The potential role of COVID-19 in the induction of DNA damage

Pánico, Pablo; Ostrosky‐Wegman, Patricia; Salazar, Ana Marı́a

doi:10.1016/j.mrrev.2022.108411

Cited by 29 publications

(20 citation statements)

References 91 publications

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“…A recent review suggested that SARS-CoV2 induces S-phase cell cycle arrest by promoting replication fork stress, possibly through its virus protein nsp13 which is known to interfere with DNA polymerase δ (POLD). 49 We do not know how POLD functions in Covid-19 patients based, but we do however observe an increase of POLD1 protein levels in PBMC and upregulation of POLD3 in regulatory T cells. However, cell cycle regulators do also have important immunomodulatory roles in, for example, interferon signaling and T cell activation.…”

Section: Discussioncontrasting

confidence: 57%

DNA Repair Mechanisms are Activated in Circulating Lymphocytes of Hospitalized Covid-19 Patients

Olsen¹,

Huse²,

Sousa³

et al. 2022

JIR

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Purpose Reactive oxygen species (ROS) are an important part of the inflammatory response during infection but can also promote DNA damage. Due to the sustained inflammation in severe Covid-19, we hypothesized that hospitalized Covid-19 patients would be characterized by increased levels of oxidative DNA damage and dysregulation of the DNA repair machinery. Patients and Methods Levels of the oxidative DNA lesion 8-oxoG and levels of base excision repair (BER) proteins were measured in peripheral blood mononuclear cells (PBMC) from patients (8-oxoG, n = 22; BER, n = 17) and healthy controls (n = 10) (Cohort 1). Gene expression related to DNA repair was investigated in two independent cohorts of hospitalized Covid-19 patients (Cohort 1; 15 patents and 5 controls, Cohort 2; 15 patients and 6 controls), and by publicly available datasets. Results Patients and healthy controls showed comparable amounts of oxidative DNA damage as assessed by 8-oxoG while levels of several BER proteins were increased in Covid-19 patients, indicating enhanced DNA repair in acute Covid-19 disease. Furthermore, gene expression analysis demonstrated regulation of genes involved in BER and double strand break repair (DSBR) in PBMC of Covid-19 patients and expression level of several DSBR genes correlated with the degree of respiratory failure. Finally, by re-analyzing publicly available data, we found that the pathway Hallmark DNA repair was significantly more regulated in circulating immune cells during Covid-19 compared to influenza virus infection, bacterial pneumonia or acute respiratory infection due to seasonal coronavirus. Conclusion Although beneficial by protecting against DNA damage, long-term activation of the DNA repair machinery could also contribute to persistent inflammation, potentially through mechanisms such as the induction of cellular senescence. However, further studies that also include measurements of additional markers of DNA damage are required to determine the role and precise molecular mechanisms for DNA repair in SARS-CoV-2 infection.

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Section: Discussioncontrasting

confidence: 57%

DNA Repair Mechanisms are Activated in Circulating Lymphocytes of Hospitalized Covid-19 Patients

Olsen¹,

Huse²,

Sousa³

et al. 2022

JIR

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“…DNA damage response and repair mechanisms have been involved in the pathogenesis of chronic conditions such as diabetes and cardiovascular disease [ 66 ]. However, the role of SARS‐CoV‐2 in inducing genome instability has not been fully ascertained.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic profiling of cardiac tissues from SARS‐CoV‐2 patients identifies DNA damage

et al. 2022

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The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is known to present with pulmonary and extra‐pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS‐CoV‐2 infection is likely to lead to more severe disease, with multi‐organ effects, including cardiovascular disease. SARS‐CoV‐2 has been associated with acute and long‐term cardiovascular disease, but the molecular changes that govern this remain unknown. In this study, we investigated the host transcriptome landscape of cardiac tissues collected at rapid autopsy from seven SARS‐CoV‐2, two pH1N1, and six control patients using targeted spatial transcriptomics approaches. Although SARS‐CoV‐2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1‐like macrophage infiltration in the cardiac tissues of COVID‐19 patients. The DNA damage present in the SARS‐CoV‐2 patient samples, were further confirmed by γ‐H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of interferon‐stimulated genes, in particular interferon and complement pathways, when compared with COVID‐19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS‐CoV‐2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra‐pulmonary organs, including the cardiovascular system of COVID‐19 patients, to delineate the immunopathobiology of SARS‐CoV‐2 infection, and long term impact on health.

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“…Studies have shown that in ammation and oxidative stress in viral infections have genotoxic effects [35]. Chronic in ammation increases the formation of reactive oxygen species [36].…”

Section: Discussionmentioning

confidence: 99%

The effect of inflammation and oxidative stress on DNA damage in COVID-19 patients

Tepebaşı

İlhan

Temal

et al. 2022

Preprint

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Background: COVID-19 disease, which spreads all over the world, is a disease characterized by widespread inflammation and affects many organs, especially the lungs. The resulting inflammation can lead to the generation of reactive oxygen radicals, leading to oxidative DNA damage.Methods and Results: Pneumonia severity of a total of 95 hospitalized patients with positive RT-PCR test was determined and divided into three groups mild, moderate, and severe/critical. Inflammation markers (Neutrophil-lymphocyte ratio, serum reactive protein, procalcitonin, etc.) were determined, and IL-10 and IF γ measurements were analyzed using the enzyme-linked immunosorbent assay method. In the evaluation of oxidative damage, total thiol, native thiol, disulfide, and IMA levels were determined by measuring spectrophotometrically. The percentage of tail DNA obtained by the comet assay method was used to determine oxidative DNA damage. As a result, when mild and severe/critical groups were compared, we found that total thiol, native thiol, and disulfide levels decreased significantly in the severe/critical group due to the increase in inflammation markers and cytokine levels (p <0.05). We could not detect any significance in IMA levels between the groups (p> 0.05). At the same time, we determined that there was an increase in the tail DNA percent level, that is, DNA damage, due to the increased oxidative effect.Conclusion: As a result, we found that increased inflammation and reactive oxygen species due to the increase in pneumonia increased in those with severe and severe pneumonia, which in turn damaged DNA. We think that it would be useful to follow up on the DNA damage in these patients in terms of neurodegenerative diseases and cancer development.

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The potential role of COVID-19 in the induction of DNA damage

Cited by 29 publications

References 91 publications

DNA Repair Mechanisms are Activated in Circulating Lymphocytes of Hospitalized Covid-19 Patients

DNA Repair Mechanisms are Activated in Circulating Lymphocytes of Hospitalized Covid-19 Patients

Transcriptomic profiling of cardiac tissues from SARS‐CoV‐2 patients identifies DNA damage

The effect of inflammation and oxidative stress on DNA damage in COVID-19 patients

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