Khatamzas, E., Antwerpen, M. H., Rehn, A., Graf, A., Hellmuth, J. C., Hollaus, A., Mohr, A. W., Gaitzsch, E., Weiglein, T., Georgi, E., Scherer, C., Stecher, S. S., Gruetzner, S., Blum, H., Krebs, S., Reischer, A., Leutbecher, A., Subklewe, M., Dick, A., Zange, S., Girl, P., Müller, K., Weigert, O., Hopfner, K. P., Stemmler, H. J., von Bergwelt-Baildon, M., Keppler, O. T., Wölfel, R., Muenchhoff, M., Moosmann, A. (2022). Nat Commun 13, 5586.
DOI:10.1038/s41467-022-32772-5
Antibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection. Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately fatal infection, and identify three mutations in the spike protein that dampen convalescent plasma-mediated neutralization of SARS-CoV-2. Additionally, four mutations emerge in non-spike regions encoding three CD8 T cell epitopes, including one nucleoprotein epitope affected by two mutations. Recognition of each mutant peptide by CD8 T cells from convalescent donors is reduced compared to its ancestral peptide, with additive effects resulting from double mutations. Querying public SARS-CoV-2 sequences shows that these mutations have independently emerged as homoplasies in circulating lineages. Our data thus suggest that potential impacts of CD8 T cells on SARS-CoV-2 mutations, at least in those with humoral immunodeficiency, warrant further investigation to inform on vaccine design.
