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Kenneth Baillie Profile picture
@kennethbaillie
Oct 17, 2019 • 5 tweets • 4 min read • Read on X
I'll be talking about how genomics might offer clues to design new treatments for sepsis at #WCIC19. Ultimately this needs global effort, led by local clinicians: download our free, open-source research protocol here: genomicc.org
This work is generously funded by @stopsepsisnow , @wellcometrust and @icsupdates
@stopsepsisnow @wellcometrust @icsupdates This reference summarises the main approach we're suggesting. Patients don't fall into mutually-exclusive categories. We need to move away from phenotypes and focus on identifying treatable traits research.ed.ac.uk/portal/files/3…
@stopsepsisnow @wellcometrust @icsupdates And, for those who like this sort of thing, the effective shunt calculator is here baillielab.net/es
@stopsepsisnow @wellcometrust @icsupdates Finally, Lucile Neyton's excellent work, providing the first evidence that critical illness sub-phenotypes are generalisable across different syndromes (pancreatitis and ARDS in this case) is free and open access here: biorxiv.org/content/10.110…

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More from @kennethbaillie

Kenneth Baillie Profile picture
Mar 30, 2023
Am delighted to say we've just published two papers in Nature arising from the ISARIC4C study. We used our pre-approved "sleeping" protocol to investigate the unexplained outbreak of hepatitis in kids last year. A thread...
This is the best example I've seen of academic researchers working hand-in-glove with national public health agencies to tackle a new threat. Because we had the ISARIC4C (isaric4c.net) study infrastructure in place before the outbreak...
... we were able to find strong evidence for the underlying cause of a completely new disease, within a few months of the first case being reported.
Read 17 tweets
Kenneth Baillie Profile picture
Oct 27, 2021
I've been thinking about this and the responses. There are many complex problems in the NHS but I can give you some simple, important facts that I know to be true, from my own observations. 1/n
When a healthcare system fails, increasing numbers of people suffer and die needlessly. That's all. If you aren't a patient or staff, you don't see it. But this is happening, now, all over the UK. 2/n
The main problem is Covid: more Covid means fewer nurses and doctors (they get it too), and more patients. We have too many patients, and not enough staff. 3/n
Read 7 tweets
Kenneth Baillie Profile picture
Dec 11, 2020
Our discovery of 4 human genetic variants underlying life-threatening illness in Covid-19 is past peer review and has just been published: nature.com/articles/s4158…

Here's what we found: (1/n)
There are 5 positions on the genome that are strongly associated with critical illness (i.e. getting so sick that you need intensive care) in our study:
The nearest genes are called LZTFL1, OAS1, DPP9, TYK2, and IFNAR2.

This is where it starts to get interesting. For years we've been saying that we can find drug targets in critical care using genetics. (e.g. science.sciencemag.org/content/344/61…)
Read 24 tweets
Kenneth Baillie Profile picture
Sep 25, 2020
We have found some robust new discoveries about Covid-19 in GenOMICC, which have potential therapeutic relevance. Readers outside of the genomics community will want to wait for peer review before acting on these findings. Preprint here for specialists:
medrxiv.org/content/10.110…
By looking across the entire genome in critically ill patients we open up the possibility of discovering something completely new. We have found and replicated new, robust and potentially therapeutically-relevant genetic associations. Image
Crucially - no-one should change their clinical practice until large-scale clinical trials have confirmed or refuted these predictions.
Read 5 tweets
Kenneth Baillie Profile picture
Sep 1, 2020
Which host genes play a role in viral replication/host response to SARS-CoV-2? We're systematically reviewing and meta-analysing the literature (12,000 papers so far!) to find out. Current top hit is PPIA, a gene which encodes cyclophilin A. All results: baillielab.net/covid
Modern biological research often generates lists of genes implicated in the process being studied - the trouble is, it can be very difficult to assess the quality and relevance of these results.
Over the past few years we've developed an algorithm: meta-analysis by information content (MAIC), which assigns a weighting to each gene in each study, quantifying the supporting evidence from that source. We first reported it here: nature.com/articles/s4146…
Read 7 tweets
Kenneth Baillie Profile picture
Jul 5, 2020
Important new COVID data. Two things have recently altered my perception of the mechanisms of critical illness in COVID-19. Together, dexamethasone and this autopsy series (@davidadorward, Chris Lucas, @clarkdrussell @COVID_ICECAP) change everything 1/n
medrxiv.org/content/10.110…
This shows that tolerance - the presence of a pathogen in the absence of tissue damage - is common in fatal COVID in humans. But it is tissue-specific. Some tissues have virus but no inflammation/damage; some, such as lung, have inflammation damage but little or no virus 2/n
Even in the lungs in some cases, there can be lots of virus without damage to the tissue. 3/n
Read 6 tweets

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