key: cord-0971984-c77x3btm
authors: Smith, Kelly D.; Akilesh, Shreeram; Alpers, Charles E.; Nicosia, Roberto F.
title: Am I a Coronavirus?
date: 2020-06-04
journal: Kidney Int
DOI: 10.1016/j.kint.2020.05.021
sha: 2db87f0243119e9245bdcf4a4a6ef790a73bcfca
doc_id: 971984
cord_uid: c77x3btm

nan

To the Editors, The paper by Su et al. analyzes renal pathologic findings in the kidneys of 26 patients that underwent post-mortem exam to understand the anatomic basis of kidney disease in the setting of fatal COVID-19 1 . The authors report the finding of viral particles in the kidney of COVID-19 patients and speculate that direct infection of the kidney by SARS-CoV-2 virus causes kidney disease.

Several findings within the manuscript by Su et al. are presented as definite evidence of specific disease processes without considering alternative explanations. For example, acute tubular injury (ATI) is reported in all cases, including patients with normal renal function. Discerning ATI from postmortem changes is notoriously problematic since autolysis can mimic and mask ATI 2 . Infiltration of inflammatory cells in an arcuate artery is highlighted in a micrograph in which characteristic features of muscular arteries, such as elastic lamina or defined muscular layers, are not apparent (Fig. 1d of Su et al. manuscript, ref. 1 ). Distension of small blood vessels by red blood cells is referred to as obstruction, when it may simply represent congestion. Isolated fibrin clots are interpreted as evidence of severe endothelial injury but could also be due to coagulopathy. Most importantly, small vesicular structures identified by electron microscopy (EM) are described as viral particles without consideration of other interpretations (Table 1) To support their interpretation of the electron micrographs, Su et al. present immunofluorescence studies performed on sections of formalin-fixed and paraffin embedded (FFPE) tissue. The distribution and quality of the positive anti-nucleocapsid protein staining bares striking resemblance to lipofuscin autofluorescence 6 . Controls were reported to stain as expected, but no images of the controls are provided, nor is there an explanation of what was used as positive and negative controls to validate this antibody for FFPE.

Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China

Renal pathologic spectrum in an autopsy series of patients with plasma cell dyscrasia

The intracellular sites of early replication and budding of SARS-coronavirus

Ultrastructure of human nasal epithelium during an episode of coronavirus infection

Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS)

Autofluorescence spectroscopy and imaging: a tool for biomedical research and diagnosis

Therefore, in our judgement, Su et al's findings of small vesicular structures that are not conclusively distinguished from cellular vesicles and immunostaining that resembles lipofuscin autofluorescence without adequate controls are not sufficient to establish definitive infection of renal tubular epithelial cells and podocytes by the SARS-CoV-2. More rigorous and definitive studies are required to answer this question. SARS-CoV-2 may in fact infect the kidney and contribute to kidney disease in COVID-19 patients, but this remains an open question in search of an answer.