Difficulties in Differentiating Coronaviruses from Subcellular Structures in Human Tissues by Electron Microscopy
Hannah Bullock, Cynthia S. Goldsmith, Sherif R. Zaki, Roosecelis B. Martines, Sara Miller
Abstract
T he Coronaviridae family of viruses contains sev- eral human pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease (CO-VID-19) pandemic. Since early 2020, the unprecedented collective response to the COVID-19 pandemic from the scientifi c and medical community has led to numerous SARS-CoV-2-related publications and underscored the urgent need to demonstrate and verify the presence of coronavirus directly in tissues. Among these publications are reports describing the pathology of SARS-CoV-2 infection in patient specimens, which have been scrutinized intensely by electron microscopy (EM) for evidence of the virus. Consequently, several articles have erroneously described the identifi cation of coronavirus particles by EM in the lung (1-6), kidney ( data, https://doi.org/10.1101 /2020.03.04.20031120), heart (14,15), brain (16), liver (17), intestine (6,18), skin (19), and placenta (20-22) (Table ). However, most of the presumed virus or virus-like particles shown in all of these reports either represent normal subcellular organelles previously demonstrated in cells (23) or, otherwise, lack sufficient ultrastructure and morphologic features to be conclusively identifi ed as coronavirus. Since early May 2020, letters to the editors of several journals have refuted these descriptions (24-30), yet the misidentifi cation of coronavirus particles continues. It is essential for our collective understanding of CO-VID-19 clinical pathology and pathogenesis as well as the fi eld of diagnostic EM that these misidentifi cations of SARS-CoV-2 particles be addressed.