{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:14:37Z","timestamp":1789730077165,"version":"4.0.1"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,15]],"date-time":"2022-10-15T00:00:00Z","timestamp":1665792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Bia\u0142ystok, Poland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Thorough understanding of metabolic changes, including lipidome alteration, associated with the development of COVID-19 appears to be crucial, as new types of coronaviruses are still reported. In this study, we analyzed the differences in the plasma phospholipid profiles of the deceased COVID-19 patients, those who recovered and healthy people. Due to identified abnormalities in plasma phospholipid profiles, deceased patients were further divided into two subgroups (D1 and D2). Increased levels of phosphatidylethanolamines (PE), phosphatidylcholines (PC) and phosphatidylserines (PS) were found in the plasma of recovered patients and the majority of deceased patients (first subgroup D1) compared to the control group. However, abundances of all relevant PE, PC and PS species decreased dramatically in the plasma of the second subgroup (D2) of five deceased patients. These patients also had significantly decreased plasma COX-2 activity when compared to the control, in contrast to unchanged and increased COX-2 activity in the plasma of the other deceased patients and recovered patients, respectively. Moreover, these five deceased patients were characterized by abnormally low CRP levels and tremendous increase in LDH levels, which may be the result of other pathophysiological disorders, including disorders of the immune system, liver damage and haemolytic anemia. In addition, an observed trend to decrease the autoantibodies against oxidative modifications of low-density lipoprotein (oLAb) titer in all, especially in deceased patients, indicate systemic oxidative stress and altered immune system that may have prognostic value in COVID-19.<\/jats:p>","DOI":"10.3390\/biom12101488","type":"journal-article","created":{"date-parts":[[2022,10,16]],"date-time":"2022-10-16T21:10:10Z","timestamp":1665954610000},"page":"1488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Lipidomics Revealed Plasma Phospholipid Profile Differences between Deceased and Recovered COVID-19 Patients"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5032-0369","authenticated-orcid":false,"given":"Neven","family":"\u017darkovi\u0107","sequence":"first","affiliation":[{"name":"Ru\u0111er Bo\u0161kovi\u0107 Institute, Laboratory for Oxidative Stress, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biserka","family":"Orehovec","sequence":"additional","affiliation":[{"name":"Clinical Hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Bar\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Clinical Hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4173-1278","authenticated-orcid":false,"given":"Marko","family":"Tarle","sequence":"additional","affiliation":[{"name":"Clinical Hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Kmet","sequence":"additional","affiliation":[{"name":"Clinical Hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9138-2037","authenticated-orcid":false,"given":"Ivica","family":"Luk\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Clinical Hospital Dubrava, 10000 Zagreb, Croatia"},{"name":"Department of Pathology, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Tatzber","sequence":"additional","affiliation":[{"name":"Omnignostica Ltd., 3421 H\u00f6flein an der Donau, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7171-9539","authenticated-orcid":false,"given":"Willibald","family":"Wonisch","sequence":"additional","affiliation":[{"name":"Omnignostica Ltd., 3421 H\u00f6flein an der Donau, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5397-7139","authenticated-orcid":false,"given":"El\u017cbieta","family":"Skrzydlewska","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Medical University of Bialystok, A. Mickiewicza 2D, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3992-1910","authenticated-orcid":false,"given":"Wojciech","family":"\u0141uczaj","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Medical University of Bialystok, A. Mickiewicza 2D, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0140-6736(03)13967-0","article-title":"Newly Discovered Coronavirus as the Primary Cause of Severe Acute Respiratory Syndrome","volume":"362","author":"Kuiken","year":"2003","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1056\/NEJMoa2001316","article-title":"Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia","volume":"382","author":"Li","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","unstructured":"(2022, March 29). WHO Coronavirus (COVID-19) Dashboard. Available online: https:\/\/covid19.who.int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1148\/radiol.2020200269","article-title":"Evolution of CT Manifestations in a Patient Recovered from 2019 Novel Coronavirus (2019-NCoV) Pneumonia in Wuhan, China","volume":"295","author":"Shi","year":"2020","journal-title":"Radiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S2213-2600(20)30079-5","article-title":"Clinical Course and Outcomes of Critically Ill Patients with SARS-CoV-2 Pneumonia in Wuhan, China: A Single-Centered, Retrospective, Observational Study","volume":"8","author":"Yang","year":"2020","journal-title":"Lancet. Respir. