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However, defective clearance of NETs in the lung of acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients could lead to severe respiratory syndrome infection, the so-called coronavirus disease 2019 (COVID-19). To elucidate the pathways that are related to NETs within the pathophysiology of COVID-19, we utilized RNA sequencing (RNA-seq) as well as immunofluorescence and immunohistochemistry methods. RNA-seq analysis provided evidence for increased oxidative stress and the activation of viral-related signaling pathways in post-mortem lungs of COVID-19 patients compared to control donors. Moreover, an excess of neutrophil infiltration and NET formation were detected in the patients\u2019 lungs, where the extracellular DNA was oxidized and co-localized with neutrophil granule protein myeloperoxidase (MPO). Interestingly, staining of the lipid peroxidation marker 4-hydroxynonenal (4-HNE) depicted high colocalization with NETs and was correlated with the neutrophil infiltration of the lung tissues, suggesting that it could serve as a suitable marker for the identification of NETs and the severity of the disease. Moreover, local inhalation therapy to reduce the excess lipid oxidation and NETs in the lungs of severely infected patients might be useful to ameliorate their clinical conditions.<\/jats:p>","DOI":"10.3390\/ijms24032646","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T01:35:45Z","timestamp":1675128945000},"page":"2646","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Transcriptional Insights of Oxidative Stress and Extracellular Traps in Lung Tissues of Fatal COVID-19 Cases"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3703-2009","authenticated-orcid":false,"given":"Aref","family":"Hosseini","sequence":"first","affiliation":[{"name":"Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9243-3759","authenticated-orcid":false,"given":"Darko","family":"Stojkov","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1704-6016","authenticated-orcid":false,"given":"Timoth\u00e9e","family":"Fettrelet","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2344-1349","authenticated-orcid":false,"given":"Rostyslav","family":"Bilyy","sequence":"additional","affiliation":[{"name":"Department of Histology, Cytology and Embryology, Danylo Halytsky Lviv National Medical University, Pekarska Str. 69, 79010 Lviv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9855-4305","authenticated-orcid":false,"given":"Shida","family":"Yousefi","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9404-7736","authenticated-orcid":false,"given":"Hans-Uwe","family":"Simon","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland"},{"name":"Institute of Biochemistry, Brandenburg Medical School, 16816 Neuruppin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lynch, S.M., Guo, G., Gibson, D.S., Bjourson, A.J., and Rai, T.S. 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