tetano
Editor, Senior Moderator
Cell Rep
. 2022 Feb 21;110508.
doi: 10.1016/j.celrep.2022.110508. Online ahead of print.
Limited extent and consequences of pancreatic SARS-CoV-2 infection
Verena van der Heide[SUP] 1 [/SUP], Sonia Jangra[SUP] 2 [/SUP], Phillip Cohen[SUP] 3 [/SUP], Raveen Rathnasinghe[SUP] 2 [/SUP], Sadaf Aslam[SUP] 2 [/SUP], Teresa Aydillo[SUP] 2 [/SUP], Daniel Geanon[SUP] 4 [/SUP], Diana Handler[SUP] 4 [/SUP], Geoffrey Kelley[SUP] 4 [/SUP], Brian Lee[SUP] 4 [/SUP], Adeeb Rahman[SUP] 4 [/SUP], Travis Dawson[SUP] 4 [/SUP], Jingjing Qi[SUP] 4 [/SUP], Darwin D'Souza[SUP] 4 [/SUP], Seunghee Kim-Schulze[SUP] 5 [/SUP], Julia K Panzer[SUP] 6 [/SUP], Alejandro Caicedo[SUP] 6 [/SUP], Irina Kusmartseva[SUP] 7 [/SUP], Amanda L Posgai[SUP] 7 [/SUP], Mark A Atkinson[SUP] 8 [/SUP], Randy A Albrecht[SUP] 2 [/SUP], Adolfo García-Sastre[SUP] 9 [/SUP], Brad R Rosenberg[SUP] 3 [/SUP], Michael Schotsaert[SUP] 10 [/SUP], Dirk Homann[SUP] 11 [/SUP]
Affiliations
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.
Keywords: COVID-19; SARS-CoV-2; human coronaviruses; human islets; pancreas; type 1 diabetes; type 2 diabetes; viral infection.
. 2022 Feb 21;110508.
doi: 10.1016/j.celrep.2022.110508. Online ahead of print.
Limited extent and consequences of pancreatic SARS-CoV-2 infection
Verena van der Heide[SUP] 1 [/SUP], Sonia Jangra[SUP] 2 [/SUP], Phillip Cohen[SUP] 3 [/SUP], Raveen Rathnasinghe[SUP] 2 [/SUP], Sadaf Aslam[SUP] 2 [/SUP], Teresa Aydillo[SUP] 2 [/SUP], Daniel Geanon[SUP] 4 [/SUP], Diana Handler[SUP] 4 [/SUP], Geoffrey Kelley[SUP] 4 [/SUP], Brian Lee[SUP] 4 [/SUP], Adeeb Rahman[SUP] 4 [/SUP], Travis Dawson[SUP] 4 [/SUP], Jingjing Qi[SUP] 4 [/SUP], Darwin D'Souza[SUP] 4 [/SUP], Seunghee Kim-Schulze[SUP] 5 [/SUP], Julia K Panzer[SUP] 6 [/SUP], Alejandro Caicedo[SUP] 6 [/SUP], Irina Kusmartseva[SUP] 7 [/SUP], Amanda L Posgai[SUP] 7 [/SUP], Mark A Atkinson[SUP] 8 [/SUP], Randy A Albrecht[SUP] 2 [/SUP], Adolfo García-Sastre[SUP] 9 [/SUP], Brad R Rosenberg[SUP] 3 [/SUP], Michael Schotsaert[SUP] 10 [/SUP], Dirk Homann[SUP] 11 [/SUP]
Affiliations
- PMID: 35247306
- DOI: 10.1016/j.celrep.2022.110508
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.
Keywords: COVID-19; SARS-CoV-2; human coronaviruses; human islets; pancreas; type 1 diabetes; type 2 diabetes; viral infection.