SARS-CoV-2 infects cells of the human exocrine and endocrine pancreas and interferes with beta-cell function (preprint)

Preexisting diabetes increases the risk of a severe course of the pandemic coronavirus disease 2019 (COVID-19). Vice versa, exacerbations of a preexisting diabetes as well as new-onset diabetes have been reported upon SARS-CoV-2 infection. Thus, there is an imperative need to clarify whether human pancreatic endocrine cells organized within an islet of Langerhans are permissive for and affected by SARS-CoV-2 infection, and to elucidate the mechanisms underlying the development of diabetes upon COVID-19. Here, we (i) defined ACE2 and TMPRSS2 expression patterns in human pancreatic endocrine and exocrine cell types, (ii) employed human pancreatic islet cultures to demonstrate susceptibility to SARS-CoV-2 infection and to viral replication in β-cells, (iii) showed that SARS-CoV-2 attenuates glucose-stimulated insulin secretion, and (iv) tested remdesivir as eventually effective to prevent β-cell failure. In addition, we (v) visualized viral particles replicating in endocrine pancreatic cells and define their subcellular localization patterns via transmission electron microscopy, and finally (vi) present examples of cell type specific pancreatic infection patterns of COVID-19 deceased patients. Overall, our data demonstrate that SARS-CoV-2 can infect both the exocrine and endocrine compartments of the pancreas and can perturb β-cell integrity, which might lead to an increased risk for diabetes.

Remdesivir but not famotidine inhibits SARS-CoV-2 replication in human pluripotent stem cell-derived intestinal organoids (preprint)

Gastrointestinal symptoms in COVID-19 are associated with prolonged symptoms and increased severity. We employed human intestinal organoids derived from pluripotent stem cells (PSC-HIOs) to analyze SARS-CoV-2 pathogenesis and to validate efficacy of specific drugs in the gut. Certain, but not all cell types in PSC-HIOs express SARS-CoV-2 entry factors ACE2 and TMPRSS2, rendering them susceptible to SARS-CoV-2 infection. Remdesivir, a promising drug to treat COVID-19, effectively suppressed SARS-CoV-2 infection of PSC-HIOs. In contrast, the histamine-2-blocker famotidine showed no effect. Thus, PSC-HIOs provide an interesting platform to study SARS-CoV-2 infection and to identify or validate drugs.

A secure and rapid query-software for COVID-19 test results that can easily be integrated into the clinical workflow to avoid communication overload (preprint)

Overcoming the COVID-19 crisis requires new ideas and strategies. Rapid testing of a large number of subjects is essential to monitor, and delay, the spread of SARS-CoV-2 to mitigate the consequences of the pandemic. People not knowing that they are infected may not stay in quarantine and, thus, are a risk for infecting others. Unfortunately, the massive number of COVID-19 tests performed is challenging for both laboratories and the units that take the throat swab and have to communicate test results. Here, we present a secure tracking system (CTest) to report COVID-19 test results online as soon as they become available. The system can be integrated into the clinical workflow with very modest effort and avoids excessive load to telephone hotlines. With this open-source and browser-based online tracking system, we aim to minimize the time required to inform the tested person but also the test units, e.g. hospitals or the public healthcare system. Instead of personal calls, CTest updates the status of the test automatically when the test results are available. Test reports are published on a secured web-page enabling regular status checks also by patients not using smartphones with dedicated mobile apps which has some importance as smartphone usage diminishes with age. The source code, as well as further information to integrate CTest into the IT environment of other clinics or test-centres, are freely available from https://github.com/sysbio-bioinf/CTest under the Eclipse Public License v2.0 (EPL2).