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Showing content from https://pubmed.ncbi.nlm.nih.gov/32299776/ below:

Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases

Microscopic features of pulmonary autopsy…

Microscopic features of pulmonary autopsy samples from Case 1. A, Significant fibrin deposition…

Microscopic features of pulmonary autopsy samples from Case 1. A, Significant fibrin deposition within the interalveolar septa and alveolar spaces, accompanied by marked hemorrhage and hemosiderin deposition. (Hematoxylin and eosin stain, 200×). B, Prominent destructive septal capillary injury is apparent, with fibrinoid necrosis of the capillaries accompanied by evidence of vascular compromise, with hemorrhage and fibrin and hemosiderin deposition within alveolar spaces. (Hematoxylin and eosin stain, 400×). C, Septal capillary injury is a pauci-inflammatory response. (Hematoxylin and eosin, 1000×). D, The septal capillary injury includes an interstitial and intra-alveolar accumulation of neutrophils. (Hematoxylin and eosin, 400×).

Immunohistochemistry analysis of pulmonary autopsy…

Immunohistochemistry analysis of pulmonary autopsy samples from Case 1. A, Extensive C4d deposition…

Immunohistochemistry analysis of pulmonary autopsy samples from Case 1. A, Extensive C4d deposition is seen throughout the lung parenchyma, with striking septal capillary localization. (Diaminobenzidene stain, 200×). B, Higher power magnification documents a clear localization of C4d within septal capillaries. (Diaminobenzidene, 1000×). C, A similar septal capillary distribution for C5b-9 deposition is observed, although it is less pronounced than that observed for C4d. (Diaminobenzidene, 1000×). D, A similar septal capillary distribution of C3d staining is observed, although it is also less pronounced than was observed for C4d. (Diaminobenzidene, 1000×).

Microscopic features of pulmonary autopsy…

Microscopic features of pulmonary autopsy samples from Case 2. A, Extensive hemorrhagic pneumonitis…

Microscopic features of pulmonary autopsy samples from Case 2. A, Extensive hemorrhagic pneumonitis was seen, with red cell extravasation and fibrin in alveolar spaces and luminal and mural fibrin deposition within septal capillaries. (Hematoxylin and eosin, 200×). B, The septa exhibit a pauci-cellular pattern of capillary injury as evidenced by significant fibrin deposition, with thrombi seen in capillaries. There is red cell extravasation in the alveolar spaces along with collections of neutrophils and monocytes. (Hematoxylin and eosin, 400×). C, There is slight widening of the septa by a few inflammatory cells, predominantly neutrophils. There is evidence of capillary injury characterized by fibrin deposition in the lumens and walls with red cell extravasation within the septa and adjacent alveolar space. Type II pneumocyte hyperplasia and viral cytopathic effects are not discernible. (Hematoxylin and eosin, 400×). D, Higher power examination further illuminates capillary wall disruption accompanied by fibrin deposition and red cell extravasation, with neutrophils in the septa and within the alveolar spaces. (Hematoxylin and eosin, 1000×).

Immunohistochemistry analysis of pulmonary autopsy…

Immunohistochemistry analysis of pulmonary autopsy samples from Case 2. A, There was striking…

Immunohistochemistry analysis of pulmonary autopsy samples from Case 2. A, There was striking deposition of C5b-9 within the microvasculature of the interalveolar septa. (Diaminobenzidene, 200×). B, Higher power magnification again shows localization of C5b-9 within the septa, including C5b-9 deposits in areas of normal appearing lung, suggestive of systemic complement activation. (Diaminobenizdene, 1000×). C, C4d deposition was largely localized to the interalveolar septa in areas of microvascular injury. (Diaminobenzidene 400×). D, A higher power image demonstrates the extensive degree of C4d deposition within the septa. (Diaminobenzidene, 1000×). E, MASP2 staining showed granular and punctate deposits localized to the interalveolar septa.

Clinical, microscopic, and immunhohistochemical analyses…

Clinical, microscopic, and immunhohistochemical analyses of Case 3. A, Striking retiform purpura with…

Clinical, microscopic, and immunhohistochemical analyses of Case 3. A, Striking retiform purpura with surrounding inflammation was noted on the buttocks. B, Skin biopsy showed an extensive pattern of pauci-inflammatory vascular thrombosis with endothelial cell injury. (Hematoxylin and eosin, 400×). C, Prominent deposits of C5b-9 are seen within the microvasculature. (Diaminobenzidene, 400×).

Clinical, microscopic, and immunhohistochemical analyses…

Clinical, microscopic, and immunhohistochemical analyses of Case 4. A, Prominent livedo rashes on…

Clinical, microscopic, and immunhohistochemical analyses of Case 4. A, Prominent livedo rashes on the palmar and plantar aspects of the hands and feet, respectively, were noted. B, Skin biopsy demonstrated an occlusive arterial thrombus within deeper dermis. (Hematoxylin and eosin, 200×). C, Extensive endothelial and subendothelial deposits of C5b-9 are observed within the thrombosed artery. (Diaminobenzidene, 400×). D, A similar striking pattern of endothelial and subendothelial C4d deposition is noted within the artery. (Diaminobenzidene, 400×). E, A biopsy of normal-appearing deltoid skin showing conspicuous microvascular deposits of C5b-9. (Diaminobenzidene, 400×).

Clinical, microscopic, and immunhohistochemical analyses…

Clinical, microscopic, and immunhohistochemical analyses of Case 5. A, A lacey livedoid rash…

Clinical, microscopic, and immunhohistochemical analyses of Case 5. A, A lacey livedoid rash on the lower extremities was noted. B, A skin biopsy revealed a few deep-seated venules at the dermal-subcuticular interface containing small fibrin thrombi. (Hematoxylin and eosin, 400×). C, There are significant vascular deposits of C5b-9 within the dermis. (Diaminobenzidene, 400×). D, Vascular deposits of C4d were also observed within the dermal microvasculature. (Diaminobenzidene, 400×). E, A biopsy of normal-appearing deltoid skin shows microvascular deposits of C5b-9. (Diaminobenzidene, 400×).

Demonstration of co-localization of complement…

Demonstration of co-localization of complement components with SARS-CoV2 spike glycoprotein in the lung…

Demonstration of co-localization of complement components with SARS-CoV2 spike glycoprotein in the lung of Case 1. A, Striking deposition of C4d within the interalveolar septa of the lung was first demonstrated by DAB staining. Using NUANCE software the C4d image appears green (B) while the SARS-CoV2 spike protein appears red (C). D, A merged image shows a significant degree of C4d and SARS-CoV2 co-localization, as revealed by intense yellow staining. E–H, A similar pattern was observed using an anti-C5b-9 reagent whose image appears green, with a significant degree of C5b-9 and SARS-CoV2 co-localization, as revealed by intense yellow staining.

Demonstration of co-localization of C4d…

Demonstration of co-localization of C4d and SARS-CoV2 spike glycoprotein in the skin of…

Demonstration of co-localization of C4d and SARS-CoV2 spike glycoprotein in the skin of Case 3. A, The skin biopsy was stained for C4d showing significant vascular localization (DAB stain). B, Using NUANCE software C4d is highlighted green while COVID-19 spike protein shows a red staining pattern; a yellow signal is discernible indicative of co-localization of C4d and viral protein within the microvasculature.

Model for AP and LP…

Model for AP and LP complement activation by SARS-CoV2, and its interaction with…

Model for AP and LP complement activation by SARS-CoV2, and its interaction with coagulation cascades.

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