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dc.contributor.authorThomas, Tiffany
dc.contributor.authorStefanoni, Davide
dc.contributor.authorDzieciatkowska, Monika
dc.contributor.authorIssaian, Aaron
dc.contributor.authorNemkov, Travis
dc.contributor.authorHill, Ryan C
dc.contributor.authorFrancis, Richard O
dc.contributor.authorHudson, Krystalyn E
dc.contributor.authorBuehler, Paul W
dc.contributor.authorZimring, James C
dc.contributor.authorHod, Eldad A
dc.contributor.authorHansen, Kirk C
dc.contributor.authorSpitalnik, Steven L
dc.contributor.authorD'Alessandro, Angelo
dc.date.accessioned2020-11-18T19:22:38Z
dc.date.available2020-11-18T19:22:38Z
dc.date.issued2020-10-26
dc.identifier.urihttp://hdl.handle.net/10713/14121
dc.description.abstractThe SARS-CoV-2 beta coronavirus is the etiological driver of COVID-19 disease, which is primarily characterized by shortness of breath, persistent dry cough, and fever. Because they transport oxygen, red blood cells (RBCs) may play a role in the severity of hypoxemia in COVID-19 patients. The present study combines state-of-the-art metabolomics, proteomics, and lipidomics approaches to investigate the impact of COVID-19 on RBCs from 23 healthy subjects and 29 molecularly diagnosed COVID-19 patients. RBCs from COVID-19 patients had increased levels of glycolytic intermediates, accompanied by oxidation and fragmentation of ankyrin, spectrin beta, and the N-terminal cytosolic domain of band 3 (AE1). Significantly altered lipid metabolism was also observed, in particular, short- and medium-chain saturated fatty acids, acyl-carnitines, and sphingolipids. Nonetheless, there were no alterations of clinical hematological parameters, such as RBC count, hematocrit, or mean corpuscular hemoglobin concentration, with only minor increases in mean corpuscular volume. Taken together, these results suggest a significant impact of SARS-CoV-2 infection on RBC structural membrane homeostasis at the protein and lipid levels. Increases in RBC glycolytic metabolites are consistent with a theoretically improved capacity of hemoglobin to off-load oxygen as a function of allosteric modulation by high-energy phosphate compounds, perhaps to counteract COVID-19-induced hypoxia. Conversely, because the N-terminus of AE1 stabilizes deoxyhemoglobin and finely tunes oxygen off-loading and metabolic rewiring toward the hexose monophosphate shunt, RBCs from COVID-19 patients may be less capable of responding to environmental variations in hemoglobin oxygen saturation/oxidant stress when traveling from the lungs to peripheral capillaries and vice versa.en_US
dc.description.urihttps://doi.org/10.1021/acs.jproteome.0c00606en_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.ispartofJournal of Proteome Researchen_US
dc.subjectAE1en_US
dc.subjectSARS-CoV-2en_US
dc.subjectband 3en_US
dc.subjecterythrocyteen_US
dc.subjectlipidomicsen_US
dc.subjectmetabolomicsen_US
dc.subjectproteomicsen_US
dc.titleEvidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells from COVID-19 Patientsen_US
dc.typeArticleen_US
dc.identifier.doi10.1021/acs.jproteome.0c00606
dc.identifier.pmid33103907
dc.source.volume19
dc.source.issue11
dc.source.beginpage4455
dc.source.endpage4469
dc.source.countryUnited States


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