key: cord-0936953-kq2knqgb authors: Miller, Sara E.; Brealey, John K. title: Visualization of Putative Coronavirus in Kidney date: 2020-05-08 journal: Kidney Int DOI: 10.1016/j.kint.2020.05.004 sha: 65e1da9f5d57ea9f6c70285a43513b2fdd0415aa doc_id: 936953 cord_uid: kq2knqgb nan Dear Editors of Kidney International, We read with concern the articles that report the presence of coronavirus in kidney based on electron microscopic evidence (1, 2) . Neither article, in fact, demonstrates the presence of coronavirus in the kidney. The authors of one paper (1) 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 Figs a, b (~60 nm) are somewhat smaller than coronaviruses (~80 to140+ nm), but more importantly, their "spikes" (peplomers) are in contact with the cytosol, as are those on clathrin-coated vesicles; the larger particle in d also has spikes that are touching cytosol and does not have a dense core. Coronaviruses, on the other hand, have their projections either facing the extracellular space between cells or the space inside vacuoles within the cells (3, 4, 5) . This phenomenon is due to the fact that coronaviruses receive their outer covering by budding into or upon 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 (Fig 1) . These virions get out of the cell by exocytosis 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, since numerous cellular components can masquerade as viruses (7, 8, 9) . Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China Collapsing glomerulopathy in a COVID-19 patient Ultrastructural characterization of SARS coronavirus. Emerg Infect Dis An overview of their replication and pathogenesis Diagnosis of viral infection by electron microscopy Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections Ultrastructural Pathology of the Cell and Matrix. 4 th Ed Viruslike particles as observed with the electron microscope Detection and identification of viruses by electron microscopy Problems and pitfalls in diagnostic electron microscopy 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 SARS CoV-2. We also thank Dr. David Howell for reviewing this manuscript.Literature cited: