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1.
Cell Metab ; 32(6): 1028-1040.e4, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-1310646

ABSTRACT

Isolated reports of new-onset diabetes in individuals with COVID-19 have led to the hypothesis that SARS-CoV-2 is directly cytotoxic to pancreatic islet ß cells. This would require binding and entry of SARS-CoV-2 into ß cells via co-expression of its canonical cell entry factors, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2); however, their expression in human pancreas has not been clearly defined. We analyzed six transcriptional datasets of primary human islet cells and found that ACE2 and TMPRSS2 were not co-expressed in single ß cells. In pancreatic sections, ACE2 and TMPRSS2 protein was not detected in ß cells from donors with and without diabetes. Instead, ACE2 protein was expressed in islet and exocrine tissue microvasculature and in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. These findings reduce the likelihood that SARS-CoV-2 directly infects ß cells in vivo through ACE2 and TMPRSS2.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Diabetes Mellitus/metabolism , SARS-CoV-2/physiology , Serine Endopeptidases/metabolism , Virus Internalization , Angiotensin-Converting Enzyme 2/analysis , Angiotensin-Converting Enzyme 2/genetics , Animals , COVID-19/complications , COVID-19/genetics , Cells, Cultured , Diabetes Complications/genetics , Diabetes Complications/metabolism , Diabetes Mellitus/genetics , Gene Expression , Humans , Insulin-Secreting Cells/metabolism , Mice , Microvessels/metabolism , Pancreas/metabolism , RNA, Messenger/analysis , RNA, Messenger/genetics , Serine Endopeptidases/analysis , Serine Endopeptidases/genetics
2.
bioRxiv ; 2020 Oct 20.
Article in English | MEDLINE | ID: covidwho-955725

ABSTRACT

Reports of new-onset diabetes and diabetic ketoacidosis in individuals with COVID-19 have led to the hypothesis that SARS-CoV-2, the virus that causes COVID-19, is directly cytotoxic to pancreatic islet ß cells. This would require binding and entry of SARS-CoV-2 into host ß cells via cell surface co-expression of ACE2 and TMPRSS2, the putative receptor and effector protease, respectively. To define ACE2 and TMPRSS2 expression in the human pancreas, we examined six transcriptional datasets from primary human islet cells and assessed protein expression by immunofluorescence in pancreata from donors with and without diabetes. ACE2 and TMPRSS2 transcripts were low or undetectable in pancreatic islet endocrine cells as determined by bulk or single cell RNA sequencing, and neither protein was detected in α or ß cells from these donors. Instead, ACE2 protein was expressed in the islet and exocrine tissue microvasculature and also found in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. The absence of significant ACE2 and TMPRSS2 co-expression in islet endocrine cells reduces the likelihood that SARS-CoV-2 directly infects pancreatic islet ß cells through these cell entry proteins.

3.
Nepal Journal of Dermatology, Venereology & Leprology ; 18(1):3-8, 2020.
Article in English | Nepal Journals Online | ID: covidwho-926868

ABSTRACT

Introduction: Novel Coronavirus disease has caused a substantial halt to the ongoing world in every aspect. There are medical and social implications of the disease. Cutaneous manifestations have been reported to be a part of the disease as well. Dermatologists globally are in dilemma with the clinical practice because of the fear of acquiring the disease. Objectives: This article aims to recommend best practice measures that can be followed in local scenario for re-opening up of dermatological services in the context of Nepal. Materials and Methods: A preliminary draft for guidance on Dermatological services based on recommendations of American Academy of Dermatology, International league of Dermatological societies, National recommendations from Ministry of Health, Nepal was sent to a panel of national experts to determine the level of consensus in first week of April, 2020.  A preliminary survey was sent to all the members of Society of Dermatologists, Venereologists, and leprologists of Nepal on first week of June and a second draft was subsequently formed which was sent again to experts and revised based on the opinions of national experts. Results: A total of 19 experts participated in the preparation of draft and reached a national consensus after a series of revisions in preliminary draft. Conclusion: Agreements regarding the opening of practice in dermatology discipline have been summarized. Recommendations have been made for opening of dermatological services – opening of outpatient department, performing dermatosurgical and cosmetic procedures as well as strategies on triage of patients and use of masks.

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