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• W3022743401 abstract "We read with concern the articles that report the presence of coronavirus in kidney based on electron microscopic evidence.1Su 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 (1197) Google Scholar,2Kissling 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 (225) Google Scholar Neither article, in fact, demonstrates the presence of coronavirus in the kidney. Su et al.1Su 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 (1197) Google Scholar show purported virus particles in the cytoplasm of kidney tubular epithelium and podocytes. These structures are not viral particles, but rather clathrin-coated vesicles, normal cell organelles involved in intracellular transport. The objects in their Figure 2a and b (∼60 nm) are somewhat smaller than coronaviruses (∼80 to 140+ nm), but more importantly, their “spikes” (peplomers) are in contact with the cytosol, as are those on clathrin-coated vesicles; the larger particle in Figure 2d also has spikes that are touching the cytosol and does not have dense dots inside the particles corresponding to the coiled nucleocapsid, cut in cross section. Coronaviruses, on the other hand, have their projections either facing the extracellular space between cells or the space inside vacuoles within the cells.3Goldsmith C.S. Tatti K.M. Ksiazek T.G. et al.Ultrastructural characterization of SARS coronavirus.Emerg Infect Dis. 2004; 10: 320-326Crossref PubMed Scopus (300) Google Scholar, 4Fehr A.R. Perlman S. Coronaviruses: an overview of their replication and pathogenesis.in: Maier H.J. Bickerton E. Britton P. Coronaviruses: Methods and Protocols. 1282. Springer, New York, NY2015: 1-23Crossref Scopus (160) Google Scholar, 5Miller S.E. Diagnosis of viral infection by electron microscopy.in: Lennette E.H. Lennette D.A. Lennette E.T. Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections. American Public Health Association, Washington, DC1995: 35-76Google Scholar This phenomenon is due to the fact that coronaviruses receive their outer covering by budding into or on cellular membranes, thereby forming intracellular vacuoles with the viral projections in contact with the vacuolar content, not the cytosol. During assembly, viral structural proteins are incorporated into the endoplasmic reticulum–Golgi complex of the infected cell, and viral RNA, packaged with another protein, buds into these membranes, forming a membrane-bound sac containing mature virions; the spikes are on the outside of the virion, but inside the vacuole and not in direct contact with the cytosol (Figure 1). These virions get out of the cell by exocytosis when the vacuole membrane fuses with the plasma membrane and opens its contents to the outside; thus, complete virions with peplomers are seen within the cell inside the membrane container (sequestered from the cytosol) and outside of cells, frequently still attached to the opened vacuolar membrane that has fused with the plasma membrane. The particles shown in electron micrographs in the article by Su et al.1Su 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 (1197) Google Scholar have their spikes in contact with the cytoplasmic fluid, like endocytotic vesicles, that is, clathrin-coated vesicles (see Plate 523, Figures 3–5, pp. 1214–1215 in Ghadially6Ghadially F.N. 4th ed. Ultrastructural Pathology of the Cell and Matrix. Vol. 2. Butterworth-Heinemann, Boston, MA1997Google Scholar; Figure 18c and d in Miller7Miller S.E. Detection and identification of viruses by electron microscopy.J Electron Microsc Tech. 1986; 4: 265-301Crossref PubMed Scopus (46) Google Scholar; and Miller8Miller S.E. Problems and pitfalls in diagnostic electron microscopy.Microsc Microanal. 2012; 18: 172-173Crossref Scopus (5) Google Scholar). Likewise, the particles in Kissling et al.2Kissling 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 (225) Google Scholar are not coronaviruses. While they are inside a vacuole, have spikes, and are approximately the correct size, they do not have the uniform appearance of virus particles with a membrane outer covering and dots inside indicating the nucleocapsid.3Goldsmith C.S. Tatti K.M. Ksiazek T.G. et al.Ultrastructural characterization of SARS coronavirus.Emerg Infect Dis. 2004; 10: 320-326Crossref PubMed Scopus (300) Google Scholar, 4Fehr A.R. Perlman S. Coronaviruses: an overview of their replication and pathogenesis.in: Maier H.J. Bickerton E. Britton P. Coronaviruses: Methods and Protocols. 1282. Springer, New York, NY2015: 1-23Crossref Scopus (160) Google Scholar, 5Miller S.E. Diagnosis of viral infection by electron microscopy.in: Lennette E.H. Lennette D.A. Lennette E.T. Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections. American Public Health Association, Washington, DC1995: 35-76Google Scholar These objects are inside a vesicle called a multivesicular body (see Plates 277–278, pp. 632–634 in Ghadially6Ghadially F.N. 4th ed. Ultrastructural Pathology of the Cell and Matrix. Vol. 2. Butterworth-Heinemann, Boston, MA1997Google Scholar; Calomeni et al.9Calomeni E. Satoskar A. Ayoub I. et al.Multivesicular bodies mimicking SARS-CoV-2 in patients without COVID-19.Kidney Int. 2020; 98: 233-234Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar; and Figure 3, p. 393 in Haguenau10Haguenau F. “Viruslike” particles as observed with the electron microscope.in: Dalton A.J. Haguenau F. Ultrastructure of Animal Viruses and Bacteriophages. Academic Press, Waltham, MA1973: 391-397Google Scholar). The article by Kissling et al.2Kissling 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 (225) Google Scholar is concerning, as electron microscopy is the only alleged evidence presented in support of the suggestion that coronaviruses are actually present in this kidney tissue; all other tests for coronavirus in kidney were negative. These micrographs do not support the statement that the particles are indeed viruses. Knowledge of virus morphology and morphogenesis, as well as of cellular architecture, is necessary to distinguish viral pathogens from normal subcellular organelles. This distinction is frequently difficult, because numerous cellular components can masquerade as viruses.7Miller S.E. Detection and identification of viruses by electron microscopy.J Electron Microsc Tech. 1986; 4: 265-301Crossref PubMed Scopus (46) Google Scholar, 8Miller S.E. Problems and pitfalls in diagnostic electron microscopy.Microsc Microanal. 2012; 18: 172-173Crossref Scopus (5) Google Scholar, 9Calomeni E. Satoskar A. Ayoub I. et al.Multivesicular bodies mimicking SARS-CoV-2 in patients without COVID-19.Kidney Int. 2020; 98: 233-234Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 10Haguenau F. “Viruslike” particles as observed with the electron microscope.in: Dalton A.J. Haguenau F. Ultrastructure of Animal Viruses and Bacteriophages. Academic Press, Waltham, MA1973: 391-397Google Scholar, 11Goldsmith C.S. Miller S.E. Martines R.B. et al.Electron microscopy of SARS-CoV-2: a challenging task.Lancet. 2020; 395: e99Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar We are grateful to Cynthia S. Goldsmith, Centers for Disease Control and Prevention, for critically reviewing this letter, providing helpful suggestions, and supplying the figure of severe acute respiratory syndrome coronavirus 2. We also thank Dr. David N. Howell for reviewing this manuscript. Collapsing glomerulopathy in a COVID-19 patientKidney InternationalVol. 98Issue 1PreviewThe first available reports indicate that renal involvement is relatively frequent in patients with novel coronavirus disease 2019 (COVID-19) due to the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Up to 43% of patients present with proteinuria (including 10% with heavy proteinuria), 11% with hematuria, and 3.5% to 5% with acute kidney injury.1,2 Both proteinuria and acute kidney injury are associated with increased mortality.1 However, the exact mechanisms underlying renal injury in patients with COVID-19 are unclear as renal pathology data are lacking. Full-Text PDF Open AccessMultivesicular bodies mimicking SARS-CoV-2 in patients without COVID-19Kidney InternationalVol. 98Issue 1PreviewIt is now well known that patients with novel coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) commonly have kidney complications, including acute kidney injury, proteinuria, and hematuria. Recent publications in Kidney International used electron microscopy (EM) to detect the virus in autopsy or biopsy specimens of the kidney.1,2 Most of the published images depicting the suspected virus are very similar, if not identical, to multivesicular bodies (MVBs). Full-Text PDF Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in ChinaKidney InternationalVol. 98Issue 1PreviewAlthough the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help define this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining. Patients were on average 69 years (19 male and 7 female) with respiratory failure associated with multiple organ dysfunction syndrome as the cause of death. Full-Text PDF Open AccessIn This IssueKidney InternationalVol. 98Issue 1PreviewThe kidney seems to be a target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Su and colleagues examined the kidneys of patients who died of coronavirus 2019 (COVID-19), and using electron microscopy (EM), found spherical structures in podocytes and the tubular epithelium that were felt to be coronavirus inclusions. In addition, tubules stained for SARS-CoV-2 nucleoprotein were positive. Similarly, Kissling and colleagues reported collapsing focal segmental glomerular sclerosis (FSGS) in a patient with COVID-19 who experienced a rapid decline in kidney function. Full-Text PDF The authors replyKidney InternationalVol. 98Issue 1PreviewWe thank Drs. Miller and Brealey1 for their comments and fully acknowledge their expertise in the field of electron microscopy. We also acknowledge our uncertainties regarding the exact nature of the particles seen in the podocytes in our patient’s kidney biopsy, and we were cautious in the interpretation of these findings. Following Drs. Miller and Brealey’s comments,1 we have modified our letter before its final publication in the journal to further underline that these particles may correspond to nonviral entities. Full-Text PDF The authors replyKidney InternationalVol. 98Issue 1PreviewWe have carefully read and considered the letter from Prof. Miller and Dr. Brealey,1 distinguished experts of electron microscopy (EM), and appreciate that they pointed out the limitations of our study.2 Full-Text PDF" @default.
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