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#singlecell #COVID19 paper alertThis one has lots of clues for our understanding of #COVID19 and heavily implicates mononuclear phagocytes as central to severe pathology.
A thread....
https://www.biorxiv.org/content/10.1101/2020.04.08.029769v1
They sampled #PBMC from severe and recovery stage #COVID19 and integrated data with reference healthy #PBMC
Fairly standard cell type annotation.
Recovery stage samples are after Tocilizumab - anti-IL6R monoclonal Ab
Fairly standard cell type annotation.
Recovery stage samples are after Tocilizumab - anti-IL6R monoclonal Ab
Fairly standard cell type annotation.
This bit is easy for PBMC nowadays and can be semi automated...
Cluster 13 are clearly T-mono doublets. Maybe these are physiological? Evidence of physical interaction/crosstalk? 
This bit is easy for PBMC nowadays and can be semi automated...
Cluster 13 are clearly T-mono doublets. Maybe these are physiological? Evidence of physical interaction/crosstalk?
there is a monocyte cluster specific enriched in severe #COVID19 and receding during recovery/anti-IL6R...Expressing LOADS of cytokines & chemokines #Inflammasome gene upregulation (Il1B, NRLP3)Severe #COVID19 monocytes express 
IL6 
Severe #COVID19 monocytes also express C1QA - B- C which suggests to me differentiation towards a macrophage phenotype. 
Are they on their way to becoming inflammatory tissue macrophages in the lung?
Another #COVID19 #singlecell @medrxivpreprint on patients shows https://www.medrxiv.org/content/10.1101/2020.02.23.20026690v1.full.pdf inflammatory monocyte/macrophage population in bronchoalveolar lavage fluid
Does the severe-mono population in the blood look like any of these BAL populations?
Back to the tocilizumab study...
They also see prominent plasma cells which recede during recovery, and are rare in health.
There are some proliferating and effector CD8 T cells expressing PRDM1.
They also see prominent plasma cells which recede during recovery, and are rare in health.There are some proliferating and effector CD8 T cells expressing PRDM1.
Authors looked at putative interactions using CellPhoneDB - 
tool developed by @teichlab @mirjana_e @roserventotormo
Severe stage enriched for mono->lymphocyte signalling
Some IL6-IL6R signalling 
after tocilizumab
severe stage monos signal -> plasma cells ++
tool developed by @teichlab @mirjana_e @roserventotormo Severe stage enriched for mono->lymphocyte signallingSome IL6-IL6R signalling after tocilizumabsevere stage monos signal -> plasma cells ++
Overall model is that in severe #COVID19, monocytes are v activated and signal to lymphocytes incl plasma cells to orchestrate the phenotype...
Tentative implications:
Need to break myeloid/innate activation - that seems proximal.
IL6 blockade seems well motivated given these data
Inflammasome blockade also worth trying
Need to break myeloid/innate activation - that seems proximal.IL6 blockade seems well motivated given these dataInflammasome blockade also worth trying
