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Authors: Grant et al 

Journal/ Pre-Print:bioRxiv 

TagsBioinformatics, Clinical, Immunology/Immunity, Inflammation 

Research Highlights 

  1. Multiparameter FACS profiling of bronchoalveolar lavage (BAL) from severe COVID-19 patients to pneumonia and other intubated patients 

  1. Identification of positive feedback loop between alveolar macrophages and T cells in SARS-CoV-2 

  1. Alveolar macrophages harbouring the virus may be a non-specific reservoir for SARS-CoV-2 

Summary 

Grant et al aimed to profile the BAL of 86 severe intubated COVID-19 patients and compare them to profiles of 252 patients being intubated for pneumonia from other respiratory viruses or bacteria and intubated patients without pneumonia. They performed multicolour flow cytometry, bulk transcriptomic profiling of alveolar macrophages and scRNA-seq. Their findings suggest a model where alveolar macrophages can harbour SARS-CoV-2 and form self-sustaining circuits with T cells that drive alveolar inflammation. SARS-CoV-2 results in the recruitment of T cells and monocyte, rather than neutrophils in the lung. The composition of immune cells in SARS-CoV-2 is relatively stable and slowly unfolds over time, leading to a loss of tissue-resident macrophages and compensating recruitment of monocytes.  

Impact for SARS-CoV2/COVID19 research efforts  

Understand the immune response to SARS-CoV2/COVID19: identification of self-sustaining circuits driving alveolar inflammation  

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19: Comparison of intubated SARS-CoV-2 patients with intubated patients with pneumonia or for other reasons 

Study Type  

  • In silico study / bioinformatics study 

  • Clinical Cohort study (e.g. drug trials) 

Strengths and limitations of the paper 

Novelty: earliest sampling of BAL with COVID-19 pneumonia to characterise early events & comparison to other types of pneumonia and mechanical ventilation 

Standing in the field:IL-6 could not be detected, neutrophilia neither nor elevated type I interferon responses  

Appropriate statistics: statistical tests clearly stated in figure legends and methods, normal distribution was assumed for all tests 

Viral model used:original SARS-CoV-2 (US) 

Translatability:Model that explains slow progression, epidemiology (mainly affecting elderly individuals) and localised areas of infection 

Main limitations: BAL fluid collected within 48h of intubation, so they speculate about stage and severity of disease (but call it early events that lead to pneumonia)study seems thorough but fails to replicate some findings from other studies (see standing in the field), it would have been interesting to assess antibodies in these BAL fluids