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Authors: Guang Li et al. Link to paper: https://doi.org/10.1101/2020.04.11.037473

Journal/ Pre-Print: bioRxiv

Key Words: 3D histology, tissue clearing, lung, covid-19 patient

Research Highlights 

1. 3D histology on autopsied COVID-19 lung after tissue clearing

2. Extensive fibrin clotting in small capillaries within alveoli in this sample giving a potential illustration of pulmonary microangiopathy in 3D

3. Methodological advance on traditional histological techniques

Summary 

This study tests the potential benefit of new 3D histology processing to visualise lung tissue from a single COVID-19 positive patient. Following tissue clearance, virtual fluorescent H&E staining and optical sectioning light sheet imaging, good resolution 3D images were generated of the lung, representing a volume of up to 0.832 teravoxels. An extensive fibrin clotting was found in small capillaries within alveoli and corroborates with previous 2D histological studies.

While this study doesn’t add to our understanding and current knowledge of COVID19, it shows that new 3D histology methods can be adopted in the study of COVID-19 and may offer extra insight into its pathogenesis allowing the visualisation of bigger tissue volumes with less artefacts created.

Impact for SARS-CoV2/COVID19 research efforts

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19

Using new histological techniques allow 3-dimensional imaging of the patient samples that avoid the artefacts generated during tissue sectioning and 3D-reconstruction in classical 2D histology. 3D imaging leads to a better visualisation and of the histopathology of COVID-19 lung samples.

Study Type

· Patient Case study (lung autopsy of 1 COVID19 patient)

· Histology with optical clearance of human sample and diSPIM (Lightsheet) imaging

Strengths and limitations of the paper

Novelty: This study use recently developed techniques to performed 3D imaging on autopsied lung samples from a COVID-19 victim. The images provided are of high quality and corroborate the observations made by previous reports. The use of 3D imaging avoids physical sectioning of the samples needed for the classical histology techniques and decreases artefacts.

Standing in the field: The images provided are in agreement with some previous reports.

Appropriate statistics: There is no statistics. The data provided are anecdotal from 1 COVID-19 case without comparison to normal tissue.

Viral model used: COVID-19 patient

Translatability: There is no translational potential.

Main limitations:

- There are no new observations in this study regarding COVID-19.

- There is only lung sample of 1 COVID-19 victim and not even a control to compare it to.

- This study doesn’t convey that this 3D imaging techniques brought more information than the classical 2D imaging, on contrary, they point out features already observed in previous 2D studies.

- The instrument used in this study is expensive and may not be available in most hospital settings.

- The infrastructure for handling the massive data generated even for a single patient may not be available in most hospital settings.