Signature of long-lived memory CD8+ T cells in acute SARS-CoV-2 infection
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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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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
Ethics Consent: 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 variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Downstream analysis was conducted in R version 4.1.0 with package Seurat version 4.0.3 (PMID: 34062119). Seuratsuggested: (SEURAT, RRID:SCR_007322)TCR profiling on filtered contig … 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
Ethics Consent: 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 variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Downstream analysis was conducted in R version 4.1.0 with package Seurat version 4.0.3 (PMID: 34062119). Seuratsuggested: (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. scRepertoiresuggested: NoneResults 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.
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