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1/ A quick review of this preprint, since it is potentially very important for the pandemic and the novel mRNA vaccines and since it relates to my expertise. In my mind, the conclusions made by authors is not supported by the presented data. https://www.biorxiv.org/content/10.1101/2020.12.12.422516v1
2/ The analysis of human-CoV2 hybrid reads (fig1) is very preliminary and lacks key control analyses and experiments. Most important: are the predicted integrations random (as would be expected) or enriched for exons (artifacts)?
3/ Validation with alternative techniques (for example RT-PCR and northerns) would be essential as well as to validate a few integrations on the genomic level. The most likely explanation for these observations is that they are technical artefacts.
4/ The artificial transposition experiment (fig2) is pretty meaningless since it is artificial… this experiment also lacks a couple of key controls (LINE1-RT mutant). In my mind, this figure is a very weak data point. Does not prove SARS-CoV2 transposition in human cells.
5/ The expression analysis of L1s (fig3) actually proves the opposite of what the authors claim. The more detailed analysis in figS4 convincingly demonstrates that only evolutionary old L1s that lack a functional RT is transcriptionally induced, while young L1s remain silent.
6/ In summary, this manuscript provides no evidence that SARS-CoV2 can be retrotransposed into the human genome. The timing and quality of this release is worrying since this manuscript comes from outstanding labs and scientists.
