Is COVID-19 hyperinflammation, or a cytokine storm in a teacup? @DrPujaMehta1 's fab talk from #SOA21 today! Image
Main Q = "Hyperinflation contributing to worse outcomes for some patients with COVID-19" - clinical similarities to sHLH seen. Viruses are the most common trigger of sHLH. Early reports from China suggested cytokine profile was similar to sHLH in terms of COVID severity. #SOA21 Image
We now know some things work and some things don't.... in certain populations. #SOA21 Image
But it forced us to look at, "what is a cytokine storm?" IL-6 is actually quite low in COVID. Did our obsession with cytokine storm distract us from antivirals and vaccines (at the time)? Image
Fast track review looked at IL-6 in COVID vs other critical illnesses. SO much higher in other critical illnesses. (ONLY IL-6 was looked at, systemically). #SOA21 Image
So - what is cytokine storm? #SOA21 COVID meets all these definitions.... Image
But cytokine storm syndromeS is really an umbrella term. COVID-19 sits under this umbrella. #SOA21 Image
Similarly shown here - an overarching term. #SOA21 Image
Why do some people get it? Bear in mind, this pathway shows DRUGGABLE therapeutic targets, that's why it's important #SOA21 Image
Some key take-home messages about HLH. Likely requires a high level of vigilence #SOA21 ImageImage
Anakinra has been used to treat HLH: #SOA21 ImageImage
Turning OFF the cytokine storm. These are heavy immunomodulating drugs. #SOA21 ImageImage
So why not use anakinra in sepsis, if hyperinflammation DOUBLES mortality? #SOA21 Image
How does all this relate to COVID-19? Well... viraemic phase followed by host dysregulation. This figure shows well the reason why drug timings are important. (ie: why antivirals might be good at X time, and immune modulators at another). This is not every patient. #SOA21 Image
Weak to Strong responses.... Lots of different treatment options to research... #SOA21 ImageImage
But still it was unlike other types of cytokine storm seen before. #SOA21 Clinically difference. LUNG thrombosis for eg. Image
MASSIVE validation cohort in the ISARIC-4C trial... Risk of mortality and deterioration in hospital. #SOA21 Image
3 different criteria systems for COVID hyperinflammation. Unclear of their clinical utility.... #SOA21 Image
Interesting profiles of biomarkers found in COVID-19 #SOA21 Image
So - if we give drugs to dampen immune response, is this advantageous to patients? Well - context is everything and so is timing of drugs. There is a window of opportunity. #SOA21 Image
Could we look at GM-CSF as a target? It's associated with endothelial injury and thrombosis. High GM-CSF levels were not found in fatal FLU, but were found in fatal COVID. #SOA21 ImageImageImage
HOST factors are still important. Especially ones that incur a pre-existing pro-inflammatory state. #SOA21 Image
So is it a cytokine storm.... sort of....? Maybe....? #SOA21 Why did the removal of cytokines via CytoSorb have worse outcomes on ECMO? Confounded? It's likely to be a mixture of a lot of things. Image
What future things could guide treatment? #SOA21 suPAR could be an earlier predictive biomarker! ImageImage
Of course there are directions in NON-COVID (what's that?) immune profiling too ;) #SOA21 Image
DO WE HAVE A NEW HYPERINFLAMMATORY DISORDER?? Hmmm.... unclear.... #SOA21 How even will variants/vaccines affect hyperinflammation? ImageImage
A final word as a testimony to cross-specialty working. #SOA21 Image
@DrPujaMehta1 - what a wonderful speaker with such a vast and interesting research area! Thanks for speaking today! #SOA21

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More from @Gas_Craic

8 Dec
What were the most impactful non-COVID papers over the past 2 years? Let's delve in and take a look. #SOA21 Image
Finally an opportunity to not talk about COVID! #SOA21 ImageImageImage
TOMAHAWK - immediate vs delayed/selective angio. 3 years to conduct the trial in 31 ICUs. 554 patients. 'Worse' survival in immediate angiograph? Not SS, but close... #SOA21 ImageImageImageImage
Read 27 tweets
8 Dec
We've looked at bats for a long time.... #SOA21 They have strong interferon responses, but not strong inflammation.... Image
So what happens instead? #SOA21 They will tolerate high levels of viraemia with little symptoms. Bats are old... 65million years ago - they appeared at the end of the dinosaurs! They are far longer lived that other mammals. Senescence is late - more towards end of life. Image
Read 14 tweets
7 Dec
Organophosphate poisoning, toxicology, dengue, snake bites and malaria.... sure what could go wrong? #SOA21 @ICS_updates Drs. Chacko, Yacoub, Bhaumik and Dondorp tell us more.... 🧵👇😘 Image
Let's go to India - Tamil Nadu. ImageImage
I'd advise anyone not overly family with Organophosphates to start here: ncbi.nlm.nih.gov/books/NBK49986… #SOA21
Read 43 tweets
7 Dec
Biomarker guided abx treatments in sepsis. We catch up with Drs/Profs: Paul Dark, Stacy Todd, Enitan Carrol, Jonathan Sandoe and Matthew Stevenson on this large area of research @ICS_updates #SOA21
So, do biomarkers have any utility in guiding abx use in sepsis? We can measure, usually, these ones fairly easily: #SOA21
In around 2014, commissioned review in PCT. Seemed to suggest a shorter duration in abx use when PCT used.... tenuous data though. #SOA21 Low quality. Little evidence from UK... how does this fit into NHS practice in the realms of stewardship?
Read 13 tweets
7 Dec
@iceman_ex, myself and @dr_mattmorgan talk about how to keep yourself intellectually safe on Social Media at #SOA21 (full talk at soa.ics.ac.uk)

A thread 🧵👇
There's been a lot that's gone on over the past few years that's exposed the well known 'darker' side of social media. Traditional paradigms of knowledge dissemination have changed (if not disappeared). Much higher tech-savy population. #SOA21
This has democratised the discussion space to an extent. It allows for *anybody* (lit. anybody) to get involved. #SOA21
Read 17 tweets
6 Dec
What have we learned during COVID? Prof Tony Gordon takes us through a whirlwind tour of COVID-19 research.... #SOA21 Image
Scientists AND politicians in the spotlight during COVID. Very different approaches between the two groups.#SOA21 Image
First reports and articles with hundreds of patients.... moving on to thousands of patients. #SOA21 ImageImage
Read 21 tweets

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