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Authors: A. Ganji et al.

Link to paper: https://www.ncbi.nlm.nih.gov/research/coronavirus/publication/32325421

Journal/ Pre-Print: Blood Cells, Molecules, and Diseases

Tags: COVID-19, CD4 T cells, CD8 T cells, clinical immunology

· Clinical

· Immunology/Immunity

Research Highlights 

1. Peripheral white blood cells, platelet, and lymphocyte counts were significantly decreased in severe COVID-19 patients compared to healthy donors (age and sex-matched).

2. CD4:CD8 ratio and CD4 and CD8+ lymphocyte frequency did not show significant differences in COVID-19 patients compared to healthy donors

3. CD8 MFI was significantly increased in COVID-19 patients compared to HC indicating CD8 overexpression.

Summary

Venous blood samples were taken from 25 COVID-19 infected patients who were hospitalized in the ICU. Blood cells were analysed showing a significant decrease in the number of white blood cells, lymphocytes, and platelets in COVID-19 patients compared to healthy donors. Lymphocytes were further analysed using flow cytometry, showing no differences between CD4:CD8 ratio neither CD4 and CD8+ lymphocyte frequencies. However, this study found an increase in the CD8 expression on individual cells of COVID-19 patients compared to HC by looking at the MFI. The authors suggest that this overexpression could indicate hyperactivation of cytotoxic cells antiviral response.

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19

Study Type

· Patient Case study

Strengths and limitations of the paper

Novelty: This study did not provide new insights as numbers of white blood cells have already been investigated by other groups. This study refers to studies that found the same results and does not add anything novel except for the increased MFI of CD8 in patients.

Standing in the field: Several papers support the findings of this study.

Appropriate statistics: The power of this study is sufficient (n=25) matching with the control group (n=25), matched to age and sex. The study uses the Standard Deviation and t-test which is appropriate using two groups with normal distributions.

Viral model used: The original SARS-CoV2 strain was studied.

Translatability: There is no immediate translational potential arising from this study.

Main limitations:

- They did not specify the type of patients included in the study (ICU patients in serious conditions). It would give the paper more strength if it could compare ICU patients to non-hospitalized patients or a time-course.

- They did not specify when they harvest the blood samples: symptomatic patients? Positive PCR? Day post-hospitalization etc.

- This study only uses one technique (flow cytometry), they compared MFI but did not provide full methodological details. In addition, it would have been more appropriate to have put the different MFI on the same gate and normalize to the mode to appreciate the difference.

- They only assessed the CD4:CD8 ratio and did not go into detail. It would also have been interesting to look at the Treg:CD8 ratio for example.

- They did not assess the activation profile of the CD8 T cells. Although they detected increased CD8 expression, it would worthwhile to determine by FACS whether the CD8 T cells were activated and showed evidence of encounter with antigen.

- It would also have been informative to have measured the secretion of cytokines by the cells.