Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection
Anastasia A. Minervina1, Ekaterina A. Komech1,2, Aleksei Titov3, Meriem Bensouda Koraichi4, Elisa Rosati5, Ilgar Z. Mamedov1,2,6,7, Andre Franke5, Grigory A. Efimov3, Dmitriy M. Chudakov1,2,6,8, Thierry Mora4, Aleksandra M. Walczak4, Yuri B. Lebedev1,9, Mikhail V. Pogorelyy
Link to paper: https://doi.org/10.1101/2020.05.18.100545
Journal/ Pre-Print: MedRxiv
1. Longitudinal characterisation of T cell clones in two mild COVID-19 patients.
2. Identification of pre-existing T-cell memory clones mediating response
3. Description of TCR sequences motifs of SARS-CoV-2 reactive clones
TCR clonal dynamics of two mild cases of COVID-19 are reported. Samples from day 12 following symptoms onset were collected for a month. They identify expanding (mainly CD4+) and contracting (CD8+, CD4+) clones following the infection. The clones occupied different compartments of the memory pool with CD8+ biased towards EMRA. A low number of the reactive clones was identified in a pre-infection sample indicating cross-reactivity with other infections. Shared TCR motifs suggest a potential immunodominant antigen.
Impact for SARS-CoV2/COVID19 research efforts
Description of TCR sequence motifs of SARS-CoV-2 reactive clones.
· Ex vivo study (mild COVID-19 patient samples)
Strengths and limitations of the paper
Novelty: Identify SARS-CoV2 reactive T-cell clones
Standing in the field: There is an increasing body of work trying to identify virus-specific T cell responses, from identifying antigens (through peptide library screening) to the identification of T cell clones.
Appropriate statistics: Sample size is inadequate as it contains only two mild cases. However, the analysis and statistics for each case is well performed using multiple tools to validate the conclusions.
Viral model used: Clinical samples.
Translatability: Potential use for T-cell therapies. Further work on ex vivo expansion and recovery of T cells from SARS-CoV-2-convalescent donors with sufficient enrichment of viral-specific effector memory T cells would be needed.
Main limitations: Data collected from two donors, which seem to be related (same household). No other disease states (such as severe or asymptomatic cases). Analysis was done on bulk populations, so the phenotypic characterisation is correlative; scRNA would have been a better approach to correlate the clonality and the phenotype. Intriguing expansion of CD8+ EMRA clones that is not thoroughly discussed. Cross-reactive clones only discovered in the CD4+ population.