Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19.

Diabetes is associated with increased mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2), the key entry factor for SARS-CoV-2 infection. Specifically, we analyzed five public scRNA-seq pancreas datasets and performed fluorescence in situ hybridization, western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) cases. These in silico and ex vivo analyses demonstrated prominent expression of ACE2 in pancreatic ductal epithelium and microvasculature, but we found rare endocrine cell expression at the mRNA level. Pancreata from individuals with COVID-19 demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression that was primarily limited to ducts. These results suggest SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, is an unlikely central pathogenic feature of COVID-19-related diabetes.

Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly across the USA, causing extensive morbidity and mortality, particularly in the African American community. Autopsy can considerably contribute to our understanding of many disease processes and could provide crucial information to guide management of patients with coronavirus disease 2019 (COVID-19). We report on the relevant cardiopulmonary findings in, to our knowledge, the first autopsy series of ten African American decedents, with the cause of death attributed to COVID-19. METHODS: Autopsies were performed on ten African American decedents aged 44-78 years with cause of death attributed to COVID-19, reflective of the dominant demographic of deaths following COVID-19 diagnosis in New Orleans. Autopsies were done with consent of the decedents' next of kin. Pulmonary and cardiac features were examined, with relevant immunostains to characterise the inflammatory response, and RNA labelling and electron microscopy on representative sections. FINDINGS: Important findings include the presence of thrombosis and microangiopathy in the small vessels and capillaries of the lungs, with associated haemorrhage, that significantly contributed to death. Features of diffuse alveolar damage, including hyaline membranes, were present, even in patients who had not been ventilated. Cardiac findings included individual cell necrosis without lymphocytic myocarditis. There was no evidence of secondary pulmonary infection by microorganisms. INTERPRETATION: We identify key pathological states, including thrombotic and microangiopathic pathology in the lungs, that contributed to death in patients with severe COVID-19 and decompensation in this demographic. Management of these patients should include treatment to target these pathological mechanisms. FUNDING: None.

Impact of telavancin on prothrombin time and activated partial thromboplastin time as determined using point-of-care coagulometers.

Telavancin is approved in the United States, Canada, and Europe (At the time of submission, the telavancin European marketing authorization for nosocomial pneumonia was suspended until Theravance provides evidence of a new European Medicines Agency approved supplier) as an antibiotic to treat certain Gram-positive bacterial skin infections. Telavancin has been shown to prolong plasmatic prothrombin (PT) and activated partial thromboplastin (aPTT) clotting times in clinical diagnostic lab-based assays. In this study, we evaluated the potential for telavancin to prolong whole blood PT/International Normalized Ratio (INR) and aPTT tests on point-of-care (POC) instruments. Whole blood collected from 8 healthy subjects was supplemented with telavancin to final concentrations of 0, 10, 20, and 100 µg/ml. Final concentrations were selected to match trough, twice trough, and peak plasma levels following the approved 10 mg/kg dose. Four widely employed POC coagulation instruments were chosen to be representative of the POC platforms currently in use.. These systems were the Roche Coaguchek XS, the Abbott iSTAT, the ITC Hemochron SIG+, and the Alere INRatio2 POC devices. The PT/INR measured by the Coaguchek XS showed the greatest sensitivity to the presence of telavancin. The PT/INR measured by the Hemochron SIG+ and iSTAT were sensitive to telavancin but to a lesser extent. The INRatio2 was the least sensitive to the presence of telavancin when testing the whole blood PT/INR. Only the Hemochron SIG+ device was capable of measuring aPTT and showed a concentration-dependent increase in aPTT. This study supports the current recommendation that PT and aPTT monitoring be conducted immediately to the next dose of telavancin when coagulation parameters are tested using POC instrumentation.