The authors reply
Authors: Hua Su, Ding Gao, Hai-Chun Yang, Agnes B. Fogo, Xiu Nie, Chun Zhang
Journal: Kidney International (2020)

We have carefully read and considered the letter from Prof. Miller and Dr. Brealey,1Miller S.E. Brealey J.K. Visualization of putative coronavirus in kidney.Kidney Int. 2020; 98: 231-232Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar distinguished experts of electron microscopy (EM), and appreciate that they pointed out the limitations of our study.2Su 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 We agree with Miller and Brealey'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 severe acute respiratory syndrome (SARS) in China in 2003 and human monkey pox in the United States in 2003 were both first identified by EM. In addition, with our immunofluorescence staining for SARS-coronavirus (CoV) nuclear protein as we presented in our paper (Figure 3d)2Su 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 and the recent publications of ultrastructural feature of SARS-CoV-2,3Varga Z. Flammer A.J. 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,4Kissling 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 consider the structures as possible, but not definitively proven, CoV. We have therefore prudently changed the description in the preprint version of our article of "viral particle" to "coronavirus-like particle." Ideally, immuno-EM or in situ hybridization studies to assess local protein or RNA levels of CoV 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. Visualization of putative coronavirus in kidneyKidney InternationalVol. 98Issue 1PreviewWe 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. Su et al.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 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. Full-Text PDF 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 AccessRenal 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 Access