Background
The novel coronavirus SARS-CoV-2 is the etiological agent of COVID-19. This virus has become one of the most dangerous in recent times with a very high rate of transmission. At present, several publications show the typical crown-shape of the novel coronavirus grown in cell cultures. However, an integral ultramicroscopy study done directly from clinical specimens has not been published.
Methods
Nasopharyngeal swabs were collected from two Cuban individuals, one asymptomatic and RT-PCR negative (negative control) and the other from a COVID-19 symptomatic and RT-PCR positive for SARS CoV-2. Samples were treated with an aldehyde solution and processed by Scanning Electron Microscopy, Confocal Microscopy and, Atomic Force Microscopy. Improvement and segmentation of coronavirus images were performed by mathematic algorithms.
Results
The images of the negative control sample showed the characteristic healthy microvilli morphology at the apical region of the nasal epithelial cells. As expected, they do not display virus-like structures. The images of the positive sample showed characteristic coronavirus-like particles and evident destruction of microvilli. In some regions, virions gemmating through the cell membrane were observed. Microvilli destruction could explain the anosmia reported by some patients. Virus-particles emerging from the cell-surface with a variable size ranging from 80 to 400 nm were observed by scanning electron microscopy (SEM). A confocal study showed viral antigen recognition in the apical cells zone.
Conclusions
The integral microscopy study showed that SARS-CoV-2 has a similar image to SARS-CoV. The application of several high-resolution microscopy techniques to clinical samples can help to answer important questions its replicative cycle and immunopathogenic mechanism of this novel coronavirus, relevant for the development of new treatments against this disease.

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Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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On 18 Jan, 2021
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On 14 Dec, 2020
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Received 12 Dec, 2020
Invitations sent on 06 Dec, 2020
On 29 Nov, 2020
On 29 Nov, 2020
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Posted 25 Nov, 2020
Received 25 Nov, 2020
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On 18 Nov, 2020
On 17 Nov, 2020
Invitations sent on 17 Nov, 2020
On 17 Nov, 2020
On 17 Nov, 2020
On 17 Nov, 2020
Posted 24 Jun, 2020
On 04 Aug, 2020
Received 02 Aug, 2020
On 27 Jul, 2020
Received 27 Jul, 2020
Received 27 Jul, 2020
On 24 Jul, 2020
On 23 Jul, 2020
On 23 Jul, 2020
On 23 Jul, 2020
Invitations sent on 23 Jul, 2020
On 29 Jun, 2020
On 29 Jun, 2020
On 23 Jun, 2020
On 17 Jun, 2020
On 18 Jan, 2021
On 17 Jan, 2021
On 17 Jan, 2021
On 17 Jan, 2021
On 14 Dec, 2020
On 12 Dec, 2020
Received 12 Dec, 2020
Invitations sent on 06 Dec, 2020
On 29 Nov, 2020
On 29 Nov, 2020
On 29 Nov, 2020
Posted 25 Nov, 2020
Received 25 Nov, 2020
Received 23 Nov, 2020
On 22 Nov, 2020
Received 21 Nov, 2020
On 18 Nov, 2020
On 17 Nov, 2020
Invitations sent on 17 Nov, 2020
On 17 Nov, 2020
On 17 Nov, 2020
On 17 Nov, 2020
Posted 24 Jun, 2020
On 04 Aug, 2020
Received 02 Aug, 2020
On 27 Jul, 2020
Received 27 Jul, 2020
Received 27 Jul, 2020
On 24 Jul, 2020
On 23 Jul, 2020
On 23 Jul, 2020
On 23 Jul, 2020
Invitations sent on 23 Jul, 2020
On 29 Jun, 2020
On 29 Jun, 2020
On 23 Jun, 2020
On 17 Jun, 2020
Background
The novel coronavirus SARS-CoV-2 is the etiological agent of COVID-19. This virus has become one of the most dangerous in recent times with a very high rate of transmission. At present, several publications show the typical crown-shape of the novel coronavirus grown in cell cultures. However, an integral ultramicroscopy study done directly from clinical specimens has not been published.
Methods
Nasopharyngeal swabs were collected from two Cuban individuals, one asymptomatic and RT-PCR negative (negative control) and the other from a COVID-19 symptomatic and RT-PCR positive for SARS CoV-2. Samples were treated with an aldehyde solution and processed by Scanning Electron Microscopy, Confocal Microscopy and, Atomic Force Microscopy. Improvement and segmentation of coronavirus images were performed by mathematic algorithms.
Results
The images of the negative control sample showed the characteristic healthy microvilli morphology at the apical region of the nasal epithelial cells. As expected, they do not display virus-like structures. The images of the positive sample showed characteristic coronavirus-like particles and evident destruction of microvilli. In some regions, virions gemmating through the cell membrane were observed. Microvilli destruction could explain the anosmia reported by some patients. Virus-particles emerging from the cell-surface with a variable size ranging from 80 to 400 nm were observed by scanning electron microscopy (SEM). A confocal study showed viral antigen recognition in the apical cells zone.
Conclusions
The integral microscopy study showed that SARS-CoV-2 has a similar image to SARS-CoV. The application of several high-resolution microscopy techniques to clinical samples can help to answer important questions its replicative cycle and immunopathogenic mechanism of this novel coronavirus, relevant for the development of new treatments against this disease.

Figure 1

Figure 2

Figure 3

Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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