Acute Endotheliitis (Type 3 Hypersensitivity Vasculitis) in Ten COVID-19 Autopsy Brains

Central nervous system (CNS) involvement in COVID-19 may occur through direct SARS-CoV-2 invasion through peripheral or cranial nerves or through vascular endothelial cell infection. The renin-angiotensin system may play a major part in CNS morbidity. Effects of hypoxia have also been implicated in CNS lesions in COVID-19. This communication reports on ten consecutive autopsies of individuals with death due to COVID-19 with decedent survival ranging from 30 minutes to 84 days after admission. All ten brains examined had neutrophilic microvascular endotheliitis present in variable amounts and variably distributed. Importantly, this acute stage of type 3 hypersensitivity vasculitis can be followed by fibrinoid necrosis and inner vascular wall sclerosis, but these later stages were not found. These results suggest that a vasculitis with autoimmune features occurred in all ten patients. It is possible that viral antigen in or on microvascular walls or other antigen-antibody complexes occurred in all ten patients proximate to death as a form of autoimmune vasculitis.

ACE2 and SARS-CoV-2 Expression in the Normal and COVID-19 Pancreas

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 the key molecule for SARS-CoV-2 infection of cells, angiotensin-converting enzyme-2 (ACE2). Specifically, we analyzed five public scRNAseq 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) patients. These in silico and ex vivo analyses demonstrated pancreatic expression of ACE2 is prominent in pancreatic ductal epithelium and the microvasculature, with rare endocrine cell expression of this molecule. Pancreata from COVID-19 patients demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression primarily limited to ducts. SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, appears an unlikely central pathogenic feature of COVID-19 as it relates to diabetes.

Multiscale three-dimensional pathology findings of COVID-19 diseased lung using high-resolution cleared tissue microscopy

The study of pulmonary samples from individuals who have died as a direct result of COVID-19 infection is vital to our understanding of the pathogenesis of this disease. Histopathologic studies of lung tissue from autopsy of patients with COVID-19 specific mortality are only just emerging. All existing reports have relied on traditional 2-dimensional slide-based histological methods for specimen preparation. However, emerging methods for high-resolution, massively multiscale imaging of tissue microstructure using fluorescence labeling and tissue clearing methods enable the acquisition of tissue histology in 3-dimensions, that could open new insights into the nature of SARS-Cov-2 infection and COVID-19 disease processes. In this article, we present the first 3-dimensional images of lung autopsy tissues taken from a COVID-19 patient, including 3D "virtual histology" of cubic-millimeter volumes of the diseased lung, providing unique insights into disease processes contributing to mortality that could inform frontline treatment decisions.

Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series from New Orleans

SARS-CoV-2 has rapidly spread across the United States, causing extensive morbidity and mortality, though the histopathologic basis of severe disease cases has yet to be studied in detail. Over the past century, autopsy has contributed significantly to our understanding of numerous disease processes, but for several reasons, autopsy reports following deaths related to SARS- CoV-2 have thus far been limited across the globe. We report on the relevant cardiopulmonary findings in the first series of autopsies in the United States, with the cause of death being due to SARS-CoV-2 infection. These cases identify key pathologic states potentially contributing to severe disease and decompensation in these patients.