Thread by @Gas_Craic

Is COVID-19 hyperinflammation, or a cytokine storm in a teacup? @DrPujaMehta1 's fab talk from #SOA21 today!

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

We now know some things work and some things don't.... in certain populations. #SOA21

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)?

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

So - what is cytokine storm? #SOA21 COVID meets all these definitions....

But cytokine storm syndromeS is really an umbrella term. COVID-19 sits under this umbrella. #SOA21

Similarly shown here - an overarching term. #SOA21

Why do some people get it? Bear in mind, this pathway shows DRUGGABLE therapeutic targets, that's why it's important #SOA21

Some key take-home messages about HLH. Likely requires a high level of vigilence #SOA21

Anakinra has been used to treat HLH: #SOA21

Turning OFF the cytokine storm. These are heavy immunomodulating drugs. #SOA21

So why not use anakinra in sepsis, if hyperinflammation DOUBLES mortality? #SOA21

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

Weak to Strong responses.... Lots of different treatment options to research... #SOA21

But still it was unlike other types of cytokine storm seen before. #SOA21 Clinically difference. LUNG thrombosis for eg.

MASSIVE validation cohort in the ISARIC-4C trial... Risk of mortality and deterioration in hospital. #SOA21

3 different criteria systems for COVID hyperinflammation. Unclear of their clinical utility.... #SOA21

Interesting profiles of biomarkers found in COVID-19 #SOA21

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

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

HOST factors are still important. Especially ones that incur a pre-existing pro-inflammatory state. #SOA21

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.

What future things could guide treatment? #SOA21 suPAR could be an earlier predictive biomarker!

Of course there are directions in NON-COVID (what's that?) immune profiling too ;) #SOA21

DO WE HAVE A NEW HYPERINFLAMMATORY DISORDER?? Hmmm.... unclear.... #SOA21 How even will variants/vaccines affect hyperinflammation?

A final word as a testimony to cross-specialty working. #SOA21

@DrPujaMehta1 - what a wonderful speaker with such a vast and interesting research area! Thanks for speaking today! #SOA21