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Authors: Adamo et al. 

Journal/ Pre-Print:bioXriv 

Key Words: Immunology/Immunity, Inflammation, Clinical 

Research Highlights 

  1. Lymphopenia is shown again to be a hallmark of severe COVID-19 infection. 

  1. T cell apoptosis and migration into inflamed tissues are identified as possible mechanisms driving peripheral T cell loss in sever COVID-19 infection. 

  1. Patients with severe COVID-19 show signs of IL-7-induced homeostatic proliferation of T cells 

  1. Expansion and recovery of poly-specific antiviral T cells suggests lymphopenia-induced T cell proliferation 

Summary  

The study provides detailed investigation of the peripheral T cell compartment in a cohort of patients with mild (n=28) or severe (n=38) COVID-19 and healthy controls (n=22). A decrease in peripheral T cell counts was associated with severe disease. T cell loss was associated with an increase in the percentages of apoptotic cells, suggesting Increased T cell apoptosis contribute to the lymphopeniaIn addition, increased level of ligands involved in CXCR3 signalling pathway along with a decreased CXCR3 expression on different T cell subsets suggest that T cell migration into inflamed tissue was another likely contributing factor to the observed lymphopenia in the peripheral compartment. Finally, using the different sampling time of the included patients with severe COVID-19 to as a pseudo-longitudinal time course, the authors also observe lymphopenia induced homeostatic proliferationdriving expansion of poly-specific T cells and indicating an improvement of T cell functionality over time. 

Impact for SARS-CoV2/COVID19 research efforts  

Understanding the immune response to SARS-CoV2/COVID19  

Study Type 

  • In vitro study 

  • Patient Case study 

Strengths and limitations of the paper 

Novelty: Findings reveal an important role of apoptosis and migration in driving T cell lymphopenia in severe COVID-19 

Standing in the field: Confirms lymphopenia to be a hallmark of severe COVID-19 

Appropriate statistics: Yes 

Viral model used:Blood from COVID-19 infected patients (confirmed by PCR) 

Translatability:The study highlights the potential of anti-inflammatory therapies, such as anti-TNF, in possibly preventing the observed extensive T cell loss in severe cases. 

Main limitations:  

  1. Patients were only sampled at a single time point during their symptomatic phase 

  1. As noted by the authors, next to IL-7, IL-15 is another important cytokine driving lymphopenia-induced homeostatic proliferation, whose role could not really be addressed in the current study 

  1. The authors did not investigate or focus on SARS-CoV-2-specific T cells 

  1. While the authors demonstrate an increase in T cell apoptosis, minimal evidence was provided for correlation between inflammation in severe cases and T cell apoptosis. That would help in explaining if the T cell apoptosis is driven by extensive inflammation or by another mechanism.