A possible role of immunopathogenesis in COVID-19 progression

Authors: Anft et al.

Link to paper: https://www.medrxiv.org/content/10.1101/2020.04.28.20083089v1.full.pdf

Journal/ Pre-Print: Medrxiv

Tags: Immunology/Immunity, Clinical

Research Highlights

1. Frequencies of differentiated and activated lymphocytes are decreased in patients with critically severe COVID-19 compared to a moderate group.

2. Increased frequency of activated cytotoxic (CD8+) T lymphocytes is associated with clinical improvement in follow-up.

3. Increased frequency of cytokine producing S-protein-reactive T cells in patients with critical COVID-19 compared to moderate disease.

Summary 

In this study, the authors recruited 53 COVID-19 patients and characterised the lymphocyte compartment clustered by clinical severity: moderate, severe and critical (admission to ICU). The overall proportion of CD8+ and CD4+ T lymphocytes with an activated or memory phenotype were decreased, whilst the frequency of cytokine-producing S-protein-reactive T cells was increased in the critical group compared to moderate and severe patients. The increase in viral antigen-specific T cells is at odds with the systemic reduction in T cell activation markers, suggesting a dysfunctional immune response. Of note, the activation and differentiation profile of viral antigen-specific T cells is not explored here. Increased lymphocyte activation was associated with improved clinical outcomes in severe cases, despite continuing lymphopenia.

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

Strengths and limitations of the paper

Novelty: In critical (ICU) patients, cytokine producing SARS-CoV-2-specific T cell frequencies are increased despite a loss in overall lymphocyte activation and differentiation markers in circulation.

Standing in the field: The authors have good standing in the field of immunology an dviral infection.

Appropriate statistics: No. Not statedclear which statistical tests were used and no adjustment fo, although states that no tests for multiple comparisons was carried outere used. 

Viral model used: Patients (from Germany) confirmed positive for SARS-CoV-2 by PCR. For measuring viral antigen-specificity, used SARS-CoV-2 PepTivator peptide pool (Miltenyi Biotech) for surface proteins.

Translatability:No obvious translational benefit. If anything, the study suggests that vaccination approaches may not be successful as the most severely affected patients exhibited the most robust anti-viral responses. [Is there a translational potential? How close is it to bedside?]

Main limitations: 53 patients: 21 moderate, 18 severe and 14 critical, hence insufficient numbers to draw definitive conclusions.

Would benefit from inclusion of healthy controls as a reference for activation and differentiation state of lymphocytes.

The viral specificity of lymphocytes is could be validated using broader peptide pools.

Missing data on the activation and differentiation phenotype of viral antigen-specific cells.