SARS-CoV-2 spreads through cell-to-cell transmission
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Abstract
It is currently unknown if SARS-CoV-2 can spread through cell–cell contacts, and if so, the underlying mechanisms and implications. In this work, we show, by using lentiviral pseudotyped virus, that the spike protein of SARS-CoV-2 mediates the viral cell-to-cell transmission, with an efficiency higher than that of SARS-CoV. We also find that cell–cell fusion contributes to cell-to-cell transmission, yet ACE2 is not absolutely required. While the authentic variants of concern (VOCs) B.1.1.7 (alpha) and B.1.351 (beta) differ in cell-free infectivity from wild type and from each other, these VOCs have similar cell-to-cell transmission capability and exhibit differential sensitivity to neutralization by vaccinee sera. Results from our study will contribute to a better understanding of SARS-CoV-2 spread and pathogenesis.
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SciScore for 10.1101/2021.06.01.446579: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of the Study: While in this work, we obtained evidence that SARS-CoV-2 spike more efficiently mediates cell-to-cell transmission than the SARS-CoV spike, a direct comparison using authentic viruses of both, especially in primary human lung and …
SciScore for 10.1101/2021.06.01.446579: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of the Study: While in this work, we obtained evidence that SARS-CoV-2 spike more efficiently mediates cell-to-cell transmission than the SARS-CoV spike, a direct comparison using authentic viruses of both, especially in primary human lung and airway epithelial cells, is needed. As an initial step toward this goal, we have attempted to apply rVSV-GFP-SARS-CoV-2 and rVSV-GFP-SARS-CoV to human primary bronchial and nasal epithelial cell cultures, but the efficiency of spread for both viruses was too low to draw any conclusion. Although in this work, we examined roles of ACE2 and endosomal proteases in cell-to-cell transmission vs. cell-free infection, how other host cofactors, including TMPRSS2, modulate this process will need to be investigated. Ultimately, we must determine the role, if any, of cell-to-cell transmission of SARS-CoV-2 in disease progression and pathogenesis in COVID-19 patients.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 60. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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