Cytokine storm patients......

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Marcus Aurelius
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1:04p, 4/2/20
AG
Witnessing another one. Symptom day 10 sudden huge spike in ferritin, CRP, LFTs and neutrophil/lymphocyte ratio. Chest x-ray ARDS exploding. Max vent, proned. New onset renal failure and shock. Depressing. Nothing to do but watch the inevitable play out. Steroids? Can't get compassionate IL-6 inhibitors now.
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Pasquale Liucci
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In reply to Marcus Aurelius • 1:06p, 4/2/20
AG
I know you can't share too much but can you give us an indication of demographic category?

Young / old?
Preexisting condition or no?
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BadMoonRisin
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1:10p, 4/2/20
goodAg80
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In reply to Marcus Aurelius • 1:11p, 4/2/20
AG
Marcus Aurelius said:
Witnessing another one. Symptom day 10 sudden huge spike in ferritin, CRP, LFTs and neutrophil/lymphocyte ratio. Chest x-ray ARDS exploding. Max vent, proned. New onset renal failure and shock. Depressing. Nothing to do but watch the inevitable play out. Steroids? Can't get compassionate IL-6 inhibitors now.
Why not?
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Pasquale Liucci
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In reply to Marcus Aurelius • 1:12p, 4/2/20
AG
And by "can't get" do you mean shortage of or legally you can't prescribe it off label?
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DadofanAngel03
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In reply to Marcus Aurelius • 1:15p, 4/2/20
AG
Has there been much info from the Sobi Gamifant study? I can't find any update. Gamifant (emapalumab) helps with calming the cytokine storm with HLH patients.

https://www.sobi.com/en/press-releases/sobi-initiate-clinical-study-evaluate-whether-anakinra-and-emapalumab-may-relieve
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Marcus Aurelius
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1:19p, 4/2/20
AG
Early elderly. HTN. We have reached out with no luck for IL-6 inhibitors.
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McInnis 03
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In reply to Marcus Aurelius • 1:23p, 4/2/20
AG
This is ludicrous. We've known about the ability and need of the il6 drugs since South Korea started spreading the word weeks ago...

I'm sorry
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dermdoc
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In reply to Marcus Aurelius • 1:31p, 4/2/20
AG
Marcus Aurelius said:
Early elderly. HTN. We have reached out with no luck for IL-6 inhibitors.
If the patient was me or a loved one and IL 6 was not available, I personally would want my doc to bolus me with steroids.

I am curious also about the use of anti tumor necrosis factor meds like Enbrel or Humira. Broader immunologic block at a different step in the cytokine pathway.
No material on this site is intended to be a substitute for professional medical advice, diagnosis or treatment. See full Medical Disclaimer.
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FriscoKid
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In reply to McInnis 03 • 1:31p, 4/2/20
AG
McInnis 03 said:
This is ludicrous. We've known about the ability and need of the il6 drugs since South Korea started spreading the word weeks ago...

I'm sorry


There are some outside eyes poking around this board. Maybe someone will pick this up and get it to the right people.
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Marcus Aurelius
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In reply to dermdoc • 1:33p, 4/2/20
AG
It seems to be a neutrophilic explosion. So I think that's why there hasn't been a lot of luck with steroids. But I follow you.
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dermdoc
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In reply to Marcus Aurelius • 1:37p, 4/2/20
AG
Marcus Aurelius said:
It seems to be a neutrophilic explosion. So I think that's why there hasn't been a lot of luck with steroids. But I follow you.
Check your pm.
No material on this site is intended to be a substitute for professional medical advice, diagnosis or treatment. See full Medical Disclaimer.
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plain_o_llama
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In reply to Marcus Aurelius • 1:46p, 4/2/20
Obvious caveats about quackery.....
Someone pointed to this somewhat fringe article over a week ago. The discussion in the last couple of days about the potential use of blood transfusions reminded me of it.

https://www.researchgate.net/publication/340253197_How_to_cripple_SARS-COV-2_virus_with_Ozone_treatment_Thiol_groups_in_viruses_and_SARS-COV-2

Even if the proposed mechanism is wrong, perhaps there is something else going on by "oxidizing" blood that is helpful.
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AggieBax00
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In reply to Marcus Aurelius • 1:58p, 4/2/20
AG
Marcus Aurelius said:
Witnessing another one. Symptom day 10 sudden huge spike in ferritin, CRP, LFTs and neutrophil/lymphocyte ratio. Chest x-ray ARDS exploding. Max vent, proned. New onset renal failure and shock. Depressing. Nothing to do but watch the inevitable play out. Steroids? Can't get compassionate IL-6 inhibitors now.
I don't understand a lot of this, but I do understand ARDS and proned. My MIL had breast cancer, and after 6 months of chemo, she was admitted into the hospital on Memorial Day 2016 very unresponsive with labored breathing. She suffered ARDS, and was eventually put on a vent via a tracheotomy and put into a RotoProne Bed. After over a month and a half in ICU, we had to finally make the decision to take her off the vent.

