Despite no significant changes in the total levels of key structural proteins (e.g., band 3: AE1; spectrin alpha: SPTA1; ankyrin: ANK1; A), peptidomics analyses showed significant increases and decreases in specific peptides from these proteins (heat map in B shows the top 50 significant changes by t-test). Further analysis of AE1 identified significant increases in levels of the peptide spanning amino acid residues 57-74, in contrast to decreased levels of the N-terminal 1-57 peptide (C), as mapped (red) against the pdb:1hyn spanning residues 56-346 of AE2 (grey; D). In addition, in COVID-19 patients, RBC AE1 was significantly more oxidized (M oxidation + N/Q deamidation) than in control RBCs (E), in the absence of detectable changes in the levels of peptides beyond residue 75 (F). Similar increases in the levels and oxidation of peptides for SPTA1 (G) and ANK1 (H) were observed, consistent with an effect of COVID-19 on the integrity of RBC structural membrane proteins (I).