key: cord-0011582-15a2avvk authors: Su, Hua; Gao, Ding; Yang, Hai-Chun; Fogo, Agnes B.; Nie, Xiu; Zhang, Chun title: Response to “Visualization of Putative Coronavirus in Kidney” date: 2020-05-16 journal: Kidney Int DOI: 10.1016/j.kint.2020.05.007 sha: 68b8d9178ee08a7672f4131aa1ce3cd3c02ab49a doc_id: 11582 cord_uid: 15a2avvk nan Dear Editors, We have carefully read and considered the letter from Prof. Sara E. Miller [1] , a distinguished expert of electron microscopy (EM), and appreciate her pointing out the limitations of our study [2] . We agree with Prof. Miller's point and recognize that there are inherent difficulties in discrimination of cellular vesicles from viral particles solely by morphological evidence, especially in routine EM processing of autopsy tissues. These conditions differ markedly from the in vitro negative staining of body fluids or cell culture which are the techniques usually utilized for optimal visualization of viral structure. However, EM is still an essential tool and a front-line evaluation method in the search for unknown pathogens in outbreaks or epidemics. For example, the causative agents of the outbreak of SARS in China at 2003 and human monkey pox in USA 2003 were both first identified by EM. In addition, with our immunofluorescence staining for SARS-CoV nuclear protein as we presented in our paper (Figure 3d ) and the recent publications of ultrastructural feature of SARS-CoV-2 [3, 4] , we consider the structures as possible, but not definitively proven, coronavirus. We have therefore prudently changed the description in the preprint version of our paper of "viral particle" to "coronavirus-like particle". Ideally, immunoelectron microscopy or in situ hybridization studies to assess local protein or RNA levels of the coronavirus will further clarify the possibility of direct kidney parenchymal infection. Such a combination of ultrastructural images and molecular data could then definitively identify viral-like particles as SARS-CoV-2 virus. Miller's Letter to the Editors Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China Endothelial cell infection and endotheliitis in COVID-19 Collapsing glomerulopathy in a COVID-19 patient