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Authors: Liu et al.

Link to paper: https://www.ncbi.nlm.nih.gov/research/coronavirus/publication/32361250

Journal/ Pre-Print: EBioMedicine

Tags : Immunology/Immunity, Clinical/ Diagnostics, Inflammation

Research Highlights 

1. Lower lymphocyte counts, particularly CD8+ T cell counts, were observed in patients with severe COVID-19 compared to those with mild COVID-19 from the onset of disease until day 16.

2. Severe COVID-19 patients have higher concentrations of IL-6, IL-10, IL-2 and IFN-g in their serum compared to mild cases, and I-6 and IL-10 showed sustained increase over the course of disease.

3. Neutrophil-to-CD8+ T cell ratios and neutrophil-to-lymphocyte ratios can serve as prognostic factors for disease severity.

Summary 

This study shows longitudinal changes in lymphocyte responses and cytokine profiles in 40 patients with severe or mild COVID-19. They show that severe cases had lower lymphocyte counts and higher neutrophil counts compared to mild cases. Lymphopenia in severe COVID patients is mainly related to significant decreases in (CD8+) T cell counts, which gradually recovers to comparable levels from the second a week after disease onset. Severe COVID-19 patients have higher concentration of IL-6, IL-10, IL-2 and IFN-g, compared to mild COVID-19 patients. Neutrophil-to-CD8+ T cell ratios and neutrophil-to-lymphocyte ratios were shown to be prognostic factors for disease severity. 

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19

This study demonstrates that patients with a more severe COVID-19 disease have lymphopenia, neutrophilia and an increase in pro-inflammatory cytokine levels compared to patients with mild COVID-19. They identify neutrophil-to-CD8+ T cell and neutrophil-to-lymphocyte ratio as potential prognostic factors`.

Study Type

Patient Case study

Strengths and limitations of the paper

Novelty: This study describes the kinetic changes in lymphocyte subsets and cytokine profiles and identifies neutrophil-to-CD8+ T cell ratios and neutrophil-to-lymphocyte ratios as prognostic factors for disease severity.

Standing in the field: It has been previously shown that lymphopenia and pro-inflammatory cytokine storm are involved in COVID-19 disease. This is the first study to explore the changes in lymphocyte count and pro-inflammatory cytokine number over the course of COVID-19 disease.

Appropriate statistics: Yes

Viral model used: SARS-CoV-2

Translatability: This study validates the use of neutrophil-to-CD8+ T cell ratio and neutrophil-to-lymphocyte ratio as prognostic markers for COVID-19 disease severity. This may be used to allow clinicians to identify infected patients at higher risk of severe COVID-19.

Main limitations: Small sample size. The cohort size (40 patients) is too small to draw broad conclusions from, particularly as the severe group is made up of only 13 patients, 3 of which are not included in the analysis.