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DNA damage in peripheral blood lymphocytes of severely ill COVID-19 patients in relation to inflammatory markers and parameters of hemostasis

Mihaljevic et al., Mutagenesis, doi:10.1093/mutage/geac011, May 2022
https://c19early.org/mihaljevic.html
Observational study of 24 severely ill hospitalized COVID-19 patients showing significantly higher DNA damage in peripheral blood lymphocytes compared to 15 healthy controls. Favipiravir was associated with increased DNA damage.
Potential risks of favipiravir include kidney injury1-3, liver injury2-4, and mutagenicity, carcinogenicity, teratogenicity, embryotoxicity, and the creation of dangerous variants5-11.
Mihaljevic et al., 1 May 2022, Serbia, peer-reviewed, mean age 55.8, 8 authors. Contact: vrndic07@yahoo.com.
DNA damage in peripheral blood lymphocytes of severely ill COVID-19 patients in relation to inflammatory markers and parameters of hemostasis
Olgica Mihaljevic, Snezana Zivancevic-Simonovic, Vojislav Cupurdija, Milos Marinkovic, Jovana Tubic Vukajlovic, Aleksandra Markovic, Marijana Stanojevic-Pirkovic, Olivera Milosevic-Djordjevic
Mutagenesis, doi:10.1093/mutage/geac011
Bearing in the mind that a variety of agents can contribute to genome instability, including viral infections, the aim of this study was to analyze DNA damage in hospitalized COVID-19 patients and its relationship with certain laboratory parameters. The potential impact of applied therapy and chest X-rays on DNA damage was also estimated. The study population included 24 severely COVID-19 patients and 15 healthy control subjects. The level of DNA damage was measured as genetic damage index (GDI) by comet assay. The standard laboratory methods and certified enzymatic reagents for the appropriate autoanalyzers were performed for the determination of the biochemical and hematological parameters. COVID-19 patients had significantly higher level of DNA damage compared with control subjects. The absolute number of neutrophil leukocytes was statistically higher, while the absolute number of lymphocytes was statistically lower in COVID-19 patients than in healthy controls. The analysis of the relationship between DNA damage and laboratory parameters indicated that GDI was positively correlated with interleukin 6 (IL-6) concentration and negatively with platelet count in COVID-19 patients. The level of DNA damage was slightly higher in female patients, in whom it was demonstrated a positive correlation of GDI with C-reactive protein (CRP) and procalcitonin. Likewise, there was a negative relationship of GDI and platelet count, and positive relationship of GDI and activated partial thromboplastin time (aPTT) in female population. The applied therapy (antibiotics, corticosteroid, anticoagulant, and antiviral therapy) as well as chest X rays has been shown to have genotoxic potential. The level of DNA damage significantly corresponds to the inflammatory markers and parameters of hemostasis in COVID-19 patients. In conclusion, inflammation, smoking habit, applied therapy, and chest X rays contribute to a higher level of DNA damage in COVID-19 patients.
209 LDH, AST, ALT, CK, pro-BNP, urea, and creatinine. This is in line with the results of previous studies that dealt with the diagnostic and prognostic value of laboratory findings in COVID-19 patients [8, 47, 48] . The aggrevated inflammatory response in SARS-CoV-2 infection causes multiorgan dysfunction that is reflected through a remarkable increase in different laboratory parameters. However, the mentioned parameters did not show a significant relationship with DNA damage, nor the hemostasis parameters. Namely, we found that lower values of platelet count, as well as the higher values of aPTT correspond to a more pronounced DNA damage in females. It is assumed that hemostasis abnormalities in Conflict of Interest Statement None declared.
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DOI record: { "DOI": "10.1093/mutage/geac011", "ISSN": [ "0267-8357", "1464-3804" ], "URL": "http://dx.doi.org/10.1093/mutage/geac011", "abstract": "<jats:title>Abstract</jats:title>\n <jats:p>Bearing in the mind that a variety of agents can contribute to genome instability, including viral infections, the aim of this study was to analyze DNA damage in hospitalized COVID-19 patients and its relationship with certain laboratory parameters. The potential impact of applied therapy and chest X-rays on DNA damage was also estimated. The study population included 24 severely COVID-19 patients and 15 healthy control subjects. The level of DNA damage was measured as genetic damage index (GDI) by comet assay. The standard laboratory methods and certified enzymatic reagents for the appropriate autoanalyzers were performed for the determination of the biochemical and hematological parameters. COVID-19 patients had significantly higher level of DNA damage compared with control subjects. The absolute number of neutrophil leukocytes was statistically higher, while the absolute number of lymphocytes was statistically lower in COVID-19 patients than in healthy controls. The analysis of the relationship between DNA damage and laboratory parameters indicated that GDI was positively correlated with interleukin 6 (IL-6) concentration and negatively with platelet count in COVID-19 patients. The level of DNA damage was slightly higher in female patients, in whom it was demonstrated a positive correlation of GDI with C-reactive protein (CRP) and procalcitonin. Likewise, there was a negative relationship of GDI and platelet count, and positive relationship of GDI and activated partial thromboplastin time (aPTT) in female population. The applied therapy (antibiotics, corticosteroid, anticoagulant, and antiviral therapy) as well as chest X rays has been shown to have genotoxic potential. The level of DNA damage significantly corresponds to the inflammatory markers and parameters of hemostasis in COVID-19 patients. In conclusion, inflammation, smoking habit, applied therapy, and chest X rays contribute to a higher level of DNA damage in COVID-19 patients.</jats:p>", "author": [ { "ORCID": "https://orcid.org/0000-0002-5614-210X", "affiliation": [ { "name": "Department of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac , Kragujevac , Serbia" } ], "authenticated-orcid": false, "family": "Mihaljevic", "given": "Olgica", "sequence": "first" }, { "affiliation": [ { "name": "Department of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac , Kragujevac , Serbia" } ], "family": "Zivancevic-Simonovic", "given": "Snezana", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine Faculty of Medical Sciences, University of Kragujevac , Kragujevac , Serbia" }, { "name": "Department of Internal medicine, University Clinical Center Kragujevac , Kragujevac , Serbia" } ], "family": "Cupurdija", "given": "Vojislav", "sequence": "additional" 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