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Authors:MacDonald et al. 

Journal/ Pre-Print:bioRxiv 

Tags: Bioinformatics, Drug discovery/Drug repurposing, Inflammation 

Research Highlights 

  1. Two macrophage subsets that drive synovitis in RA patients were found to be transcriptionally similar to two macrophage subsets expanded in the BALF of severe COVID-19 patients.  

  1. Similarly, a subset of lining resident macrophages which is associated with stable RA remission has a transcriptionally similar counterpart in the healthy alveolar tissue.  

  1. Using drugs which support the anti-inflammatory function of macrophages such as dexamethasone might be useful for COVID-19 treatment.  

Summary

Authors compared scRNA sequencing data of BALF myeloid cells of COVID-19 patients (Liao et al 2020) to myeloid cells of naïve, active RA or RA patients in remission (Alivernini et al 2020). They found that CD48highS100A12pos and CD48posSPP1pos macrophages, which drive synovitis, have a similar transcriptional profile to FCN1pos and FCN1posSPP1pos macrophages respectively, which are expanded in the BALF of severe COVID-19 patients. Similarly, TREM2pos lining macrophages, which are associated with stable RA remission, have a transcriptionally similar counterpart in the healthy alveolar tissue (FABP4pos). Repurposing of drugs that support anti-inflammatory functions of macrophages e.g. dexamethasone might be beneficial for COVID-19 patients.      

Impact for SARS-CoV2/COVID19 research efforts  

Understand the immune response to SARS-CoV2/COVID19  computationally predicted which macrophage subsets may contribute to COVID-19 pathology 

Treatment of SARS-CoV2/COVID19 positive individuals – rationale for repurposing of RA drug dexamethasone for COVID-19 treatment  

Study Type  

  • In silico study / bioinformatics study 

  • In vitro study  

Strengths and limitations of the paper 

Novelty: Showing the potential similarity between the role of macrophages in RA and COVID-19 with a rationale that drugs used for RA remission might be beneficially used for the COVID-19 treatment.   

Standing in the field:Not controversial. COVID-19 was shown to induce acute arthritis in patients who were in stable remission. Furthermore, a recovery trial of low dose dexamethasone (drug used for arthritis flares) preliminarily showed a decrease in deaths of hospitalised COVID-19 patients. 

Appropriate statistics:Appropriate 

Viral model used:SARS-CoV2 

Translatability:Rationale for repurposing of RA drugs for COVID-19 patients. However, dexamethasone is already being used to treat COVID-19. 

Main limitations: 1. In Liao et al 2020 (source scRNA seq dataset), BALF myeloid cells were isolated from healthy controls, mild and severe COVID-19 patients. Potentially also probing the recovered patients would be beneficial to be able to compare whether an increase in BALF FABP4pos macrophages is associated with the recovery, similarly to TREM2high macrophages in RA remission 

2. This study represents a computational comparison which requires further testing in vivo/in vitro systems to fully establish the functional role of macrophages in COVID-19. Also it is largely an observational study comparing two inflammatory diseases. It is perhaps not remarkable that similar subsets of inflammatory cells are detected in the two diseases.