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Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
Limited extent and consequences of pancreatic SARS-CoV-2 infection
Verena van der Heide1, Sonia Jangra2, Phillip Cohen3
1Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract:
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.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of human pancreatic islets is limited and non-cytopathic, challenging its direct role in causing new-onset diabetes. Further research is needed to assess long-term diabetes risk from COVID-19 related pancreatic changes.
Area of Science:
- Endocrinology and Metabolism
- Virology
- Immunology
Background:
- Ongoing concerns link severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to new-onset diabetes.
- Conflicting evidence necessitates precise risk assessment regarding COVID-19 and diabetes.
- The SARS-CoV-2 entry receptor, ACE2, is present in human pancreatic islets.
Purpose of the Study:
- To investigate the susceptibility and response of human pancreatic islets to SARS-CoV-2 infection in vitro.
- To determine if SARS-CoV-2 infection of pancreatic islets can precipitate new-onset diabetes.
Main Methods:
- Comprehensive single-cell analyses of in vitro SARS-CoV-2-infected human pancreatic islets.
- Assessment of viral tropism, cytopathic effects, and cellular/inflammatory responses.
- Comparison with endemic coronavirus infections in pancreatic islets.
Main Results:
- Productive SARS-CoV-2 infection is ACE2-dependent and targets all pancreatic cell types within islets.
- Infection is circumscribed, largely non-cytopathic, with modest cellular perturbations and inflammatory responses despite high viral burden.
- Similar outcomes were observed following infection with endemic coronaviruses.
Conclusions:
- The limited in vitro infectivity and non-cytopathic nature of SARS-CoV-2 in human pancreatic islets challenge the hypothesis that direct beta-cell targeting causes new-onset diabetes.
- The potential for cumulative diabetes risk from restricted pancreatic damage and immunological alterations post-COVID-19 requires further evaluation.
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