SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19

Oksana V. Stanevich, Evgeniia I. Alekseeva (), Maria Sergeeva, Artem V. Fadeev, Kseniya S. Komissarova, Anna A. Ivanova, Tamara S. Simakova, Kirill A. Vasilyev, Anna-Polina Shurygina, Marina A. Stukova, Ksenia R. Safina, Elena R. Nabieva, Sofya K. Garushyants, Galya V. Klink, Evgeny A. Bakin, Jullia V. Zabutova, Anastasia N. Kholodnaia, Olga V. Lukina, Irina A. Skorokhod, Viktoria V. Ryabchikova, Nadezhda V. Medvedeva, Dmitry A. Lioznov, Daria M. Danilenko, Dmitriy M. Chudakov, Andrey B. Komissarov and Georgii A. Bazykin ()
Additional contact information
Oksana V. Stanevich: Smorodintsev Research Institute of Influenza
Evgeniia I. Alekseeva: Skolkovo Institute of Science and Technology (Skoltech)
Maria Sergeeva: Smorodintsev Research Institute of Influenza
Artem V. Fadeev: Smorodintsev Research Institute of Influenza
Kseniya S. Komissarova: Smorodintsev Research Institute of Influenza
Anna A. Ivanova: Smorodintsev Research Institute of Influenza
Tamara S. Simakova: Parseq Lab Co. Ltd
Kirill A. Vasilyev: Smorodintsev Research Institute of Influenza
Anna-Polina Shurygina: Smorodintsev Research Institute of Influenza
Marina A. Stukova: Smorodintsev Research Institute of Influenza
Ksenia R. Safina: Skolkovo Institute of Science and Technology (Skoltech)
Elena R. Nabieva: A.A. Kharkevich Institute for Information Transmission Problems of the Russian Academy of Sciences
Sofya K. Garushyants: A.A. Kharkevich Institute for Information Transmission Problems of the Russian Academy of Sciences
Galya V. Klink: A.A. Kharkevich Institute for Information Transmission Problems of the Russian Academy of Sciences
Evgeny A. Bakin: First Pavlov State Medical University
Jullia V. Zabutova: City Hospital 31
Anastasia N. Kholodnaia: First Pavlov State Medical University
Olga V. Lukina: First Pavlov State Medical University
Irina A. Skorokhod: City Hospital 31
Viktoria V. Ryabchikova: City Hospital 31
Nadezhda V. Medvedeva: City Hospital 31
Dmitry A. Lioznov: Smorodintsev Research Institute of Influenza
Daria M. Danilenko: Smorodintsev Research Institute of Influenza
Dmitriy M. Chudakov: Skolkovo Institute of Science and Technology (Skoltech)
Andrey B. Komissarov: Smorodintsev Research Institute of Influenza
Georgii A. Bazykin: Skolkovo Institute of Science and Technology (Skoltech)

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-022-34033-x

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