Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells from COVID-19 Patients

• Published in: Journal of proteome research Vol. 19; no. 11; pp. 4455 - 4469
• Main Authors: Thomas, Tiffany, Stefanoni, Davide, Dzieciatkowska, Monika, Issaian, Aaron, Nemkov, Travis, Hill, Ryan C, Francis, Richard O, Hudson, Krystalyn E, Buehler, Paul W, Zimring, James C, Hod, Eldad A, Hansen, Kirk C, Spitalnik, Steven L, D’Alessandro, Angelo
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 06.11.2020
• Subjects: Betacoronavirus; Coronavirus Infections - blood; Coronavirus Infections - pathology; Coronavirus Infections - physiopathology; cough; COVID-19; COVID-19 infection; dyspnea; erythrocyte count; Erythrocytes - chemistry; Erythrocytes - cytology; Erythrocytes - pathology; etiology; fever; glycolysis; hematocrit; hemoglobin; homeostasis; Humans; hypoxia; lipid metabolism; Lipidomics; Membrane Lipids - analysis; Membrane Lipids - chemistry; Membrane Lipids - metabolism; Membrane Proteins - analysis; Membrane Proteins - chemistry; Membrane Proteins - metabolism; metabolites; Metabolome - physiology; Models, Molecular; oxidants; oxidation; oxygen; Pandemics; phosphates; Pneumonia, Viral - blood; Pneumonia, Viral - pathology; Pneumonia, Viral - physiopathology; proteome; Proteome - analysis; Proteome - chemistry; Proteome - metabolism; proteomics; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; spectrin; sphingolipids; structural proteins; SARS-CoV-2; proteomics; metabolomics; band 3; AE1; lipidomics; erythrocyte
• ISSN: 1535-3893; 1535-3907; 1535-3907
• DOI: 10.1021/acs.jproteome.0c00606

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, 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.