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Authors: Fan X. et al.

Link to paper: https://www.medrxiv.org/content/10.1101/2020.05.24.20101238v1

Journal/ Pre-Print: medRxiv

Tags: Immunology/Immunity, Inflammation

Research Highlights 

1. Single-cell transcriptomic analysis of enriched blood T and B cell populations isolated from healthy donors, severe and recovered COVID-19 patients.

2. Severe COVID-19 patients were found to have an overall lower percentage of T cells (lymphopenia) but with highly expressed inflammatory genes.

3. They perform a preliminary single-cell analysis of TCR and BCR variable(V), diversity (D), and joining (J) genes in an attempt to explore the preferential V and J combinations in COVID-19 patients.

Summary 

In this study, they collected the PBMCs of four severe COVID-19 patients, six recovered patients, and three healthy controls. They further isolated CD3-positive and CD19-positive cells through magnetic separation for subsequent single-cell RNA sequencing and V(D)J recombination analysis. Gene ontology analysis of the differentially expressed genes suggested T cell activation in severe patients might persist at early stages of recovery. Trajectory reconstruction results support the differentiation of naïve CD8 T cells into effector and memory cells. The degree of plasmablast and plasma B cell clonal expansion was found to be highest in patients with severe COVID-19. TCR and BCR V(D)J sequences were obtained and used to make some comments on the repertoire.

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19

Study Type

· Ex vivo study

· Clinical Cohort study (13 donors)

Strengths and limitations of the paper

Novelty: Combination of single-cell sequencing and V(D)J recombination analysis on B and T cells in patients at different stages following SARS-CoV-2 infection.

Standing in the field: Lymphopenia and increased plasmablast has been commonly reported in COVID-19 patients.

Appropriate statistics: Weak not well described

Viral model used: SARS-CoV-2 

Translatability: Much more work is required before this can be translatable. The authors suggest that the type specific V(D)J sequences they uncovered from patients with severe COVID, and from those who had recovered from the disease, could provide valuable information for the development of vaccines and immunotherapies.

Main limitations:

· Figure legends are inadequate to properly interrogate the results

· No convincing data supports the claim that cells likely arise from the differentiation of atypical memory B cells.

· The title of this paper mentions V(D)J profiling but they do not provide a thorough analysis simply reporting identification of some sequences.

· The depth of repertoire analysis was too low and not easily attributed to individuals tested.

· Some of the figure legends do not contain enough information to appropriately assess the data.