Study of a novel aspect of viral-host interaction upon SARS-CoV-2 infection using bulk RNA-seq

Prolonged SARS-CoV-2 RNA shedding and the recurrence of PCR-positive tests have been widely reported in patients after recovery; however, most of these patients were not infectious. We investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome and that transcription of the integrated sequences might account for some of the positive PCR tests. In support of this hypothesis, we found that DNA copies of SARS-CoV-2 sequences can be integrated into the human genome with target site duplications flanking the viral sequences and consensus LINE1 endonuclease recognition sequences at the integration sites, suggesting a LINE1 mediated, target-primed reverse transcription and retroposition mechanism. We also present evidence that suggests that a large fraction of the viral sequences found in some patient derived tissues were transcribed from integrated DNA copies of viral sequences. Our data provide a novel insight into the consequence of SARS-CoV-2 infections that may help to explain why patients can continue to produce viral RNA after recovery.