Home Nephro News Electron Microscopic Investigations in COVID-19: Not all Crowns Are Coronas

Electron Microscopic Investigations in COVID-19: Not all Crowns Are Coronas

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Large image of Figure 1.

Renal involvement, in the form of acute kidney injury, haematuria and/or proteinuria, is common in patients with COVID-19 (1x1Cheng, Y., Luo, R., Wang, K. et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020;
97: 829–838
Abstract | Full Text | Full Text PDF | PubMed | Scopus (17)
| Google ScholarSee all References
). Post-mortem renal histology has shown acute tubular injury, microvascular thrombi and inflammation (2x2Diao B, Wang C, Wang R, et al. Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection. medRxiv2020;; https://doi.org/10.1101/2020.03.04.20031120
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,3x3Varga, S., Flammer, A., Steiger, P. et al. Endothelial cell infection and endotheliitis in COVID-19. The Lancet. 2020;
()
Abstract | Full Text | Full Text PDF | Scopus (5)
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,4x4Su, H., Yang, M., Wan, C. et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int. 2020;
https://doi.org/10.1016/j.kint.2020.04.003
Abstract | Full Text | Full Text PDF | Scopus (3)
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,5x5Farkash, E., Wilson, A., and Jentzen, J. Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2. J Am Soc Nephrol. 2020;
https://doi.org/10.1681/ASN.2020040432
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); collapsing focal and segmental glomerulosclerosis has been reported in live patient biopsies (6x6Kissling, S., Rotman, S., Gerber, C. et al. Collapsing glomerulopathy in a COVID-19 patient. Kidney Int. 2020;
https://doi.org/10.1016/j.kint.2020.04.006
Abstract | Full Text | Full Text PDF
| Google ScholarSee all References
). The pathogenesis of renal injury remains unclear. Direct viral cytopathic injury is possible, due to expression of viral receptor ACE2 on tubular epithelial cells. Indirect immunological and/or pro-thrombotic infection-related effects may also be at play. Using electron microscopy (EM), putative virions have been described in tubular epithelial cells (2x2Diao B, Wang C, Wang R, et al. Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection. medRxiv2020;; https://doi.org/10.1101/2020.03.04.20031120
Google ScholarSee all References
,4x4Su, H., Yang, M., Wan, C. et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int. 2020;
https://doi.org/10.1016/j.kint.2020.04.003
Abstract | Full Text | Full Text PDF | Scopus (3)
| Google ScholarSee all References
,5x5Farkash, E., Wilson, A., and Jentzen, J. Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2. J Am Soc Nephrol. 2020;
https://doi.org/10.1681/ASN.2020040432
Crossref | Scopus (0)
| Google ScholarSee all References
), endothelial cells (3x3Varga, S., Flammer, A., Steiger, P. et al. Endothelial cell infection and endotheliitis in COVID-19. The Lancet. 2020;
()
Abstract | Full Text | Full Text PDF | Scopus (5)
| Google ScholarSee all References
) and podocytes (6x6Kissling, S., Rotman, S., Gerber, C. et al. Collapsing glomerulopathy in a COVID-19 patient. Kidney Int. 2020;
https://doi.org/10.1016/j.kint.2020.04.006
Abstract | Full Text | Full Text PDF
| Google ScholarSee all References
). We performed EM on 3 biopsies from live patients with COVID-19 from different centres, and found similar images to those reported in the literature [Fig 1, A,E,F,I]. Consultation amongst renal pathologists, electron microscopists and virologists concluded that the intracellular structures represented clathrin-coated vesicles (CC) and microvesicular bodies (MVB), whereas the extracellular structures represented extruded microvesicles from MVB and degenerate microvilli. Examination of biopsies taken in 2019, preceding the emergence of SARS-CoV-2, revealed identical structures [Fig 1, B,G,J]. MVBs and CCs are both part of the endosomal pathway. MVBs may fuse with lysosomes and autophagosomes leading to variable appearances. CCs arise from clathrin-coated pits; their clathrin coat resembles a crown on EM. Electron microscopy has an important role to play in elucidating the pathogenesis of COVID-19, along with identification of viral RNA or proteins, but images need to show features that are clearly distinct from viral look-a-like subcellular structures.

Figure 1

A. Transplant patient 2 weeks post-positive nasal swab for SARS-CoV2, with graft dysfunction and borderline for T-cell mediated rejection on biopsy; endothelial cell containing a microvesicular structure with a “corona”, 65 nm in diameter (white arrow, scale bar 100nm, magnification 20 000x). B. Transplant patient biopsied in August 2019 with graft dysfunction and borderline for T-cell mediated rejection on biopsy, showing an endothelial cell containing identical structures (scale bar 100nm, white arrow, magnification 20 000x). C. Clathrin-coated pits (arrowhead, CCP) at the plasma membrane (renal proximal tubular epithelial cells, scale bar 100nm). D. Clathrin-coated Intracytoplasmic vesicles (arrowhead, CC)(renal proximal tubular epithelial cells, scale bar 100nm). E. Native renal biopsy from a patient with COVID-19 and collapsing focal and segmental glomerulosclerosis; podocyte containing a microvesicular body/autophagosome (scale bar 100nm, magnification 98 000x). F. Same patient as Fig 1A, microvesicular body in a podocyte (scale bar 100 nm, magnification 15 000x). G. Same patient as Fig 1B, microvesicular body in a podocyte (scale bar 100 nm, magnification 15 000x). H. Microvesicular bodies typical for adult human cell lines in culture (HeLa cells, scale bar 200nm). I. Same patient as Fig 1E, extracellular structures along the glomerular basement membrane with “corona” 42 to 70 nm in diameter, likely either extruded microvesicles or degenerate microvilli (scale bar 200 nm, magnification 68 000x). J. Patient with a native renal biopsy from December 2019, showing similar extracellular structures to Fig 1I in an ischaemic glomerulus (scale bar 200nm, magnification 68 000x)

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