Controversial pre-publication results suggest SARS-CoV-2 RNAs may be reverse transcribed in human cells by reverse transcriptase (RT) from LINE-1 elements, integrated into the cell genome, and subsequently transcribed. Furthermore, the authors argue that endogenous LINE-1 expression can be induced upon SARS-CoV-2 infection or by cytokine exposure, suggesting a possible molecular mechanism for SARS-CoV-2 retro-integration in patients with Cov-2. These somewhat frightening preprint observations suggest potential long-term impacts from some Cov-2 infections (https://doi.org/10.1101/2020.12.12.422516). Are the authors doing a public service by releasing this preprint or might this negatively impact some public behavior on the vaccines?

However, now that these ideas are presented, they raise key questions as to how to efficiently test and assess integration and to adequately consider its potential long-term risk that would seem to merit wide spread scientific attention. How might we determine their clinical relevance and see if CoV-2 is rare or sufficiently frequent in infected individuals to be a public health concern? Are there efficient ways to refute or support the proposed integration and its mechanism? Would Southern blot experiments or genomic DNA sequencing with the integration site on multiple recovered patients be helpful and convincing?

In general, what types of experimental tests, data, and analyses are needed to convincingly test the ideas in this preprint and to determine whether or not SARS-CoV-2 is reverse-transcribed and integrated in the human genome. If this is occurring, then how can we best assess the frequency, and if there a resultant potential for chronic illness?