https://abs.twimg.com/emoji/v2/... draggable="false" alt="🚨" title="Police cars revolving light" aria-label="Emoji: Police cars revolving light"> #singlecell #COVID19 paper alerthttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🚨" title="Police cars revolving light" aria-label="Emoji: Police cars revolving light">
This 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">https://www.biorxiv.org/content/1...

They sampled #PBMC from severe and recovery stage #COVID19 and integrated data with reference healthy #PBMC
Fairly standard cell type annotation.
https://abs.twimg.com/emoji/v2/... draggable="false" alt="🤩" title="Star-struck" aria-label="Emoji: Star-struck">Recovery stage samples are after Tocilizumab - anti-IL6R monoclonal Abhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🤩" title="Star-struck" aria-label="Emoji: Star-struck">

Fairly standard cell type annotation.
This bit is easy for PBMC nowadays and can be semi automated... https://abs.twimg.com/emoji/v2/... draggable="false" alt="🤨" title="Face with raised eyebrow" aria-label="Emoji: Face with raised eyebrow">

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">Cluster 13 are clearly T-mono doublets. Maybe these are physiological? Evidence of physical interaction/crosstalk? https://abs.twimg.com/emoji/v2/... draggable="false" alt="🤷‍♂️" title="Man shrugging" aria-label="Emoji: Man shrugging">

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">there is a monocyte cluster specific enriched in severe #COVID19 and receding during recovery/anti-IL6R...
https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">Expressing LOADS of cytokines & chemokines
https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol"> #Inflammasome gene upregulation (Il1B, NRLP3)
https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">Severe #COVID19 monocytes express https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Upwards arrow" aria-label="Emoji: Upwards arrow">IL6 https://abs.twimg.com/emoji/v2/... draggable="false" alt="🤒" title="Face with thermometer" aria-label="Emoji: Face with thermometer">

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">Severe #COVID19 monocytes also express C1QA - B- C which suggests to me differentiation towards a macrophage phenotype.
https://abs.twimg.com/emoji/v2/... draggable="false" alt="⁉️" title="Exclamation question mark" aria-label="Emoji: Exclamation question mark">Are they on their way to becoming inflammatory tissue macrophages in the lung?

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">Another #COVID19 #singlecell @medrxivpreprint on patients shows
https://www.medrxiv.org/content/10.1101/2020.02.23.20026690v1.full.pdf">https://www.medrxiv.org/content/1... inflammatory monocyte/macrophage population in bronchoalveolar lavage fluid

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⁉️" title="Exclamation question mark" aria-label="Emoji: Exclamation question mark">Does the severe-mono population in the blood look like any of these BAL populations?

Back to the tocilizumab study...

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">They also see prominent plasma cells which recede during recovery, and are rare in health.
https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">There are some proliferating and effector CD8 T cells expressing PRDM1.

Authors looked at putative interactions using CellPhoneDB - https://abs.twimg.com/emoji/v2/... draggable="false" alt="💪" title="Flexed biceps" aria-label="Emoji: Flexed biceps">tool developed by @teichlab @mirjana_e @roserventotormo https://abs.twimg.com/emoji/v2/... draggable="false" alt="💪" title="Flexed biceps" aria-label="Emoji: Flexed biceps">

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">Severe stage enriched for mono->lymphocyte signalling
https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">Some IL6-IL6R signalling https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Downwards arrow" aria-label="Emoji: Downwards arrow"> after tocilizumab
https://abs.twimg.com/emoji/v2/... draggable="false" alt="💥" title="Collision symbol" aria-label="Emoji: Collision symbol">severe 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:
https://abs.twimg.com/emoji/v2/... draggable="false" alt="🚫" title="No entry sign" aria-label="Emoji: No entry sign">Need to break myeloid/innate activation - that seems proximal.
https://abs.twimg.com/emoji/v2/... draggable="false" alt="💊" title="Pill" aria-label="Emoji: Pill">IL6 blockade seems well motivated given these data
https://abs.twimg.com/emoji/v2/... draggable="false" alt="💊" title="Pill" aria-label="Emoji: Pill">Inflammasome blockade also worth trying