SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19
Oksana V. Stanevich, Evgeniia Alekseeva, Maria V. Sergeeva, Artem Fadeev, Kseniya Komissarova, Anna Ivanova, Tamara Simakova, Kirill Vasilyev, Anna-Polina Shurygina, Marina Stukova, Ksenia R. Safina, Elena Nabieva, Sofya K. Garushyants, Galya V. Klink, Evgeny A. Bakin, Jullia V. Zabutova, Anastasia Kholodnaia, О. В. Лукина, Irina A. Skorokhod, V. V. Ryabchikova, Н. В. Медведева, Dmitry Lioznov, Daria Danilenko, Dmitriy M. Chudakov, Andrey B. Komissarov, Georgii A. Bazykin
Abstract
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.