Signature of long-lived memory CD8+ T cells in acute SARS-CoV-2 infection

  1. Sarah Adamo
  2. Jan Michler
  3. Yves Zurbuchen
  4. Carlo Cervia
  5. Patrick Taeschler
  6. Miro E. Raeber
  7. Simona Baghai Sain
  8. Jakob Nilsson
  9. Andreas E. Moor
  10. Onur Boyman

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Abstract

Immunological memory is a hallmark of adaptive immunity and facilitates an accelerated and enhanced immune response upon re-infection with the same pathogen 1,2 . Since the outbreak of the ongoing COVID-19 pandemic, a key question has focused on which SARS-CoV-2-specific T cells stimulated during acute infection give rise to long-lived memory T cells 3 . Here, using spectral flow cytometry combined with cellular indexing of transcriptomes and T cell receptor sequencing, we longitudinally characterized individual SARS-CoV-2-specific CD8 + T cells of patients with COVID-19 from acute infection to 1 year into recovery and found a distinct signature identifying long-lived memory CD8 + T cells. SARS-CoV-2-specific memory CD8 + T cells persisting 1 year after acute infection express CD45RA, IL-7 receptor-α and T cell factor 1, but they maintain low expression of CCR7, thus resembling CD45RA + effector memory T cells. Tracking individual clones of SARS-CoV-2-specific CD8 + T cells, we reveal that an interferon signature marks clones that give rise to long-lived cells, whereas prolonged proliferation and mechanistic target of rapamycin signalling are associated with clonal disappearance from the blood. Collectively, we describe a transcriptional signature that marks long-lived, circulating human memory CD8 + T cells following an acute viral infection.

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  1. Version published to 10.1038/s41586-021-04280-x
  2. ScreenIT

    SciScore for 10.1101/2021.07.22.453029: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Human subjects and patient characteristics: Following written informed consent, adult patients with symptomatic, RT-qPCR confirmed SARS-CoV-2 infection were recruited in the Canton of Zurich, Switzerland, between April 2 and September 24, 2020.
    IRB: The study was approved by the Cantonal Ethics Committee of Zurich (BASEC 2016-01440).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Downstream analysis was conducted in R version 4.1.0 with package Seurat version 4.0.3 (PMID: 34062119).
    Seurat
    suggested: (SEURAT, RRID:SCR_007322)
    TCR profiling on filtered contig annotations was done using R package scRepertoire version 1.1.46, which assigns TCR nucleotide and amino acid sequences together with clonal frequency counts and a clonotype classification to each cell.
    scRepertoire
    suggested: None

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2021.07.22.453029v2 on bioRxiv
  4. Version published to 10.1101/2021.07.22.453029v1 on bioRxiv