Electron microscopy of SARS-CoV-2: a challenging task

We read with interest the Correspondence by Zsuzsanna Varga and colleagues¹ on the possible infection of endothelial cells by SARS-CoV-2 using electron microscopic (EM) images as evidence. However, we believe the EM images in the Correspondence do not show coronavirus particles but instead show cross-sections of the rough endoplasmic reticulum (RER). These spherical structures are surrounded by dark dots, which might have been interpreted as spikes on coronavirus particles but are instead ribosomes. The purported particles are free within the cytoplasm, whereas within a coronavirus-infected cell, accumulations of virus particles would be found in membrane-bound areas in the cisternae of the RER–Golgi area, where the spikes would be located on the inside of the cisternal space.² In addition, cross-sections through the viral nucleocapsid are not seen in the interior of these structures as would be found with coronavirus particles (figure ).

Figure.

Viral isolate grown in cell culture

Spherical coronavirus particles with cross-sections through the nucleocapsid, seen as black dots, are clustered within a membrane which separates them from the cytoplasm.

Just recently, there have been two additional reports3, 4 in which structures that can normally be found in the cytoplasm of a cell have been misinterpreted as viral particles.⁵ EM can be a powerful tool to show evidence of infection by a virus, but care must be taken when interpreting cytoplasmic structures to correctly identify virus particles.