SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19.
Oksana V StanevichEvgeniia I AlekseevaMariia V SergeevaArtem V FadeevKseniya S KomissarovaAnna A IvanovaTamara S SimakovaKirill A VasilyevAnna-Polina ShuryginaMarina A StukovaKsenia R SafinaElena R NabievaSofya K GarushyantsGalya V KlinkEvgeny A BakinJullia V ZabutovaAnastasia N KholodnaiaOlga V LukinaIrina A SkorokhodViktoria V RyabchikovaNadezhda V MedvedevaDmitry A LioznovDaria M DanilenkoDmitriy M ChudakovAndrey B KomissarovGeorgii A BazykinPublished in: Nature communications (2023)
Evolution of SARS-CoV-2 in immunocompromised hosts may result in novel variants with changed properties. While escape from humoral immunity certainly contributes to intra-host evolution, escape from cellular immunity is poorly understood. Here, we report a case of long-term COVID-19 in an immunocompromised patient with non-Hodgkin's lymphoma who received treatment with rituximab and lacked neutralizing antibodies. Over the 318 days of the disease, the SARS-CoV-2 genome gained a total of 40 changes, 34 of which were present by the end of the study period. Among the acquired mutations, 12 reduced or prevented the binding of known immunogenic SARS-CoV-2 HLA class I antigens. By experimentally assessing the effect of a subset of the escape mutations, we show that they resulted in a loss of as much as ~1% of effector CD8 T cell response. Our results indicate that CD8 T cell escape represents a major underappreciated contributor to SARS-CoV-2 evolution in humans.