Limited extent and consequences of pancreatic SARS-CoV-2 infection

Verena van der Heide, Sonia Jangra, Phillip Cohen, Raveen Rathnasinghe, Sadaf Aslam, Teresa Aydillo, Daniel Geanon, Diana Handler, Geoffrey Kelley, Brian Lee, Adeeb Rahman, Travis Dawson, Jingjing Qi, Darwin D'Souza, Seunghee Kim-Schulze, Julia K. Panzer, Alejandro Caicedo, Irina Kusmartseva, Amanda L. Posgai, Mark A. AtkinsonRandy A. Albrecht, Adolfo García-Sastre, Brad R. Rosenberg, Michael Schotsaert, Dirk Homann

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article number110508
JournalCell Reports
Volume38
Issue number11
DOIs
StatePublished - Mar 15 2022
Externally publishedYes

Keywords

  • COVID-19
  • SARS-CoV-2
  • human coronaviruses
  • human islets
  • pancreas
  • type 1 diabetes
  • type 2 diabetes
  • viral infection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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