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Authors: Zhuo Zhou et al.

Link to paper:

Journal/ Pre-Print: Cell host & microbe

NB: supplemental information not available at time of reviewing

Tags: Cell Biology, Immunology/Immunity, Inflammation, Transcriptomics

Research Highlights

1. Metatranscriptomic of bronchoalveolar lavage fluid (BALF) from COVID-19 cases shows increased innate immune response signature

2. Interferon stimulated genes (ISGs) are increased in COVID-19 BALF, but not interferons themselves.

3. Cytokines (especially chemokines) are increased in COVID-19 BALF


This is a descriptive metatrascriptomic study of BALF from 8 patients (at different days since onset, with variable viral loads) compared with BALF from 20 healthy control and 146 community-acquired pneumonia cases (collected 2-6 years earlier in another centre). RNAseq data of COVID-19 vs healthy show that the highest differentially expressed genes are for proinflammatory cytokines and chemokines (with chemokines for neutrophil migration being the prominent ones) and interferon-stimulated genes (ISGs). Deriving protein-protein interaction networks also shows upregulation of ISGs, chemokines and ribosome pathways. Cell composition of BALF shows elevated neutrophils and neutrophils to lymphocyte ratio in COVID-19 patients.

Impact for SARS-CoV2/COVID19 research efforts

Understand the immune response to SARS-CoV2/COVID19

Study Type

· Clinical Cohort study – ex vivo BALF RNA-seq (n=8)

Strengths and limitations of the paper

Novelty: The patient data for this paper come from BALF instead of peripheral blood like in many other previous papers. Also, the paper includes not only data of healthy controls and Covid-19 patients but also of bacterial and viral pneumonia patients.

Standing in the field: Supports the reported cytokine storm and elevated neutrophil count in patients that has previously been reported, locally in the lungs. There are conflicting reports regarding the activation of Type I IFN pathways in COVID-19 patients

Appropriate statistics: Methods seem correct, but in most plots they only compare the different patient groups to HC. It would have been informative to directly compare the Covid-19 patients to patients with other viral pneumonia.

Viral model used: NA – ex vivo analysis of human blood

Translatability: The sample group is small but does warrant careful reappraisal of treating Covid-19 patients with exogenous interferons.

Main limitations:

· Supplemental information not yet available

· Only 8 patients, not matched for DSO or disease severity, not clear if they had underlying conditions.

· Healthy control BALF as collected and extracted several years before and in another centre.

· The community-acquired pneumonia cohort is about 20 times bigger than the COVID-19 one and collected and extracted several years before and in another centre.

· The paper overstates some of the results, especially when trying to correlate phenotypes with disease severity or DSO, not enough patients per group.

· No confirmation of RNA results on a protein level.