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Authors: Weiskopf et al.

Link to paper: https://www.medrxiv.org/content/10.1101/2020.04.11.20062349v1.full.pdf

Journal/ Pre-Print: medRxiv

Key Words: T cells; antigen-specific; Th1; spike protein

Research Highlights 

1. SARS-CoV-2 surface glycoprotein S is a potent T cell immunogen

2. SARS-CoV-2 specific CD4+ T cells in the blood of severe COVID-19 patients are mostly central memory cells.

3. The cytokine profile observed upon re-stimulation of PBMCs is dominated by Th1 cytokines (IFNg, TNFa and IL-2), while Th2 cytokines and Th17 cytokines were only observed at low levels. Of note, an increase in IL-6 is not observed upon stimulation suggesting that IL-6 is predominantly secreted by innate immune cells.

Summary

This preprint assessed the phenotype of SARS-CoV-2 specific T lymphocytes in 8 patients admitted to intensive care (age average 59; mixed genders). Levels of virus-specific IgG and spike protein-specific CD4+ T cells increased over time since ICU admission. More lymphocytes became activated by peptide pools generated from the SARS-CoV-2 spike protein than other viral proteins, suggesting enhanced immunogenicity of the spike protein. This work also shows that SARS-CoV-2-specific CD4 T cells were predominantly of the central memory subset. Their activation was associated with the secretion of Th1-associated cytokines such as IFNg, TNFa and IL-2.

Impact for SARS-CoV2/COVID19 research efforts

A better understanding of the T cell immune response to SARS-CoV2/COVID19

Study Type

· Patient Case study

Strengths and limitations of the paper

Novelty: SARS-CoV-2 spike protein peptides are the target for T cell responses, the differentiation status of Ag-specific CD4+ T cells and the cytokine secretion profile of patient PBMC.

Standing in the field: Similar immunophenotyping papers have been published in China

Appropriate statistics: Yes, for cytokine and activation data (but could be more powered). No statistics for the T cell differentiation status data.

Viral model used: PBMCs from patients tested SARS-CoV-2 positive by RT-PCR were stimulated with peptide pools generated by predicting the epitopes of the SARS-CoV-2 virus based on GenBank reference data.

Translatability: Vaccine design

Main limitations: The results represent a snapshot of the circulating immune system after at least 14 days in the ICU in a relatively small number of patients. No correlation of disease progression with T cell differentiation or composition dynamics. They also assess the differentiation status of CD8 T cells and claim them to be generally more effector-like. However, the only pie chart they are providing to support this claim does not really show a very significant shift towards one predominant phenotype and any supporting statistics are also missing.