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Authors: Le Bert et al

Link to paper:

Journal/ Pre-Print: Biorxiv

Tags: Immunology/Immunity

Research Highlights

1. Evaluate pre-existing memory towards SARS-CoV2 nucleaocapsid protein (NP) and non-structural proteins (NSP); in people with no history of COVID-19 and in convalescent patients.

2. T-cells from SARS (2003) and COVID-19 patients share similar antigen responsiveness to conserved regions of NP but not NSP7/13.

3. Virus-naïve donors show a different pool of reactive T-cells to NP and enhanced reactivity to NSP7/13.


T-cell responses towards the nucleocapsid protein (NP) and the highly conserved NSP7 & 13 were assessed between naïve and SARS-Cov1/2 infected patients. Using 215 15-mer peptides they covered the whole span of the proteins. They detected responsive cells through cytokine production in recovered patients mainly against NP. Long term T cell memory from recovered SARS patients and similar antigen recognition between SARS/COVID-19 patients indicates a potential for cross-reactivity and long-term memory. Virus-naïve donors had a different pattern (more widely) reactive cells to NP and NSP, possibly indicating a better chance of aborting infection before it is established.

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19

Study Type

· In vitro study

· Patient Case study

Strengths and limitations of the paper

Novelty: Comprehensive analysis of memory responses and cross-reactivity to SARS-CoV2

Standing in the field: People have already reported “pre-existing” memory to SARS-CoV2, most likely through historical exposure to other betacoronaviruses. This is the first study that examines memory with respect to nucleocapsid protein rather than Spike.

Appropriate statistics: A reasonable number of patients (65 across all groups). No other statistics were used.

Viral model used: People with COVID-19 diagnosis or previous SARS infection. Mainly synthetic peptides.

Translatability: It provides an understanding of the potential cross-reactivity and factors contributing to susceptibility and possible long-term memory. No direct link to translation. Although a vaccine specific to ORF-1 (NSP) proteins which are more conserved across different coronaviruses might prove a promising approach.

Main limitations: Peptide library size choice is probably more tuned to identify MHCII restricted peptides and hence CD4 responses, although they also show CD8 activation. It would be interesting to see the outcome if smaller peptides were used (more CD8 clones?). It would also be good to see single cell reactivity through tetramer staining, to identify any potential bystander effects contributing to cytokine signal. The subjects were biased towards the Asian population, with less than 40% Caucasians in each group, it would be interesting to see if the same conclusions hold with different demographic background.