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Evidence for structural protein damage and membrane lipid remodeling in red blood cells from COVID-19 patients.
medRxiv. 2020 Jun 30M

Abstract

The 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, especially 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, and 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, RBCs from COVID-19 patients may be incapable of responding to environmental variations in hemoglobin oxygen saturation when traveling from the lungs to peripheral capillaries and, as such, may have a compromised capacity to transport and deliver oxygen.

Authors

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Pub Type(s)

Preprint

Language

eng

PubMed ID

32637980

Citation

Thomas, Tiffany, et al. "Evidence for Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells From COVID-19 Patients." MedRxiv : the Preprint Server for Health Sciences, 2020.
Thomas T, Stefanoni D, Dzieciatkowska M, et al. Evidence for structural protein damage and membrane lipid remodeling in red blood cells from COVID-19 patients. medRxiv. 2020.
Thomas, T., Stefanoni, D., Dzieciatkowska, M., Issaian, A., Nemkov, T., Hill, R. C., Francis, R. O., Hudson, K. E., Buehler, P. W., Zimring, J. C., Hod, E. A., Hansen, K. C., Spitalnik, S. L., & D'Alessandro, A. (2020). Evidence for structural protein damage and membrane lipid remodeling in red blood cells from COVID-19 patients. MedRxiv : the Preprint Server for Health Sciences. https://doi.org/10.1101/2020.06.29.20142703
Thomas T, et al. Evidence for Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells From COVID-19 Patients. medRxiv. 2020 Jun 30; PubMed PMID: 32637980.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for structural protein damage and membrane lipid remodeling in red blood cells from COVID-19 patients. AU - Thomas,Tiffany, AU - Stefanoni,Davide, AU - Dzieciatkowska,Monika, AU - Issaian,Aaron, AU - Nemkov,Travis, AU - Hill,Ryan C, AU - Francis,Richard O, AU - Hudson,Krystalyn E, AU - Buehler,Paul W, AU - Zimring,James C, AU - Hod,Eldad A, AU - Hansen,Kirk C, AU - Spitalnik,Steven L, AU - D'Alessandro,Angelo, Y1 - 2020/06/30/ PY - 2020/7/9/entrez PY - 2020/7/9/pubmed PY - 2020/7/9/medline JF - medRxiv : the preprint server for health sciences JO - medRxiv N2 - The 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, especially 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, and 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, RBCs from COVID-19 patients may be incapable of responding to environmental variations in hemoglobin oxygen saturation when traveling from the lungs to peripheral capillaries and, as such, may have a compromised capacity to transport and deliver oxygen. UR - https://www.unboundmedicine.com/medline/citation/32637980/Evidence_for_structural_protein_damage_and_membrane_lipid_remodeling_in_red_blood_cells_from_COVID_19_patients_ L2 - https://doi.org/10.1101/2020.06.29.20142703 DB - PRIME DP - Unbound Medicine ER -
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