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Histopathology . Hunting coronavirus by transmission electron microscopy - a guide to SARS-CoV-2-associated ultrastructural pathology in COVID-19 t

tetano

Editor, Senior Moderator
Histopathology


. 2020 Sep 27.
doi: 10.1111/his.14264. Online ahead of print.
Hunting coronavirus by transmission electron microscopy - a guide to SARS-CoV-2-associated ultrastructural pathology in COVID-19 tissues


Helmut Hopfer[SUP] 1 [/SUP], Martin C Herzig[SUP] 1 [/SUP], Rainer Gosert[SUP] 2 [/SUP], Thomas Menter[SUP] 1 [/SUP], J?rgen Hench[SUP] 1 [/SUP], Alexandar Tzankov[SUP] 1 [/SUP], Hans H Hirsch[SUP] 2 3 4 [/SUP], Sara E Miller[SUP] 5 [/SUP]



Affiliations

Abstract

Transmission electron microscopy has become a valuable tool to investigate tissues of COVID-19 patients because it allows visualisation of SARS-CoV-2, but the "virus-like particles" described in several organs have been highly contested. Because most electron microscopists in pathology are not accustomed to analysing viral particles and subcellular structures, our review aims to discuss the ultrastructural changes associated with SARS-CoV-2 infection and COVID-19 with respect to pathology, virology, and electron microscopy. Using micrographs from infected cell cultures and autopsy tissues, we show how coronavirus replication affects ultrastructure and put the morphological findings in the context of viral replication, which induces extensive remodelling of the intracellular membrane systems. Virions assemble by budding into the endoplasmic reticulum-Golgi intermediate complex and are characterized by electron dense dots of cross-sections of the nucleocapsid inside the viral particles. Physiological mimickers such as multivesicular bodies or coated vesicles serve as perfect decoys. Compared to other in-situ techniques, transmission electron microscopy is the only method to visualize assembled virions in tissues and will be required to prove SARS-CoV-2 replication outside the respiratory tract. In practice, documenting in tissues the characteristic features seen in infected cell cultures, seems to be much more difficult than anticipated. In our view, the hunt for coronavirus by transmission electron microscopy is still on.

Keywords: coronavirus; electron microscopy; ultrastructure; virus replication.
 
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