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Authors: Xiong et al.

Link to paper: https://www.ncbi.nlm.nih.gov/research/coronavirus/publication/32228226

Journal/ Pre-Print: Emerging Microbes & Infections

Key Words: bulk transcriptomics, BALF, PBMC, cytokines

Research Highlights 

1. Comparing BALF total RNA of 2 patients (no clinical characteristics) to 3 controls, cytokine genes such as for TGF-β, CXCL2, CCL8, etc were found upregulated.

2. Comparing PBMC total RNA of 3 patients (no clinical characteristics) to 3 controls, cytokine genes such as for IL10, CXCL10, C5, etc were found upregulated.

3. Viral gene expression was not found in PBMC total RNA.

Summary 

This study does not add much to current knowledge, but confirms possibility of a “cytokine storm” in Covid-19 patients. In bronchoalveolar lavage fluid of 2 patients, transcription of cytokines/chemokines and viral transcription/translation genes were upregulated. In PBMCs of 3 other patients, transcription of cytokines/chemokines and humoral immunity/complement activation genes were upregulated. Controls were taken from a public dataset, sampled from a different continent. Interestingly, IL-6 mRNA in PBMCs did not correlate with IL-6 protein in blood, although timepoint of sampling is unclear. There was high variation in gene expression values within the patient groups, which the authors did not explain.

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19 : this study could indicate which cytokines & chemokines could possibly be targeted, but the cohort size is too small for a firm conclusion. Also not described whether these were mild or severe cases.

Study Type 

· Bioinformatics study

· Patient Case study

Strengths and limitations of the paper

Novelty: No novel insights

Standing in the field: Confirms reports of a “cytokine storm”

Appropriate statistics: The analysis follows standard workflows developed for RNA-Seq data. But part of their conclusions are based on non-significant results and are hence much overstated.

Viral model used: SARS-CoV2

Translatability: Low; very small sample size and clinical status of patients not described. No validation or follow up of gene candidates is presented.

Main limitations: The paper does not describe whether these were mild or severe cases, nor the time point of sampling, nor the clinical outcome. Patients represent different age groups and it is not reported whether they present any comorbidities. This probably contributes to the observed variability in the results of the analysis. Cases were taken from a Wuhan hospital, whereas controls were healthy individuals from Switzerland processed and sequenced two years earlier.