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.

Cell Reports
|March 5, 2022
PubMed

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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