%0 Journal Article %1 magro2021severe %A Magro, Cynthia M. %A Mulvey, Justin %A Kubiak, Jeffrey %A Mikhail, Sheridan %A Suster, David %A Crowson, A. Neil %A Laurence, Jeffrey %A Nuovo, Gerard %D 2021 %J Annals of Diagnostic Pathology %K covid-19 ivermectin spike %P 151645 %R https://doi.org/10.1016/j.anndiagpath.2020.151645 %T Severe COVID-19: A multifaceted viral vasculopathy syndrome %U https://www.sciencedirect.com/science/article/pii/S109291342030191X %V 50 %X The objective of this study was to elucidate the pathophysiology that underlies severe COVID-19 by assessing the histopathology and the in situ detection of infectious SARS-CoV-2 and viral capsid proteins along with the cellular target(s) and host response from twelve autopsies. There were three key findings: 1) high copy infectious virus was limited mostly to the alveolar macrophages and endothelial cells of the septal capillaries; 2) viral spike protein without viral RNA localized to ACE2+ endothelial cells in microvessels that were most abundant in the subcutaneous fat and brain; 3) although both infectious virus and docked viral spike protein was associated with complement activation, only the endocytosed pseudovirions induced a marked up-regulation of the key COVID-19 associated proteins IL6, TNF alpha, IL1 beta, p38, IL8, and caspase 3 in endothelium. Importantly, this microvasculitis was associated with characteristic findings on hematoxylin and eosin examination that included endothelial degeneration and resultant basement membrane zone disruption and reduplication. It is concluded that serious COVID-19 infection has two distinct mechanisms: 1) a microangiopathy of pulmonary capillaries associated with a high infectious viral load where endothelial cell death releases pseudovirions into the circulation, and 2) the pseudovirions dock on ACE2+ endothelial cells most prevalent in the skin/subcutaneous fat and brain that activates the complement pathway/coagulation cascade resulting in a systemic procoagulant state as well as endothelial expression of cytokines that produce the cytokine storm. The data predicts a favorable response to therapies based on either removal of circulating viral proteins and/or blunting of the endothelial-induced response.

@article{magro2021severe, abstract = {The objective of this study was to elucidate the pathophysiology that underlies severe COVID-19 by assessing the histopathology and the in situ detection of infectious SARS-CoV-2 and viral capsid proteins along with the cellular target(s) and host response from twelve autopsies. There were three key findings: 1) high copy infectious virus was limited mostly to the alveolar macrophages and endothelial cells of the septal capillaries; 2) viral spike protein without viral RNA localized to ACE2+ endothelial cells in microvessels that were most abundant in the subcutaneous fat and brain; 3) although both infectious virus and docked viral spike protein was associated with complement activation, only the endocytosed pseudovirions induced a marked up-regulation of the key COVID-19 associated proteins IL6, TNF alpha, IL1 beta, p38, IL8, and caspase 3 in endothelium. Importantly, this microvasculitis was associated with characteristic findings on hematoxylin and eosin examination that included endothelial degeneration and resultant basement membrane zone disruption and reduplication. It is concluded that serious COVID-19 infection has two distinct mechanisms: 1) a microangiopathy of pulmonary capillaries associated with a high infectious viral load where endothelial cell death releases pseudovirions into the circulation, and 2) the pseudovirions dock on ACE2+ endothelial cells most prevalent in the skin/subcutaneous fat and brain that activates the complement pathway/coagulation cascade resulting in a systemic procoagulant state as well as endothelial expression of cytokines that produce the cytokine storm. The data predicts a favorable response to therapies based on either removal of circulating viral proteins and/or blunting of the endothelial-induced response.}, added-at = {2021-07-28T14:44:15.000+0200}, author = {Magro, Cynthia M. and Mulvey, Justin and Kubiak, Jeffrey and Mikhail, Sheridan and Suster, David and Crowson, A. Neil and Laurence, Jeffrey and Nuovo, Gerard}, biburl = {https://www.bibsonomy.org/bibtex/2ffb93ec1e1302482a2a8ec60079c300d/fordham1}, description = {Severe COVID-19: A multifaceted viral vasculopathy syndrome - ScienceDirect}, doi = {https://doi.org/10.1016/j.anndiagpath.2020.151645}, interhash = {db99084fc2f232e3dc325ac089a22c54}, intrahash = {ffb93ec1e1302482a2a8ec60079c300d}, issn = {1092-9134}, journal = {Annals of Diagnostic Pathology}, keywords = {covid-19 ivermectin spike}, pages = 151645, timestamp = {2021-07-28T14:44:15.000+0200}, title = {Severe COVID-19: A multifaceted viral vasculopathy syndrome}, url = {https://www.sciencedirect.com/science/article/pii/S109291342030191X}, volume = 50, year = 2021 }