TY - JOUR
T1 - Limited extent and consequences of pancreatic SARS-CoV-2 infection
AU - van der Heide, Verena
AU - Jangra, Sonia
AU - Cohen, Phillip
AU - Rathnasinghe, Raveen
AU - Aslam, Sadaf
AU - Aydillo, Teresa
AU - Geanon, Daniel
AU - Handler, Diana
AU - Kelley, Geoffrey
AU - Lee, Brian
AU - Rahman, Adeeb
AU - Dawson, Travis
AU - Qi, Jingjing
AU - D'Souza, Darwin
AU - Kim-Schulze, Seunghee
AU - Panzer, Julia K.
AU - Caicedo, Alejandro
AU - Kusmartseva, Irina
AU - Posgai, Amanda L.
AU - Atkinson, Mark A.
AU - Albrecht, Randy A.
AU - García-Sastre, Adolfo
AU - Rosenberg, Brad R.
AU - Schotsaert, Michael
AU - Homann, Dirk
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/3/15
Y1 - 2022/3/15
N2 - 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.
AB - 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.
KW - COVID-19
KW - SARS-CoV-2
KW - human coronaviruses
KW - human islets
KW - pancreas
KW - type 1 diabetes
KW - type 2 diabetes
KW - viral infection
UR - http://www.scopus.com/inward/record.url?scp=85125720990&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2022.110508
DO - 10.1016/j.celrep.2022.110508
M3 - Article
C2 - 35247306
AN - SCOPUS:85125720990
SN - 2211-1247
VL - 38
JO - Cell Reports
JF - Cell Reports
IS - 11
M1 - 110508
ER -