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

Goldsmith, Cynthia S.; Miller, Sara; Martines, Roosecelis B; Bullock, Hannah; Zaki, Sherif R.

doi:10.1016/s0140-6736(20)31188-0

Cited by 172 publications

(184 citation statements)

References 5 publications

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“…Goldsmith et al pointed out that images published as putative virions within endothelial cells actually represented normal cellular structures such as endoplasmic reticulum rather than virus. 54 As in our study, Shieh et al described positive IHC for H1N1 influenza in endothelium only in rare cases. 50 Furthermore, although we did observe thrombi, microthrombi and focal vascular inflammation (Supporting information, Discussion and Supporting information, Figure S2) we did not observe lesions of thrombotic necrotising capillary injury, endothelial cell necrosis or endothelialitis as reported by others.…”

Section: Discussionsupporting

confidence: 74%

Insights into pathogenesis of fatal COVID‐19 pneumonia from histopathology with immunohistochemical and viral RNA studies

et al. 2020

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IntroductionWe describe post‐mortem pulmonary histopathologic findings of COVID‐19 pneumonia in patients with a spectrum of disease course, from rapid demise to prolonged hospitalisation.Methods and resultsHistopathologic findings in post‐mortem lung tissue from eight patients who died from COVID‐19 pneumonia were reviewed. Immunohistochemistry (IHC) and next‐generation sequencing (NGS) were performed to detect virus. Diffuse alveolar damage (DAD) was seen in all cases with a spectrum of acute phase and/or organising phase. IHC with monoclonal antibodies against SARS‐CoV‐2 viral nucleoprotein and spike protein detected virus in areas of acute but not organising DAD, with intracellular viral antigen and RNA expression seen predominantly in patients with duration of illness less than 10 days. Major vascular findings included thrombi in medium‐ and large‐calibre vessels, platelet microthrombi detected by CD61 IHC and fibrin microthrombi.ConclusionsPresence of SARS‐CoV‐2 viral RNA by NGS early in the disease course and expression of viral antigen by IHC exclusively in the acute, but not in the organising phase of DAD, suggests that the virus may play a major role in initiating the acute lung injury of DAD, but when DAD progresses to the organising phase the virus may have been cleared from the lung by the patient's immune response. These findings suggest the possibility of a major change during the disease course of COVID‐19 pneumonia that may have therapeutic implications. Frequent thrombi and microthrombi may also present potential targets for therapeutic intervention.

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Section: Discussionsupporting

confidence: 74%

Insights into pathogenesis of fatal COVID‐19 pneumonia from histopathology with immunohistochemical and viral RNA studies

et al. 2020

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“…This observation, together with the frequent findings of vascular damage, has focused the research of the virus in vascular tissues. Some authors reported the presence of putative SARS-CoV-2 particles in the cytoplasm of endothelial cells [35,40] but these observations have been questioned by experts [64]. TEM can be a powerful tool to find evidence of infection by a virus, but care must be taken when interpreting unequivocally such cytoplasmic structures as viral particles.…”

Section: Electron Microscopymentioning

confidence: 99%

Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists

et al. 2020

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Since its initial recognition in December 2019, Coronavirus disease 19 (COVID-19) has quickly spread to a pandemic infectious disease. The causative agent has been recognized as a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affecting the respiratory tract. To date, no vaccines are available nor any specific treatment. To limit the number of infections, strict directives have been issued by governments that have been translated into equally rigorous guidelines notably for post-mortem examinations by international and national scientific societies. The recommendations for biosafety control required during specimen collection and handling have strongly limited the practice of autopsies of the COVID-19 patients to a few adequate laboratories. A full pathological examination has always been considered an important tool to better understand the pathophysiology of diseases, especially when the knowledge of an emerging disorder is limited and the impact on the healthcare system is significant. The first evidence of diffuse alveolar damage in the context of an acute respiratory distress syndrome has now been joined by the latest findings that report a more complex scenario in COVID-19, including a vascular involvement and a wide spectrum of associated pathologies. Ancillary tools such as electron microscopy and molecular biology used on autoptic tissue samples from autopsy are also significantly contributing to confirm and/or identify new aspects useful for a deeper knowledge of the pathogenetic mechanisms. This article will review and summarize the pathological findings described in COVID-19 until now, chiefly focusing on the respiratory tract, highlighting the importance of autopsy towards a better knowledge of this disease.

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“…8,16,17 However, the identification of viral particles by electron microscropy is challenging, as they may easily be mistaken for normal cell organelles such as the endoplasmic reticulum (ER), clathrin-coated vesicles, or multivesicular bodies. [18][19][20] Overall, several arguments suggest that the PT may be a specific target for SARS-CoV-2 infection. Here, we analyzed the characteristics, extent, and structural correlates of PT dysfunction in a cohort of patients admitted with SARS-CoV-2 infection in a large academic hospital in Brussels, Belgium.…”

mentioning

confidence: 99%