COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However, neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T-cell response nor the diversity of resulting immune memory is well understood. In this study, we use longitudinal high-throughput T-cell receptor (TCR) sequencing to track changes in the T-cell repertoire following two mild cases of COVID-19. In both donors, we identified CD4+ and CD8+ T-cell clones with transient clonal expansion after infection. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurrence of these motifs in publicly available large dataset of repertoires from COVID-19 patients. We show that in both donors, the majority of infection-reactive clonotypes acquire memory phenotypes. Certain T-cell clones were detected in the memory fraction at the pre-infection time point, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.

5 1 Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology Moscow Russian Federation

Institute of Clinical Molecular Biology Kiel University Kiel Germany

Laboratoire de physique de l'École Normale Supérieure ENS PSL Sorbonne Universite Universite de Paris and CNRS Paris France

Masaryk University Central European Institute of Technology Brno Czech Republic

Moscow State University Moscow Russian Federation

National Research Center for Hematology Moscow Russian Federation

Pirogov Russian National Research Medical University Moscow Russian Federation

Shemyakin Ovchinnikov Institute of Bioorganic Chemistry Moscow Russian Federation

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