The authors reply

We 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

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)² and the recent publications of ultrastructural feature of SARS-CoV-2,^{3 , 4} 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.