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COVID is not like flu
Also it is *not* a sepsis
COVID is no longer a syndrome
Late, immune-mediated hurt (primarily vessel) is the main driver of organ dysfunction. Corticoids work
signed, someone who was deemed "a sepsis nerd" during residency & later finished a PhD on sepsis
Also it is *not* a sepsis
COVID is no longer a syndrome
Late, immune-mediated hurt (primarily vessel) is the main driver of organ dysfunction. Corticoids work
signed, someone who was deemed "a sepsis nerd" during residency & later finished a PhD on sepsis
If anything, it looks more like a systemic lupus flare than any sepsis we've seen before
I don't think COVID ARDS benefits from corticoids...
I rather think that COVID itself benefits from corticoids, which is a slightly different point of view.
Don't treat ARDS with corticosteroids. Treat COVID
I rather think that COVID itself benefits from corticoids, which is a slightly different point of view.
Don't treat ARDS with corticosteroids. Treat COVID
This study came in early Feb 2020, from a group we collaborated with for years
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(19)30417-5/fulltext
It wasn't enough evidence for us to use cortics in COVID
At least in the beginning
We were very reluctant to use any cortics in COVID ARDS
Afraid of impairing antiviral response
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(19)30417-5/fulltext
It wasn't enough evidence for us to use cortics in COVID
At least in the beginning
We were very reluctant to use any cortics in COVID ARDS
Afraid of impairing antiviral response
Back then, we were told COVID was primarily a pneumonia, very much like severe flu
Then, together with other physician peers, saw that this wasn't the case
Patients had been at home, with viral infection symptoms. After about 10 days, their condition worsened and were admitted
Then, together with other physician peers, saw that this wasn't the case
Patients had been at home, with viral infection symptoms. After about 10 days, their condition worsened and were admitted
Almost all of them needed oxygen from the beginning.
In blood, they showed signs of early DIC, and incipient macrophage activation syndrome.
In intubated: oxygen saturation very low & very soft lungs.
If alveoli were clogged, compliance should be lower, like any other ARDS!
In blood, they showed signs of early DIC, and incipient macrophage activation syndrome.
In intubated: oxygen saturation very low & very soft lungs.
If alveoli were clogged, compliance should be lower, like any other ARDS!
We know DIC can happen after viral infections since 1967
Most likely cause: endotheliopathy initiated by viral invasion (due to ACE-receptors in endothelium, efficiently binded by the SARS-CoV-2 spike proteins)
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/573720
Most likely cause: endotheliopathy initiated by viral invasion (due to ACE-receptors in endothelium, efficiently binded by the SARS-CoV-2 spike proteins)
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/573720
Uncontrolled endothelial damage+activation resembled microangiopathy, actually seen in autopsies. Autopsy series gave us further clues
Continuous lymphocite activation leads to signalling exhaustion, apoptosis (lymphopenia) and in some cases to macrophage activation
Continuous lymphocite activation leads to signalling exhaustion, apoptosis (lymphopenia) and in some cases to macrophage activation
In this probable scenario of impaired cell response, macrophage activation is thought to be the main driver of the cytokine storms, as the main IL-6 producers
Fatty tissue may amplify macrophage response, as fats can be used to make inflammatory mediators https://pubmed.ncbi.nlm.nih.gov/28641779
Fatty tissue may amplify macrophage response, as fats can be used to make inflammatory mediators https://pubmed.ncbi.nlm.nih.gov/28641779
Microangiopathy was overrepresented in lungs. Probably, due to a higher concentration in ACE-R, present in endothelium and epithelium.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1287568/
But also could be present in other organs. Even skin & fingertips
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1287568/
But also could be present in other organs. Even skin & fingertips
Upon reviewing this plethora of findings in our patients, with peers of several specialities, it began to become clear that there was ground for immunosuppresant treatments
Our colleagues began administering them in rapidly deteriorating patients
Our colleagues began administering them in rapidly deteriorating patients
Those patients were, undoubtely going to need ICU care
Some of them improved but still ended up in ICU
However, others improved so rapidly that they avoided ICU care at all
And it seemed the response to corticoids was quite consistent in new patients
Unlike under HCQ treatment
Some of them improved but still ended up in ICU
However, others improved so rapidly that they avoided ICU care at all
And it seemed the response to corticoids was quite consistent in new patients
Unlike under HCQ treatment
More aggresive immunosuppresants (anti-interleucins like tocilizumab, anakinra) were given less frequently.
Based on strict criteria, due to their potential for severe adverse events.
Based on strict criteria, due to their potential for severe adverse events.
So we 'observed' immunosuppresants were likely to be effective.
Not based on the ARDS-net study, but on discussing the COVID distinct features, linking to already known syndromes
What was confusing, was calling this 'a flu'
Not based on the ARDS-net study, but on discussing the COVID distinct features, linking to already known syndromes
What was confusing, was calling this 'a flu'
In fact, shares some immunological features of severe dengue disease & ebola disease (although those viruses are themselves more pathogenic than SARS-CoV-2)
Controlling viral virulence (replication & IFN inhibition) while controlling lethal host response will be key in COVID-19
Controlling viral virulence (replication & IFN inhibition) while controlling lethal host response will be key in COVID-19
