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. 2021 Jan 1;184(1):186. doi: 10.1111/bjd.19572

SARS‐CoV‐2 has not been detected directly by electron microscopy in the endothelium of chilblain lesions

JK Brealey 1, SE Miller 2,
PMCID: PMC9214016  PMID: 33000462

Abstract

Linked Article: Colmenero et al. Br J Dermatol 2020; 183:729–737.


Dear Editor, We are concerned that yet another erroneous report of the electron microscopic observation of coronavirus in tissue has been published. The paper by Colmenero et al. presents a study of skin biopsies from paediatric patients presenting with chilblains during the coronavirus disease 2019 (COVID‐19) pandemic.1 Seven cases were examined by histopathological and immunohistochemical techniques, and one of these was additionally studied by transmission electron microscopy. As part of the investigation, the authors report the electron microscopic visualization of coronaviruses in endothelial cells and apply this observation as supporting evidence that the vascular lesions arising in the chilblains are a manifestation of endothelial infection by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2).

The paper presents a representative electron micrograph depicting a round membrane‐bound structure measuring approximately 90 nm in diameter that is interpreted as a coronavirus based on its size and the presence of external projections. However, this is incorrect; the particle depicted is a clathrin‐coated vesicle – a normal subcellular organelle.2 While its size is consistent with that of a coronavirus, its morphology is not characteristic of this virus.35 For example, the structure is shown in direct contact with the cytosol and not within a membrane‐bound vacuole, as is observed for intracellular coronaviruses. Moreover, it lacks the characteristic speckled core that represents cross‐sections of the coiled coronavirus nucleocapsids. Also, while it is studded by electron‐dense material, producing a somewhat coronavirus‐like appearance at its margin, the appearance is typical of several normal intracellular constituents, including clathrin‐coated vesicles and circular profiles of rough endoplasmic reticulum.

Thus, the micrograph presented in this paper depicts a normal subcellular structure and not a coronavirus. Therefore, the conclusion that these structures ‘support a causal relation of the lesions with SARS‐CoV‐2’ cannot be supported by the electron microscopic data presented.

Author Contribution

John K Brealey: Conceptualization (equal); Investigation (equal); Resources (equal); Writing‐original draft (equal); Writing‐review & editing (equal). Sara E Miller: Conceptualization (equal); Investigation (equal); Resources (equal); Writing‐original draft (equal); Writing‐review & editing (equal).

Contributor Information

J.K. Brealey, Electron Microscopy Unit, Anatomical Pathology SA Pathology Adelaide SA Australia

S.E. Miller, Department of Pathology Duke University Medical Center Durham NC USA.

References

  1. Colmenero  I, Santonja  C, Alonso‐Riaño  M  et al. SARS‐CoV‐2 endothelial infection causes COVID‐19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases. Br J Dermatol  2020; 183:729–37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Roufosse  C, Curtis  E, Moran  L  et al. Electron microscopic investigations in COVID‐19: not all crowns are coronas. Kidney Int  2020; 98:505–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Goldsmith  CS, Miller  SE, Martines  RB  et al. Electron microscopy of SARS‐CoV‐2: a challenging task. Lancet  2020; 395:e99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Miller  SE, Brealey  JK. Visualization of putative coronavirus in kidney. Kidney Int  2020; 98:231–2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Miller  SE, Goldsmith  CS. Caution in identifying coronaviruses by electron microscopy. J Am Soc Nephrol  2020; 31:2223–4. [DOI] [PMC free article] [PubMed] [Google Scholar]

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