Very sombering, and prayers for you all fighting on the front lines.
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Infection_Ag11
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In reply to goodAg80 • 2:00p, 4/2/20
AG
goodAg80 said:
Marcus Aurelius said:
Witnessing another one. Symptom day 10 sudden huge spike in ferritin, CRP, LFTs and neutrophil/lymphocyte ratio. Chest x-ray ARDS exploding. Max vent, proned. New onset renal failure and shock. Depressing. Nothing to do but watch the inevitable play out. Steroids? Can't get compassionate IL-6 inhibitors now.
Why not?


Outside of select centers, you pretty much have to enroll the patient in a clinical trial in order to get them right now.
No material on this site is intended to be a substitute for professional medical advice, diagnosis or treatment. See full Medical Disclaimer.
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Charpie
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2:03p, 4/2/20
goodAg80
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In reply to Infection_Ag11 • 2:20p, 4/2/20
AG
Infection_Ag11 said:
goodAg80 said:
Marcus Aurelius said:
Witnessing another one. Symptom day 10 sudden huge spike in ferritin, CRP, LFTs and neutrophil/lymphocyte ratio. Chest x-ray ARDS exploding. Max vent, proned. New onset renal failure and shock. Depressing. Nothing to do but watch the inevitable play out. Steroids? Can't get compassionate IL-6 inhibitors now.
Why not?


Outside of select centers, you pretty much have to enroll the patient in a clinical trial in order to get them right now.
Thanks for answering
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CT75
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In reply to Marcus Aurelius • 2:21p, 4/2/20
AG
Marcus Aurelius said:
It seems to be a neutrophilic explosion. So I think that's why there hasn't been a lot of luck with steroids. But I follow you.
How about low dose morphine temporarily? My father, 92 at the time, had a 'storm type' respiratory event a few years back (don't know that is what it was) while in the hospital. We thought he was dying before our eyes and the cardiologist gave him morphine just to make him comfortable. It eased his symptoms and he pulled through after about 4 hours. I have seen some papers on morphine and its effect on a cytokine storm...but they are way too technical for me to understand.
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ham98
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In reply to Infection_Ag11 • 2:22p, 4/2/20
Infection_Ag11 said:
goodAg80 said:
Marcus Aurelius said:
Witnessing another one. Symptom day 10 sudden huge spike in ferritin, CRP, LFTs and neutrophil/lymphocyte ratio. Chest x-ray ARDS exploding. Max vent, proned. New onset renal failure and shock. Depressing. Nothing to do but watch the inevitable play out. Steroids? Can't get compassionate IL-6 inhibitors now.
Why not?


Outside of select centers, you pretty much have to enroll the patient in a clinical trial in order to get them right now.
Is there also a supply issue or is this regulatory?
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Kool
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In reply to Marcus Aurelius • 2:31p, 4/2/20
AG
Marcus Aurelius said:
It seems to be a neutrophilic explosion. So I think that's why there hasn't been a lot of luck with steroids. But I follow you.
That's odd, isn't it? I would typically think it would be lymphocytic and not neutrophilic. Or is this particular patient's storm just manifesting differently?
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dermdoc
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In reply to Kool • 2:36p, 4/2/20
AG
Kool said:
Marcus Aurelius said:
It seems to be a neutrophilic explosion. So I think that's why there hasn't been a lot of luck with steroids. But I follow you.
That's odd, isn't it? I would typically think it would be lymphocytic and not neutrophilic. Or is this particular patient's storm just manifesting differently?
Tumor anti necrosis factor meds like Enbrel and Humira lower neutrophil counts by 20%. And derms and rheums usually have samples of these in their offices. And rheumatoid maybe even have remicade which they infuse in their offices.

I think I would prefer those over bolus steroids.
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Marcus Aurelius
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In reply to Kool • 2:39p, 4/2/20
AG
When their N/L goes over 20 the survival rate is zero. Seems the lymphocytes are being decimated. I think it's an important pathophysiology mechanism of this severe disease
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JD Shellnut
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In reply to Infection_Ag11 • 2:46p, 4/2/20
AG
Infection_Ag11 said:
goodAg80 said:
Marcus Aurelius said:
Witnessing another one. Symptom day 10 sudden huge spike in ferritin, CRP, LFTs and neutrophil/lymphocyte ratio. Chest x-ray ARDS exploding. Max vent, proned. New onset renal failure and shock. Depressing. Nothing to do but watch the inevitable play out. Steroids? Can't get compassionate IL-6 inhibitors now.
Why not?


