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

Qadir, Mirza Muhammad Fahd; Bhondeley, Manika; Beatty, Wandy L.; Gaupp, Dina; Doyle-Meyers, Lara A.; Fischer, Tracy; Bandyopadhyay, Ishitri; Blair, Robert V; Bohm, Rudolf P.; Rappaport, Jay; Lazartigues, Eric; Heide, Richard S. Vander; Kolls, Jay K.; Qin, Xuebin; Mauvais-Jarvis, Franck

doi:10.1172/jci.insight.151551

Cited by 46 publications

(65 citation statements)

References 35 publications

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“…Our TEM study results are confirmed by the results of previously published works, revealing the presence of coronavirus virions mainly in vascular endothelial cells of the lungs [63], intestines [64,65], kidneys [66], heart [67], skin [68], brain [69], liver [70], pancreas [71]. Furthermore, the TEM data confirms the hypothesis about the critical role of endothelial dysfunction in the development of multiorgan failure and the fatal outcome of COVID-19 [72,73].…”

Section: Discussionsupporting

confidence: 90%

COVID-19: Multiorgan Dissemination of SARS-CoV-2 Is Driven by Pulmonary Factors

Odilov

Волков

Абдуллаев

et al. 2021

Viruses

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Multi-organ failure is one of the common causes of fatal outcome in COVID-19 patients. However, the pathogenetic association of the SARS-CoV-2 viral load (VL) level with fatal dysfunctions of the lungs, liver, kidneys, heart, spleen and brain, as well as with the risk of death in COVID-19 patients remains poorly understood. SARS-CoV-2 VL in the lungs, heart, liver, kidneys, brain, spleen and lymph nodes have been measured by RT qPCR using the following formula: NSARS-CoV−2/NABL1 × 100. Dissemination of SARS-CoV-2 in 30.5% of cases was mono-organ, and in 63.9% of cases, it was multi-organ. The average SARS-CoV-2 VL in the exudative phase of diffuse alveolar damage (DAD) was 60 times higher than in the proliferative phase. The SARS-CoV-2 VL in the lungs ranged from 0 to 250,281 copies. The “pulmonary factors” of SARS-CoV-2 multi-organ dissemination are the high level of SARS-CoV-2 VL (≥4909) and the exudative phase of DAD. The frequency of SARS-CoV-2 dissemination to lymph nodes was 86.9%, heart–56.5%, spleen–52.2%, liver–47.8%, kidney–26%, and brain–13%. We found no link between the SARS-CoV-2 VL level in the liver, kidneys, and heart and the serum level of CPK, LDH, ALP, ALT, AST and Cr of COVID-19 patients. Isolated detection of SARS-CoV-2 RNA in the myocardium of COVID-19 patients who died from heart failure is possible. The pathogenesis of COVID-19-associated multi-organ failure requires further research in a larger cohort of patients.

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Section: Discussionsupporting

confidence: 90%

COVID-19: Multiorgan Dissemination of SARS-CoV-2 Is Driven by Pulmonary Factors

Odilov

Волков

Абдуллаев

et al. 2021

Viruses

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“…Pancreas : In post-mortem material of COVID-19 patients, the viral N protein was detected in β-cells located in islets of the pancreas, which have been proposed as potential site of viral replication ( Müller et al, 2021 ; Qadir et al, 2021 ). This resulted in an impaired production of insulin upon stimulation with glucose in vitro and could be the reason for the hyperglycemia observed in COVID-19 patients ( Zhu L. et al, 2020 ; Affinati et al, 2021 ; Montefusco et al, 2021 ; Müller et al, 2021 ).…”

Section: Sars-cov-2mentioning

confidence: 99%

COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences

Martínez-Salazar

Holwerda

Stüdle

et al. 2022

Front. Cell Dev. Biol.

