 months after SARS-CoV-2 infection among children.Design, setting, and participantsThis retrospective cohort study used electronic health records from the TriNetX analytics platforms between January 1, 2020, and December 31, 2022. Pediatric patients aged 10 to 19 years without preexisting diabetes were eligible for inclusion. Data were analyzed from August 15 to September 15, 2023, with supplemental analyses January 20 and August 8 to 13, 2024.ExposuresDiagnosis of COVID-19 or a non-COVID-19 respiratory infection.Main outcomes and measuresNew diagnosis of T2D compared by risk ratios (RRs) and 95% CIs at 1, 3, and 6 months after index infection.ResultsThe main study population included 613 602 patients, consisting of 306 801 with COVID-19 (mean [SD] age at index, 14.9 [2.9] years; 52.8% female) and 306 801 with other respiratory infections (ORIs) but no documented COVID-19 (mean [SD] age at index, 14.9 [2.9] years; 52.6% female) after propensity score matching. Risk of a new diagnosis of T2D was significantly increased from day of infection to 1, 3, and 6 months after COVID-19 diagnosis compared with the matched cohort with ORIs (RR at 1 month, 1.55 [95% CI, 1.28-1.89]; RR at 3 months: 1.48 [95% CI, 1.24-1.76]; RR at 6 months: 1.58 [95% CI, 1.35-1.85]). Similar results were found in the subpopulation classified as having overweight or obesity (RR at 1 month: 2.07 [95% CI, 1.12-3.83]; RR at 3 months: 2.00 [95% CI, 1.15-3.47]; RR at 6 months: 2.27 [95% CI, 1.38-3.75]) and the hospitalized subpopulation (RR at 1 month: 3.10 [95% CI, 2.04-4.71]; RR at 3 months: 2.74 [95% CI, 1.90-3.96]; RR at 6 months: 2.62 [95% CI, 1.87-3.66]). Similar elevation in risk was found at 3 and 6 months when excluding patients diagnosed during the interval from the index date to 1 month after infection.Conclusions and relevanceIn this retrospective cohort study of children and adolescents aged 10 to 19 years, the risk of an incident diagnosis of T2D was greater following a COVID-19 diagnosis than in children diagnosed with ORIs. Further study is required to determine whether diabetes persists or reverses later in life.

Project description:BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is a rare chronic neuroinflammatory autoimmune condition. Since the onset of the COVID-19 pandemic, there have been reports of NMOSD clinical manifestations following both SARS-CoV-2 infections and COVID-19 vaccinations.ObjectiveThis study aims to systematically review the published literature of NMOSD clinical manifestations associated with SARS-CoV-2 infections and COVID-19 vaccinations.MethodsA Boolean search of the medical literature was conducted between December 1, 2019 to September 1, 2022, utilizing Medline, Cochrane Library, Embase, Trip Database, Clinicaltrials.gov, Scopus, and Web of Science databases. Articles were collated and managed on Covidence® software. The authors independently appraised the articles for meeting study criteria and followed PRISMA guidelines. The literature search included all case reports and case series that met study criteria and involved NMOSD following either the SARS-CoV-2 infection or the COVID-19 vaccination.ResultsA total of 702 articles were imported for screening. After removing 352 duplicates and 313 articles based on exclusion criteria, 34 articles were analyzed. A total of 41 cases were selected, including 15 patients that developed new onset NMOSD following a SARS-CoV-2 infection, 21 patients that developed de novo NMOSD following COVID-19 vaccination, 3 patients with known NMOSD that experienced a relapse following vaccination, and 2 patients with presumed Multiple Sclerosis (MS) that was unmasked as NMOSD post-vaccination. There was a female preponderance of 76% among all NMOSD cases. The median time interval between the initial SARS-CoV-2 infection symptoms and NMOSD symptom onset was 14 days (range 3-120 days) and the median interval between COVID-19 vaccination and onset of NMO symptoms was 10 days (range 1 to 97 days). Transverse myelitis was the most common neurological manifestation in all patient groups (27/41). Management encompassed acute treatments such as high dose intravenous methylprednisolone, plasmapheresis, and intravenous immunoglobulin (IVIG) and maintenance immunotherapies. The majority of patients experienced a favorable outcome with complete or partial recovery, but 3 patients died.ConclusionThis systematic review suggests that there is an association between NMOSD and SARS-CoV-2 infections and COVID-19 vaccinations. This association requires further study using quantitative epidemiological assessments in a large population to better quantify the risk.

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SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes.

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SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes.

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