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1038\/cdd.2015.122","article-title":"The Phospholipid Code: A Key Component of Dying Cell Recognition, Tumor Progression and Host\u2013Microbe Interactions","volume":"22","author":"Baxter","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3934\/molsci.2019.1.1","article-title":"Phospholipid\u2014The Dynamic Structure between Living and Non-Living World; a Much Obligatory Supramolecule for Present and Future","volume":"6","author":"Alagumuthu","year":"2019","journal-title":"AIMSMOLES"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cai, T., and Yang, F. (2018). Phospholipid and Phospholipidomics in Health and Diseases. Lipidomics in Health & Disease, Springer.","DOI":"10.1007\/978-981-13-0620-4_11"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Du, Y., Mi, Z., Xie, Y., Lu, D., Zheng, H., Sun, H., Zhang, M., and Niu, Y. (2021). Insights into the Molecular Basis of Tick-Borne Encephalitis from Multiplatform Metabolomics. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009172"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.chom.2017.10.011","article-title":"Multi-Platform \u2019Omics Analysis of Human Ebola Virus Disease Pathogenesis","volume":"22","author":"Eisfeld","year":"2017","journal-title":"Cell Host Microbe."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.1073\/pnas.1815356116","article-title":"Plasma Lipidome Reveals Critical Illness and Recovery from Human Ebola Virus Disease","volume":"116","author":"Kyle","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"\u017darkovi\u0107, N., Orehovec, B., Milkovi\u0107, L., Bar\u0161i\u0107, B., Tatzber, F., Wonisch, W., Tarle, M., Kmet, M., Matai\u0107, A., and Jakov\u010devi\u0107, A. (2021). Preliminary Findings on the Association of the Lipid Peroxidation Product 4-Hydroxynonenal with the Lethal Outcome of Aggressive COVID-19. Antioxidants, 10.","DOI":"10.3390\/antiox10091341"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A Simple Method for the Isolation and Purification of Total Lipides from Animal Tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0003-2697(70)90343-X","article-title":"Spectrophotometric Determination of Phosphate Esters in the Presence and Absence of Orthophosphate","volume":"36","author":"Bartlett","year":"1970","journal-title":"Anal. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"\u0141uczaj, W., Dobrzy\u0144ska, I., Wro\u0144ski, A., Domingues, M.R., Domingues, P., and Skrzydlewska, E. (2020). Cannabidiol-Mediated Changes to the Phospholipid Profile of UVB-Irradiated Keratinocytes from Psoriatic Patients. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186592"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.abb.2018.07.021","article-title":"Plasma Lipidomic Profile Signature of Rheumatoid Arthritis versus Lyme Arthritis Patients","volume":"654","author":"Domingues","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"24019","DOI":"10.1074\/jbc.270.41.24019","article-title":"Comparison of Hydroperoxide Initiator Requirements for the Cyclooxygenase Activities of Prostaglandin H Synthase-1 and -2","volume":"270","author":"Kulmacz","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1620\/tjem.210.247","article-title":"Persistent Oxidative Stress after Myocardial Infarction Treated by Percutaneous Coronary Intervention","volume":"210","author":"Rabuzin","year":"2006","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.freeradbiomed.2018.05.051","article-title":"Antibody against Low Density Lipoproteins (OLAb), Procalcitonin and Neopterin as Prognostic Marker during Sepsis and Systemic Inflammatory Response Syndrome (SIRS)","volume":"124","author":"Reiger","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pluskal, T., Castillo, S., Villar-Briones, A., and Ore\u0161i\u010d, M. (2010). MZmine 2: Modular Framework for Processing, Visualizing, and Analyzing Mass Spectrometry-Based Molecular Profile Data. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-395"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.1002\/cpbi.86","article-title":"Using MetaboAnalyst 4.0 for Comprehensive and Integrative Metabolomics Data Analysis","volume":"68","author":"Chong","year":"2019","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zarkovic, N., Jakovcevic, A., Mataic, A., Jaganjac, M., Vukovic, T., Waeg, G., and Zarkovic, K. (2022). Post-Mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19. Cells, 11.","DOI":"10.3390\/cells11030444"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/jb\/mvs092","article-title":"Mediator Lipidomics in Acute Inflammation and Resolution","volume":"152","author":"Arita","year":"2012","journal-title":"J. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4526","DOI":"10.1039\/C8AN01046C","article-title":"Lipid Metabolism in Inflammation-Related Diseases","volume":"143","author":"Zhang","year":"2018","journal-title":"Analyst"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17714","DOI":"10.1038\/s41598-019-53721-1","article-title":"Plasma Lipid Profiles Discriminate Bacterial from Viral Infection in Febrile Children","volume":"9","author":"Wang","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Barberis, E., Timo, S., Amede, E., Vanella, V.V., Puricelli, C., Cappellano, G., Raineri, D., Cittone, M.G., Rizzi, E., and Pedrinelli, A.R. (2020). Large-Scale Plasma Analysis Revealed New Mechanisms and Molecules Associated with the Host Response to SARS-CoV-2. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228623"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kaur, G., Ji, X., and Rahman, I. (2021). SARS-CoV2 Infection Alters Tryptophan Catabolism and Phospholipid Metabolism. Metabolites, 11.","DOI":"10.3390\/metabo11100659"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1159\/000489504","article-title":"Unique Francisella Phosphatidylethanolamine Acts as a Potent Anti-Inflammatory Lipid","volume":"10","author":"Ireland","year":"2018","journal-title":"J. Innate. