Electron microscopic investigations in COVID-19: not all crowns are coronas
Authors: Candice Roufosse, Elizabeth Curtis, Linda Moran, Michael Hollinshead, Terry Cook, Brian Hanley, Catherine Horsfield, Desley Neil
Journal: Kidney International (2020)

Renal involvement, in the form of acute kidney injury, hematuria, and/or proteinuria, is common in patients with coronavirus disease 2019 (COVID-19).1Cheng Y. Luo R. Wang K. et al.Kidney disease is associated with in-hospital death of patients with COVID-19.Kidney Int. 2020; 97: 829-838Abstract Full Text Full Text PDF PubMed Scopus (1932) Google Scholar Postmortem renal histology has shown acute tubular injury, microvascular thrombi, and inflammation2Diao 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/10.1101/2020.03.04.20031120Google Scholar, 3Varga S. Flammer A. Steiger P. et al.Endothelial cell infection and endotheliitis in COVID-19.Lancet. 2020; 395: 1417-1418Abstract Full Text Full Text PDF PubMed Scopus (4567) Google Scholar, 4Su H. Yang M. Wan C. et al.Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China.Kidney Int. 2020; 98: 219-227Abstract Full Text Full Text PDF PubMed Scopus (1291) Google Scholar, 5Farkash E, Wilson A, Jentzen J. Ultrastructural evidence for direct renal infection with SARS-CoV-2 [e-pub ahead of print]. J Am Soc Nephrol. http://doi.org/10.1681/ASN.2020040432. Accessed May 6, 2020.Google Scholar; collapsing focal and segmental glomerulosclerosis has been reported in live patient biopsies.6Kissling S. Rotman S. Gerber C. et al.Collapsing glomerulopathy in a COVID-19 patient.Kidney Int. 2020; 98: 228-231Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar The pathogenesis of renal injury remains unclear. Direct viral cytopathic injury is possible, due to expression of viral receptor angiotensin-converting enzyme 2 (ACE2) on tubular epithelial cells. Indirect immunologic and/or prothrombotic infection-related effects may also be at play. Using electron microscopy, putative virions have been described in tubular epithelial cells,2Diao 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/10.1101/2020.03.04.20031120Google Scholar,4Su H. Yang M. Wan C. et al.Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China.Kidney Int. 2020; 98: 219-227Abstract Full Text Full Text PDF PubMed Scopus (1291) Google Scholar,5Farkash E, Wilson A, Jentzen J. Ultrastructural evidence for direct renal infection with SARS-CoV-2 [e-pub ahead of print]. J Am Soc Nephrol. http://doi.org/10.1681/ASN.2020040432. Accessed May 6, 2020.Google Scholar endothelial cells,3Varga S. Flammer A. Steiger P. et al.Endothelial cell infection and endotheliitis in COVID-19.Lancet. 2020; 395: 1417-1418Abstract Full Text Full Text PDF PubMed Scopus (4567) Google Scholar and podocytes.6Kissling S. Rotman S. Gerber C. et al.Collapsing glomerulopathy in a COVID-19 patient.Kidney Int. 2020; 98: 228-231Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar We performed electron microscopy on 3 biopsies from live patients with COVID-19, from different centers, and found images similar to those reported in the literature (Figure 1a, e, f, and i). Consultation among renal pathologists, electron microscopists, and virologists led to the conclusion that the intracellular structures represented clathrin-coated vesicles and microvesicular bodies, whereas the extracellular structures represented extruded microvesicles from microvesicular bodies and degenerate microvilli (Figure 1c, d, and h). Examination of biopsies taken in 2019, preceding the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), revealed identical structures (Figure 1b, g, and j). Microvesicular bodies and clathrin-coated vesicles are both part of the endosomal pathway. Microvesicular bodies may fuse with lysosomes and autophagosomes, leading to variable appearances. Clathrin-coated vesicles arise from clathrin-coated pits; their clathrin coat resembles a crown on electron microscopy. 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.