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Preprint in English | MEDLINE | ID: ppcovidwho-326588


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 beta cells. This would require binding and entry of SARS-CoV-2 into host beta 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 alpha or beta 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 beta cells through these cell entry proteins.

Journal of the American Society of Nephrology ; 31:298, 2020.
Article in English | EMBASE | ID: covidwho-984436


Background: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to coronavirus disease 2019 (COVID-19) has predominantly resulted in a profound hypoxic respiratory disease with a significant subset of patients demonstrating abnormalities in renal function. Acute kidney injury (AKI) in these patients is an independent risk factor for mortality;however, the mechanism for injury is unknown and our understanding of the pathologic findings is limited. Methods: Kidney tissue from nine patients who died with COVID-19 was obtained at autopsy and evaluated by light, immunofluorescence, and electron microscopy. RNAScope technology was used to perform RNA in situ hybridization (RNA ISH) with probes to the SARS-CoV-2 virus (sense) and for human gene ACE2. Results: The cohort was comprised of 6 men and 3 women, 78% black, median age of 65 years (37 - 78) and median body mass index 29 (26 - 48) kg/m2, of which 6 (67%) had hypertension and 4 (44%) had diabetes. AKI was present in 7 of 9 (78%), 5 (55%) of them needed dialysis. One patient had creatine kinase about 5000 U/L suggestive of rhabdomyolysis. All but one expired while on mechanical ventilation. The predominant morphologic finding on postmortem biopsy was acute tubular injury. Three cases (33%) demonstrated endocapillary platelet aggregates with one demonstrating fibrin tactoids and loss of endothelial fenestrations by EM, consistent with early TMA;however, no overt thrombotic microangiopathy was present. Immunofluorescence in one case demonstrated mesangial C3 staining without deposits by EM. Background mild-to-moderate arterionephrosclerosis was present in 6 of 9 (67%) cases. In one patient with AKI at time of death, RNA-ISH detected SARS-CoV-2 in tubular epithelial cells which also express ACE2, the receptor for coronavirus cell entry. Conclusions: Among a cohort of 9 patients dying with COVID-19, postmortem evaluation of kidney samples predominantly revealed ATI without overt evidence of hypercoaguloability, complement dysregulation, or immune complex deposition. While the mechanism for AKI in most cases is not immediately apparent, this series suggests, but does not prove, direct renal infection with SARS-CoV-2 as the presence of viral RNA does not prove active viral infection.