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first identified in December 2019 as a novel respiratory pathogen and is the causative agent of Corona Virus disease 2019 (COVID-19). Early on during this pandemic, it became apparent that SARS-CoV-2 was not only restricted to infecting the respiratory tract, but the virus was also found in other tissues, including the vasculature. Individuals with underlying pre-existing co-morbidities like diabetes and hypertension have been more prone to develop severe illness and fatal outcomes during COVID-19. In addition, critical clinical observations made in COVID-19 patients include hypercoagulation, cardiomyopathy, heart arrythmia, and endothelial dysfunction, which are indicative for an involvement of the vasculature in COVID-19 pathology. Hence, this review summarizes the impact of SARS-CoV-2 infection on the vasculature and details how the virus promotes (chronic) vascular inflammation. We provide a general overview of SARS-CoV-2, its entry determinant Angiotensin-Converting Enzyme II (ACE2) and the detection of the SARS-CoV-2 in extrapulmonary tissue. Further, we describe the relation between COVID-19 and cardiovascular diseases (CVD) and their impact on the heart and vasculature. Clinical findings on endothelial changes during COVID-19 are reviewed in detail and recent evidence from in vitro studies on the susceptibility of endothelial cells to SARS-CoV-2 infection is discussed. We conclude with current notions on the contribution of cardiovascular events to long term consequences of COVID-19, also known as “Long-COVID-syndrome”. Altogether, our review provides a detailed overview of the current perspectives of COVID-19 and its influence on the vasculature.

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“…Immunohistochemistry and immunoblot staining patterns in human pancreas samples can vary depending on ACE2 antibody specificity [ 80 , 83 ]. Other explanations for the discrepancy of ACE2 expression levels in β cells have also been discussed, such as low sample size, results based on non-COVID-19 pancreatic tissues [ 75 , 81 , 82 , 83 , 84 ], low detection sensitivity of employed methods [ 85 , 89 ], differences in gender and ethnic background [ 81 , 85 , 86 ], inconsistent methodology for sample preservation or preparation between studies [ 75 ], negative effects of rapid pancreas autolysis for receptor detection [ 82 ], and rapid data evaluation and fast publication turnover [ 75 ]. While the expression of ACE2 on β cells is currently controversial and further research is needed, ACE2 expression in pancreatic ducts and in the microvasculature appears to be acknowledged by some study groups [ 75 ].…”

Section: Sars-cov-2 Receptors and Proteases In β Cellsmentioning

confidence: 99%

“…Reports describing the type of cells and tissues that are positive for SARS-CoV-2 protein or mRNA in the pancreas of infected individuals have been inconsistent. For instance, some reports indicate that SARS-CoV-2 protein/mRNA is specifically found in insulin-positive cells [ 48 ], ductal epithelium but not endocrine tissue [ 83 ]; however, other reports indicate that both endocrine and exocrine tissue are positive for them [ 81 , 84 , 85 , 86 ]. The discrepancies among these reports may be partly due to differences in expression levels of virus receptors between individuals, as well as due to differences in the employed methods for pancreatic hormone and viral-antigen co-staining.…”

Section: The Distribution Of Sars-cov-2 In the Pancreasmentioning

confidence: 99%

SARS-CoV-2 Infection and Pancreatic β Cell Failure

Mine

Nagafuchi

Mori

et al. 2021

Biology

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SARS-CoV-2 infection primarily causes pulmonary symptoms; however, accumulating reports indicate that some patients with COVID-19 have multiple organ dysfunction or failure. Although diabetes is considered a risk factor for severe COVID-19, SARS-CoV-2 infection may also be a causal factor for diabetes mellitus in patients with COVID-19. According to the research reviewed in this paper, the pancreas and pancreatic β cells appear to be targets of SARS-CoV-2 and are damaged by direct or indirect effects of the infection. However, controversial results have been reported between study groups, mainly due to the limited number of cases with diabetes precipitated by COVID-19. In this review, we comprehensively discuss the published findings on the potential association between SARS-CoV-2 infection or COVID-19 and pancreatic β-cell damage leading to diabetes onset. These findings will further contribute to our understanding of the pathogenesis of diabetes mellitus.

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

Abstract: SARS-CoV-2 infection of the pancreas promotes thrombo-fibrosis and is associated with new-onset diabetes

Cited by 46 publications

References 35 publications

COVID-19: Multiorgan Dissemination of SARS-CoV-2 Is Driven by Pulmonary Factors

COVID-19: Multiorgan Dissemination of SARS-CoV-2 Is Driven by Pulmonary Factors

COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences

SARS-CoV-2 Infection and Pancreatic β Cell Failure

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