"Highlights
- Increased DNA damage is observed in COVID-19 patients.
- The extent of DNA lesions correlates with disease severity.
- DNA breaks are induced by SARS-CoV-2 spike proteins.
- Co-morbidities and antiviral drugs also contribute to DNA damage...
Introduction
... Although there are limited studies on how SARS-CoV-2 infection affects certain molecular pathways, including oxidative stress and DNA damage, some have suggested that the virus causes damage to cellular DNA, as shown by the presence of micronuclei, DNA repair foci, and increased comet tails in infected cells...
Thus, the genotoxic effects of COVID-19 infection should be attentively monitored.
For the present review, PubMed database was used to search for keywords such as, 'COVID-19 and DNA damage', 'SARS-CoV-2 and DNA damage', and 'COVID-19 and comet assay'...
Possible mechanisms of DNA damage
... Lesiow et al. proposed a reasonable explanation for the DNA-damaging action of viral spikes. They demonstrated that two peptide fragments derived from the spike bind Cu[II] ions and form three‑nitrogen complexes, which trigger the overproduction of reactive oxygen species (ROS), breaking DNA strands. ROS overproduction is observed mainly in the mitochondria. The observed increase in free mitochondrial DNA in the serum of patients with COVID-19 likely develops following the above mechanism). When injected into mice, the spike protein triggers oxidative stress and double-stranded DNA breaks in the lung tissue of the animals. Similar effects were observed in human lung cell lines and explants, and the authors compared the spike-produced damage to the effects of ionising radiation. Spike protein S1, which binds to the angiotensin receptor, induces DNA breaks and premature senescence in cultured human endothelial cells. It exerts adverse effects on tumour cells by blocking p53 and other apoptosis-related factors, which decrease the sensitivity of cancer cells to chemotherapy...
Vaccination and therapy
DNA damage can affect the efficiency of vaccination against SARS-CoV-2; increased oxidative stress and the level of DNA double-strand breaks were observed in the nucleated blood cells of elderly patients, and both processes were further increased by vaccination... Treatment with COVID-19 can also have genotoxic effects. For example, chest radiography appears dangerous from this perspective. Antiviral drugs can also exert genotoxic effects [e.g., favipiravir, molnupiravir, hydroxychloroquine]...
Conclusions and perspectives
... SARS-CoV-2 proteins directly induce DNA damage. Indirect action via triggering oxidative stress or inhibition of DNA repair pathways also occurs, further weakening the resistance to infection and forming a vicious circle. The level of DNA damage correlates with the severity of the disease and influences sequelae during the post-COVID-19 period. Antiviral therapies enhance the genotoxic effects of infections per se. These factors may increase the risk of carcinogenesis and mutation."
© 2025 The Author(s). Published by Elsevier B.V.
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