A recent study demonstrates that SARS-CoV-2, the virus responsible for COVID-19, has an impact on DNA integrity and elicits an altered DNA damage response. Specifically, two viral proteins (ORF6 and NSP13) cause degradation of the DNA damage response kinase CHK1, leading to a shortage of deoxynucleotide triphosphate (dNTP). This shortage impairs DNA replication and repair, leading to DNA damage, activation of pro-inflammatory pathways, and cellular senescence. The virus’ N-protein further interferes with damage-induced long non-coding RNAs, reducing DNA repair. These findings were observed in both infected mice and COVID-19 patients, indicating that SARS-CoV-2 poses a threat to genome integrity and induces altered DNA damage response, inflammation, and cellular senescence by manipulating cellular processes.