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dc.contributor.authorOlsen, Maria Belland
dc.contributor.authorHuse, Camilla
dc.contributor.authorSousa, Mirta
dc.contributor.authorMurphy, Sarah Louise Mikalsen
dc.contributor.authorSarno, Antonio
dc.contributor.authorObermann, Tobias Sebastian
dc.contributor.authorYang, Kuan
dc.contributor.authorHolter, Jan Cato
dc.contributor.authorJørgensen, Marthe Jøntvedt
dc.contributor.authorChristensen, Erik Egeland
dc.contributor.authorWang, Wei
dc.contributor.authorJi, Ping
dc.contributor.authorHeggelund, Lars
dc.contributor.authorHoel, Hedda
dc.contributor.authorDyrhol-Riise, Anne Ma
dc.contributor.authorGregersen, Ida
dc.contributor.authorAukrust, Pål
dc.contributor.authorBjørås, Magnar
dc.contributor.authorHalvorsen, Bente
dc.contributor.authorDahl, Tuva Børresdatter
dc.identifier.citationJournal of Inflammation Research. 2022, 15, 6629-6644.en_US
dc.description.abstractPurpose: 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.en_US
dc.rightsNavngivelse-Ikkekommersiell 4.0 Internasjonal*
dc.titleDNA Repair Mechanisms are Activated in Circulating Lymphocytes of Hospitalized Covid-19 Patientsen_US
dc.title.alternativeDNA Repair Mechanisms are Activated in Circulating Lymphocytes of Hospitalized Covid-19 Patientsen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.source.journalJournal of Inflammation Researchen_US
dc.relation.projectNorges forskningsråd: 312780en_US
dc.relation.projectHelse Sør-Øst RHF: 2021071en_US

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Navngivelse-Ikkekommersiell 4.0 Internasjonal
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