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"120489","DOI":"10.1016\/j.lfs.2022.120489","article-title":"The Effect of Polyunsaturated Fatty Acids on the Severity and Mortality of COVID Patients: A Systematic Review","volume":"299","author":"Mazidimoradi","year":"2022","journal-title":"Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"106619","DOI":"10.1016\/j.prostaglandins.2022.106619","article-title":"The Function of Specialized Pro-Resolving Endogenous Lipid Mediators, Vitamins, and Other Micronutrients in the Control of the Inflammatory Processes: Possible Role in Patients with SARS-CoV-2 Related Infection","volume":"159","author":"Gallo","year":"2022","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.freeradbiomed.2010.10.709","article-title":"Formation of 4-hydroxynonenal from cardiolipin oxidation: Intramolecular peroxyl radical addition and decomposition","volume":"50","author":"Liu","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"20831","DOI":"10.1074\/jbc.M101821200","article-title":"Two Distinct Pathways of Formation of 4-Hydroxynonenal: Mechanisms of nonenzymatic transformation of the 9- and 13-hydroperoxides of linoleic acid to 4-hydroxyalkenals*","volume":"276","author":"Schneider","year":"2001","journal-title":"J. Bio. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.freeradbiomed.2016.11.033","article-title":"Antioxidants and HNE in Redox Homeostasis","volume":"111","author":"Skrzydlewska","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"230","DOI":"10.2174\/09298673113209990181","article-title":"4-Hydroxynonenal in the Pathogenesis and Progression of Human Diseases","volume":"21","author":"Shoeb","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.redox.2014.11.011","article-title":"Functional Interaction between Cyclooxygenase-2 and P53 in Response to an Endogenous Electrophile","volume":"4","author":"Kumagai","year":"2014","journal-title":"Redox. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1194\/jlr.R800042-JLR200","article-title":"Cyclooxygenases: Structural and Functional Insights","volume":"50","author":"Rouzer","year":"2009","journal-title":"J. Lipid. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/s12964-020-00687-7","article-title":"Phosphatidylserine inside out: A Possible Underlying Mechanism in the Inflammation and Coagulation Abnormalities of COVID-19","volume":"18","author":"Palmeira","year":"2020","journal-title":"Cell Commun. Signal."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e02079-20","DOI":"10.1128\/JVI.02079-20","article-title":"Phosphatidylethanolamine and Phosphatidylserine Synergize to Enhance GAS6\/AXL-Mediated Virus Infection and Efferocytosis","volume":"95","author":"Zhang","year":"2020","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.chom.2012.08.009","article-title":"The TIM and TAM Families of Phosphatidylserine Receptors Mediate Dengue Virus Entry","volume":"12","author":"Meertens","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8327","DOI":"10.1128\/JVI.01025-13","article-title":"Role of the Phosphatidylserine Receptor TIM-1 in Enveloped-Virus Entry","volume":"87","author":"Kondratowicz","year":"2013","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/s41569-021-00552-1","article-title":"Interplay between Inflammation and Thrombosis in Cardiovascular Pathology","volume":"18","author":"Stark","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cca.2020.06.012","article-title":"Lactate Dehydrogenase and C-Reactive Protein as Predictors of Respiratory Failure in COVID-19 Patients","volume":"509","author":"Poggiali","year":"2020","journal-title":"Clin. Chim. Acta."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"221","DOI":"10.14740\/jh906","article-title":"Hemolytic Anemia Complicating COVID-19 Infection","volume":"10","author":"AbouYabis","year":"2021","journal-title":"J. Hematol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"276","DOI":"10.4103\/sjmms.sjmms_203_21","article-title":"COVID-19-Associated Severe Autoimmune Hemolytic Anemia: A Rare Case Report","volume":"9","author":"Nair","year":"2021","journal-title":"Saudi. J. Med. Med. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"754","DOI":"10.3389\/fimmu.2018.00754","article-title":"Role of C-Reactive Protein at Sites of Inflammation and Infection","volume":"9","author":"Sproston","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/trf.16226","article-title":"COVID-19 Associated with Severe Autoimmune Hemolytic Anemia","volume":"61","author":"Jacobs","year":"2021","journal-title":"Transfusion"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/bjh.16794","article-title":"Autoimmune Haemolytic Anaemia Associated with COVID-19 Infection","volume":"190","author":"Lazarian","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/bjh.16786","article-title":"Simultaneous Onset of COVID-19 and Autoimmune Haemolytic Anaemia","volume":"190","author":"Lopez","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e28382","DOI":"10.1002\/pbc.28382","article-title":"COVID-19 Presenting with Autoimmune Hemolytic Anemia in the Setting of Underlying Immune Dysregulation","volume":"67","author":"Wahlster","year":"2020","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"635670","DOI":"10.1155\/2015\/635670","article-title":"Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia","volume":"2015","author":"Barcellini","year":"2015","journal-title":"Dis. 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