Outside of select centers, you pretty much have to enroll the patient in a clinical trial in order to get them right now.


You would figure they would loosen the rules on these meds a bit due to the pandemic.
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Kool
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In reply to Marcus Aurelius • 3:05p, 4/2/20
AG
Marcus Aurelius said:
When their N/L goes over 20 the survival rate is zero. Seems the lymphocytes are being decimated. I think it's an important pathophysiology mechanism of this severe disease


Thanks. Good grief, what a bizarre virus. It's obviously not reading the same textbooks I read in Med school. Ugh
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dermdoc
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In reply to Kool • 3:15p, 4/2/20
AG
Kool said:
Marcus Aurelius said:
When their N/L goes over 20 the survival rate is zero. Seems the lymphocytes are being decimated. I think it's an important pathophysiology mechanism of this severe disease


Thanks. Good grief, what a bizarre virus. It's obviously not reading the same textbooks I read in Med school. Ugh
So we need to block the immune system at the point where it stimulates neutrophils. Reminds me of how parasites preferentially stimulate eosinophils and cause Loeffler's which I have actually had a case secondary to cutaneous larva migrans.

Since the TNF drugs decrease neutrophils, seems like it is definitely worth a shot. Maybe give the plaquenil cocktail to suppress the virus and use the TNF factors to halt the cytokines storm?

No material on this site is intended to be a substitute for professional medical advice, diagnosis or treatment. See full Medical Disclaimer.
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AggieChemist
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3:21p, 4/2/20
AG
What would happen if you tried to treat this runaway inflammation with estrogen?
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Player To Be Named Later
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In reply to AggieChemist • 3:27p, 4/2/20
AG
AggieChemist said:
What would happen if you tried to treat this runaway inflammation with estrogen?


Glad you aren't asking that question on the OB
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Ag In Ok
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In reply to Marcus Aurelius • 3:31p, 4/2/20
AG
Are the hospitals in the area around you at max bed capacity?
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Marcus Aurelius
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In reply to Ag In Ok • 3:37p, 4/2/20
AG
No. But our large university hospital that has 52 COVID-19 pts is near capacity. Once that happens we will get deluged. We are 400 beds. I believe the 4/15-4/20 peak theory.
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Ag In Ok
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3:44p, 4/2/20
AG
Thank you - curious to see how the UW projections are holding from those in the field. My jaw dropped when i saw what they projected for Alabama. Keep fighting the good fight Hero!
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Ranger222
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3:47p, 4/2/20
AG
I've seen some discussions about anti-TNF-alpha agents in recent days.

Reasoning:
Quote:
TNF released by IMMs also promotes the apoptosis of both lung epithelial cells and endothelial cells (unpublished observation). Apoptosis of epithelial and endothelial cells compromises lung microvascular and alveolar epithelial cell barrier resulting in vascular leakage and alveolar edema ultimately resulting in hypoxia.

Exuberant inflammatory responses caused by pathogenic hCoV diminish the T cell response, in the case of SARS-CoV infection via TNF-mediated T cell apoptosis, thus resulting in uncontrolled inflammatory response.

Studies from animal models show a significant contribution of TNF to acute lung injury and impaired T cell responses in SARS-CoV-challenged mice. In vivo neutralization of TNF activity or infection of mice lacking TNFR provides protection against SARS-CoV-induced morbidity and mortality. However, it is to be noted that TNF was not detected in the serum of SARS patients at least during later stages of infection.

From Stanley Perlman's group at Iowa: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079893/
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dermdoc
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In reply to Ranger222 • 3:56p, 4/2/20
AG
Further thoughts on this. Anti TNF meds do not seem to block I L 6. Steroids do. So I would give both.
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chigger
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5:27p, 4/2/20
AG
When you say hypertension, is that controlled or not? Still haven't seen a lot of clarification on that. Also do you think that had any significant effect on the outcome or just that it is present.
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Necrosis
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5:34p, 4/2/20
AG
Has anyone seen the articles discussing the direct hemoglobin disruption caused by the virus? Could be the cause of the profound hypoxemia due to the disruption of the hemoglobin oxygenation curves similar to Methemoglobinemia. Could this virus be a hemoglobinopathy?
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Marcus Aurelius
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In reply to Necrosis • 5:39p, 4/2/20
AG
Good question. Don't think it's methemogolbinemia because in my pts PO2 is tracking with pulse oximetry accurately. I don't think it is causing hemiglobinopathy as I have not seen profound anemia in these pts. But - anecdote.
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