Caution in Identifying Coronaviruses by Electron Microscopy

Miller, Sarah E.; Goldsmith, Cynthia S.

doi:10.1681/asn.2020050755

Cited by 55 publications

(41 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The ILVs found within a larger vesicles ( Figure 1 E) and Ref. 18 , 19 , 32 have been confused with SARS-CoV-2 particles 8 . Microvilli captured in plasma membrane invaginations can also mimic MVBs and be confused for viral particles ( Figure 1 F).…”

Section: Cellular Structures Mistaken For Virusmentioning

confidence: 98%

“…If prior knowledge is lacking or incomplete, the structure of the viral particles should be established with an appropriate model system, such as electron microscopy of in vitro infected cells. For coronavirus, Goldsmith and colleagues note that coronavirus spikes are often difficult to visualize in thin sections using transmission electron microscopy (TEM) 19 , and usually less obvious than clathrin coats. In addition, the nucleocapsid within the membrane of the viral particle has characteristic dot-like electron densities that are typically absent from cellular vesicles (Ref 19 and Figure 2 ).…”

Section: Proposed Criteria For Identification Of Viral Infection Of Tmentioning

confidence: 99%

“…For coronavirus, Goldsmith and colleagues note that coronavirus spikes are often difficult to visualize in thin sections using transmission electron microscopy (TEM) 19 , and usually less obvious than clathrin coats. In addition, the nucleocapsid within the membrane of the viral particle has characteristic dot-like electron densities that are typically absent from cellular vesicles (Ref 19 and Figure 2 ). The reported diameter of the virus is approximately 80 nm 35 .…”

Section: Proposed Criteria For Identification Of Viral Infection Of Tmentioning

confidence: 99%

“…Unfortunately, many of these studies are fraught with confusion over differentiating virus from normal structures within cells, and hence there has been an explosion of misinformation. Indeed, published manuscripts claiming to provide direct evidence of SARS-CoV-2 virus infecting in kidney cells and endothelial cells have provoked letters to the editor challenging these claims [15] , [16] , [17] , [18] , [19] , [20] . In this perspective we will discuss what is known about coronavirus infection and some of the basic ultrastructural cell biology that has been confused for coronavirus infection of cells, namely the machinery that controls endocytosis and exocytosis, and membrane transport within cells 21 .…”

mentioning

confidence: 99%

See 3 more Smart Citations

Characterizing Viral Infection by Electron Microscopy

Akilesh

Nicosia

Alpers

et al. 2021

The American Journal of Pathology

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Section: Cellular Structures Mistaken For Virusmentioning

confidence: 98%

Section: Proposed Criteria For Identification Of Viral Infection Of Tmentioning

confidence: 99%

Section: Proposed Criteria For Identification Of Viral Infection Of Tmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Characterizing Viral Infection by Electron Microscopy

Akilesh

Nicosia

Alpers

et al. 2021

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…One should keep in mind though that the diagnosis of coronavirus particles by electron microscopy is challenging due to the numerous similarly appearing normal cellular structures (e.g., clathrin‐coated vesicles, which are normal cell organelles involved in intracellular transport or cross‐sections of the rough endoplasmic reticulum), creating significant controversy (see e.g., (Miller & Brealey, 2020; Miller & Goldsmith, 2020; Su, Gao, et al, 2020; Su, Yang, et al, 2020) and (Goldsmith et al., 2020; Varga et al., 2020a, 2020b)). In fact, it was pointed out that “there are inherent difficulties in discrimination of cellular vesicles from viral particles solely by morphological evidence” (Su, Gao, et al, 2020).…”

Section: Neurological Manifestations In Covid‐19 Patientsmentioning

confidence: 99%

Severe acute respiratory syndrome coronavirus 2 infection reaches the human nervous system: How?

Uversky

Elrashdy

Aljadawi

et al. 2020

J of Neuroscience Research

View full text Add to dashboard Cite

Without protective and/or therapeutic agents the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection known as coronavirus disease 2019 is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS‐CoV‐2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS‐CoV‐2 components could use to reach the CNS and PNS, utilizing the within‐body cross talk between organs. The majority of SARS‐CoV‐2–infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune‐mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood–endothelial barrier may be considered as the main route for SARS‐CoV‐2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.

show abstract

A series of COVID‐19 autopsies with clinical and pathologic comparisons to both seasonal and pandemic influenza

McMullen

Pytel

Snyder

et al. 2021

The Journal of Pathology CR

View full text Add to dashboard Cite

Autopsies of patients who have died from COVID‐19 have been crucial in delineating patterns of injury associated with SARS‐CoV‐2 infection. Despite their utility, comprehensive autopsy studies are somewhat lacking relative to the global burden of disease, and very few comprehensive studies contextualize the findings to other fatal viral infections. We developed a novel autopsy protocol in order to perform postmortem examinations on victims of COVID‐19 and herein describe detailed clinical information, gross findings, and histologic features observed in the first 16 complete COVID‐19 autopsies. We also critically evaluated the role of ancillary studies used to establish a diagnosis of COVID‐19 at autopsy, including immunohistochemistry (IHC), in situ hybridization (ISH), and electron microscopy (EM). IHC and ISH targeting SARS‐CoV‐2 were comparable in terms of the location and number of infected cells in lung tissue; however, nonspecific staining of bacteria was seen occasionally with IHC. EM was unrevealing in blindly sampled tissues. We then compared the clinical and histologic features present in this series to six archival cases of fatal seasonal influenza and six archival cases of pandemic influenza from the fourth wave of the ‘Spanish Flu’ in the winter of 1920. In addition to routine histology, the inflammatory infiltrates in the lungs of COVID‐19 and seasonal influenza victims were compared using quantitative IHC. Our results demonstrate that the clinical and histologic features of COVID‐19 are similar to those seen in fatal cases of influenza, and the two diseases tend to overlap histologically. There was no significant difference in the composition of the inflammatory infiltrate in COVID‐19 and influenza at sites of acute lung injury at the time of autopsy. Our study underscores the relatively nonspecific clinical features and pathologic changes shared between severe cases of COVID‐19 and influenza, while also providing important caveats to ancillary methods of viral detection.

show abstract

Caution in Identifying Coronaviruses by Electron Microscopy

Cited by 55 publications

References 16 publications

Characterizing Viral Infection by Electron Microscopy

Characterizing Viral Infection by Electron Microscopy

Severe acute respiratory syndrome coronavirus 2 infection reaches the human nervous system: How?

A series of COVID‐19 autopsies with clinical and pathologic comparisons to both seasonal and pandemic influenza

Contact Info

Product

Resources

About