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Authors: Li, Hui et al.

Link to paper: https://www.sciencedirect.com/science/article/pii/S0163445320302073?via%3Dihub

Journal/ Pre-Print: Apr 24, 2020. Journal of Infectiology, PMID: 32325129

Key Words: 2019 coronavirus pneumonia in children, lymphocyte subsets, serum cytokines

Tags: Immunology/Immunity; Clinical

Research Highlights

1. Higher frequencies and counts of peripheral CD8 T cells reported in children experiencing acute Covid-19 vs respiratory syncytial virus (RSV) pneumonia

2. IL-6 levels concomitantly increased with CRP and decrease after antibiotic therapy

Summary 

Li et al analyse the phenotype of lymphocyte subsets and serum cytokine levels in peripheral blood samples obtained from children with Covid-19 vs RSV pneumonia. The authors report increased frequencies and absolute numbers of CD8 T cells and reduced IL-10 levels in Covid-19 vs RSV patients. This data suggests a robust CD8 T cell response alongside limited IL-10 production may contribute to the mild pneumonia phenotype seen in SARS-CoV-2 infected children. However, further studies utilising healthy controls and comparisons to adult cases of Covid-19 are required.

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19

Phenotyping of lymphocyte subsets and serum cytokine levels in peripheral blood samples obtained from children with Covid-19 vs RSV pneumonia. Aim is to determine what immune parameters may contribute to the mild pneumonia phenotype of SARS-CoV2 infection in children.

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19

Authors report clinical manifestations, including incidence of dyspnea, results of chest CT scans, CRP levels etc., in children suffering with Covid-19 vs RSV pneumonia.

Study Type

· Patient case study

Retrospective study with COVID-19 vs RSV pneumonia in children admitted between 10 December 2019 and 22 February 2020 to Wuhan’s children hospital

Strengths and limitations of the paper

Novelty: Suggested implication for CD8 T cells/restricted IL-10 production in the mild pneumonia phenotype of Covid-19 seen in children. Requires confirmation through comparison with healthy controls and adult Covid-19 cases.

Standing in the field:

Reported increases of CD8+ T cell levels in the acute phase of Covid-19 pneumonia is in contrast to the current literature that reports leukopenia in children and adults in COVID-19 disease (e.g. https://www.nejm.org/doi/full/10.1056/NEJMc2003717). However, reduced levels of CD8 T cells (along with other immune parameters) have been shown in severe vs mild/moderate Covid-19 cases in adults (e.g. https://www.ncbi.nlm.nih.gov/pubmed/32344320 and https://www.ncbi.nlm.nih.gov/pubmed/32324595), suggesting CD8 counts may play some role in disease severity.

Confirms existing literature on high IL-6 levels and highlight importance of concomitant infections during COVID-19 which might affect different cell subtypes.

Appropriate statistics: Yes 

Viral model used: patient study confirmed via RT-qPCR

Translatability: The data presented do not have any immediate translational implications.

Main limitations:

· No healthy controls included therefore reference to normality not possible

· Small patient cohort, n = 56, of which n = 40 and n = 16 for the Covid-19 and RSV pneumonia groups, respectively

· Subjects not stratified according to severity due to low numbers (n=3 and 2 for Covid-19 and RSV pneumonia groups, respectively)

· Severity of pneumonia solely classified as entry to ICU

· Retrospective study

· Treatment start point clarified for I/V glucocorticoids only. Otherwise samples only clarified as collected 3 days post hospital admission

· Difference in age between the two groups, which may limit the conclusions since age is an extremely important variable in lymphocyte subset distributions in children.

· SARS-CoV-2 viral titre not monitored

· Missing gate strategy for Flow Cytometry

· Study limited to lymphocytes, no consideration of potential differences in myeloid cells