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 - Funding Information:
We thank the families of the organ donors for the gift of tissues. We would like to acknowledge the expertise and assistance of the Dean’s Flow Cytometry CORE at Mount Sinai as well as Jill Gregory, who designed the graphical abstract, printed here with permission from Mount Sinai Health System. These efforts were supported by JDRF 3-PDF-2018-575-A-N (to V.v.d.H.); NIH / NIDDK R01DK12392 , NIH / NIAID P01AI042288 , and NIH / NIAID U54AI142766-S1 (to M.A.A.); NIH / NIAID Center of Excellence for Influenza Research and Response/Center for Research for Influenza Pathogenesis and Transmission contract 75N93019R00028 , NIH / NIAID U19AI135972 (supplement), Defense Advanced Research Projects Agency HR0011-19-2-0020 , the JPB Foundation , and Open Philanthropy Project 2020-215611 (5384) , Anonymous (to A.G.-S.); NIH / NIAID R01AI151029 and NIH / NIAID U01AI150748 (to B.R.R.); NIH / NIDDK R01DK130425 (to M.S.); and NIH / NIAID R01AI134971 , NIH / NIDDK U01DK123716 , NIH / NIDDK U01DK104162 , NIH / NIDDK P30DK020541 , and NIH / NIDDK R01DK130425 (to D. Homann). The funders had no role in study design, data collection, and interpretation, nor the decision to submit the work for publication.
Funding Information:
We thank the families of the organ donors for the gift of tissues. We would like to acknowledge the expertise and assistance of the Dean's Flow Cytometry CORE at Mount Sinai as well as Jill Gregory, who designed the graphical abstract, printed here with permission from Mount Sinai Health System. These efforts were supported by JDRF 3-PDF-2018-575-A-N (to V.v.d.H.); NIH/NIDDK R01DK12392, NIH/NIAID P01AI042288, and NIH/NIAID U54AI142766-S1 (to M.A.A.); NIH/NIAID Center of Excellence for Influenza Research and Response/Center for Research for Influenza Pathogenesis and Transmission contract 75N93019R00028, NIH/NIAID U19AI135972 (supplement), Defense Advanced Research Projects Agency HR0011-19-2-0020, the JPB Foundation, and Open Philanthropy Project 2020-215611 (5384), Anonymous (to A.G.-S.); NIH/NIAID R01AI151029 and NIH/NIAID U01AI150748 (to B.R.R.); NIH/NIDDK R01DK130425 (to M.S.); and NIH/NIAID R01AI134971, NIH/NIDDK U01DK123716, NIH/NIDDK U01DK104162, NIH/NIDDK P30DK020541, and NIH/NIDDK R01DK130425 (to D. Homann). The funders had no role in study design, data collection, and interpretation, nor the decision to submit the work for publication. Conceptualization and project administration, V.v.d.H. M.S. and D. Homann.; methodology, V.v.d.H. (viruses/infections and flow cytometry), S.J. (viruses/infections), R.R. (viruses/infections), T.A. (viruses/infections), R.A.A. (viruses/infections), M.S. (viruses/infections), A.R. (mass cytometry), I.K. (pancreas slices), J.K.P. (pancreas slices), A.C. (pancreas slices), A.G.-S. (viruses/infections), and D. Homann (mass cytometry and flow cytometry); investigation, V.v.d.H. (viruses/infections, flow cytometry, and pancreas slices), S.J. (viruses/infections and pancreas slices), R.R. (viruses/infections), S.A. (viruses/infections), T.A. (viruses/infections), R.A.A. (viruses/infections), M.S. (viruses/infections), T.D. (scRNA-seq), J.Q. (scRNA-seq), D.D. (scRNA-seq), D. Handler (mass cytometry), G.K. (mass cytometry), B.L. (mass cytometry), and D. Homann (flow cytometry); software, P.C. (scRNA-seq analysis) and B.R.R. (scRNA-seq analysis); data curation and formal analysis, V.v.d.H. S.J. P.C. B.R.R. M.S. and D. Homann; resources, B.R.R. M.S. A.G.-S. M.A.A. R.A.A. S.K.-S. and D. Homann; writing ? original draft, V.v.d.H. and D. Homann; writing ? review & editing, all authors; visualization, V.v.d.H. A.L.P. and D. Homann; supervision, M.S. and D. Homann; funding acquisition, V.v.d.H. M.A.A. A.G.-S. B.R.R. M.S. and D. Homann. The A.G.-S. laboratory has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, and Merck outside of the reported work. A.G.-S. has consulting agreements outside of the reported work for the following companies, involving cash and/or stock: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, and Pfizer. A.G.-S. is an inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. One or more of the authors of this paper received support from a program designed to increase minority representation in science. The author list of this paper includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.
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 -