Discussion - 2019-nCoV therapeutics

[kiwibird]

https://www.reuters.com/article/us-health-coronavirus-china-roche-hldg-idUSKBN20R0LF?taid=5e5f567438da270001ffeb37&utm_campaign=trueAnthem:+Trending+Content&utm_medium=trueAnthem&utm_source=twitter

BEIJING (Reuters) - China will use a Roche Holding AG arthritis drug to treat some coronavirus patients in severe conditions, health authorities said on Wednesday, as the country seeks to build up treatment regiments to help the infected recover.

Tocilizumab, sold by the Swiss pharma giant under the trade name Actemra, can be prescribed to coronavirus patients who show serious lung damage and show elevated level of a protein called Interleukin 6, which could indicate inflammation or immunological diseases, the National Health Commission said in the latest version of its treatment guidelines published online.

Actemra can help contain inflammation related to Interleukin 6, according to Roche.

[JJackson]

If you are clinician who is likely to have to deal with COVID patient I would recommend this https://www.degruyter.com/view/j/ccl...-2020-0198.xml (pre-publication) which Tetano (many thanks as always) linked to in today's Sci. library dump. It is a meta analysis of patient lab data which includes a number of parameters which deviate from the norm in those patients that subsequently go on to develop severe disease.

Several significant differences were noted between patients who needed admission to the intensive care unit (ICU) and those who did not, especially encompassing higher white blood cell (WBC) count (1.5-fold), higher neutrophil count (1.7-fold), lower lymphocyte count (0.9-fold), as well as higher values of LDH (2.1-fold), alanine aminotransferase (ALT) (1.5-fold), aspartate aminotransferase (AST) (1.8-fold), total bilirubin (1.2-fold), creatinine (1.1-fold), cardiac troponin I (2.2-fold), D-dimer (2.5-fold) and procalcitonin (1.2-fold). As regards this last parameter, the rate of patients with abnormal values admitted to the ICU was over 3-fold higher than that of those who were not (75% vs. 22%; p<0.001). It has also been reported that non-survivors more frequently developed lymphopenia and leukocytosis, along with abnormal values of D-dimer, blood urea nitrogen and creatinine.

[kiwibird]

If you are clinician who is likely to have to deal with COVID patient I would recommend this https://www.degruyter.com/view/j/ccl...-2020-0198.xml (pre-publication) which Tetano (many thanks as always) linked to in today's Sci. library dump. It is a meta analysis of patient lab data which includes a number of parameters which deviate from the norm in those patients that subsequently go on to develop severe disease.

From the Mayo Clinic
But elevated blood urea nitrogen can also be due to:

• Urinary tract obstruction.
• Congestive heart failure or recent heart attack.
• Gastrointestinal bleeding.
• Dehydration, resulting from not drinking enough fluids or for other reasons.
• Shock.
• Severe burns.
• Certain medications, such as some antibiotics.
• A high-protein diet.

also
High values
A high BUN value can mean kidney injury or disease is present. Kidney damage can be caused by diabetes or high blood pressure that directly affects the kidneys. High BUN levels can also be caused by low blood flow to the kidneys caused by dehydration or heart failure. Many medicines may cause a high BUN.

Elevated Creatinine

Some of the causes of high creatinine levels are:

• Chronic kidney disease. Share on Pinterest Intense exercise can result in increased creatinine levels. ...
• Kidney obstruction. ...
• Dehydration. ...
• Increased consumption of protein. ...
• Intense exercise. ...
• Certain medications.

D-dimer is a fibrin degradation product, a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two D fragments of the fibrin protein joined by a cross-link. D-dimer concentration may be determined by a blood test to help diagnose thrombosis. Wikipedia

[Emily]

Towards the end Annie Sparrow says that Remdesivir trial in China is nearing the end and looks good.

https://www.youtube.com/watch?v=m28UufGwyTw

[kiwibird]

Thank you to Gert for this information.
Gert van der Hoek
Editor, Senior Moderator

• Join Date: Aug 2006
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#1 France, message from MOH: Taking anti-inflammatory drugs (ibuprofen, cortisone, ...) could be a factor in worsening the infection

Today, 07:50 AM
Via Twitter a messag from Minister of Health Olivier V?ran:

Taking anti-inflammatory drugs (ibuprofen, cortisone, ...) could be a factor in worsening the infection. If you have a fever, take paracetamol.
If you are already on anti-inflammatory drugs or in doubt, ask your doctor for advice.

h/t https://twitter.com/oli3be

Olivier V?ran (@olivierveran) on Twitter
https://twitter.com
Tags: None

[bertrand789]

ah bon ,
EXCLUSIF - Coronavirus : ? On sait gu?rir la maladie ?, affirme l'infectiologue Didier Raoult

https://www.lesechos.fr/idees-debats...raoult-1186129

https://www.youtube.com/watch?v=n4J8kydOvbc&t=410s

http://didierraoult.com/

[JJackson]

I asked in an earlier post if anyone knew about TCM (Traditional Chinese Medicine) treatments and trials and there is now a paper covering this. I have so many papers I have downloaded and working through I have only skimmed this one so far but it has tables of what was used, which trials are on going what stage they are up to and if they are randomized or controlled clinical etc.
Seeing as China seems to have got better control of COVID than anyone else and most of their patients (85%) were on some type of TCM I think it is as important to see the results of these as it is to see the results for everything being tried in the west.
Link https://www.ijbs.com/v16p1708.htm

[JJackson]

It turns out that cortico-steroids may be useful if given at the right time in combination with an IL6 blocker later. If the steroids are given too early they mess up the adaptive immune response but in mid infection they help but the patient may already be heading onto an immune over reaction and if they do not respond then the dampening of the IL6 cytokines slows the recruitment of more damaging neutrophils to the site of infection. Daniel has been trialing various drugs, we are all reading about in the press, in his ICU with marginal benefits but says this works in that it is obvious to see without any trial protocols.
TWiV 598 about 10mins in. https://www.microbe.tv/twiv/

This looks at the adaptive immune response if you need a little more background. https://www.youtube.com/watch?v=28gIJ2rrN7I

[kiwibird]

https://www.dailymail.co.uk/news/art...e-effects.html

Swedish hospitals abandon trial of promising malaria drug chloroquine for coronavirus patients after it caused them blinding headaches, vision loss and agonising cramps

• Doctors in Vastra Gotaland pulled plug on medication after adverse side effects
• Swedish patients reported suffering cramps, peripheral vision loss and migraine
• For one in 100 people, can cause arrhythmia, which can lead to fatal heart attack

There are multiple versions of chloroquine - a synthetic form of quinine, which comes from cinchona trees.

Both chloroquine (CQ), branded as Aralen, and counterpart hydroxychloroquine (HCQ), known as Plaquenil, are well-established medicines.

It is unclear which drug the Swedish patients were given, but hydroxychloroquine is thought to be less toxic and causes fewer side effects.
...
Magnus Gisslen, a chief physician at Sahlgrenska University Hospital, said he and colleagues pulled the plug on chloroquine use two weeks ago.

'There were reports of suspected more serious side effects than we first thought,' he told the Gothenburg Post.

'We cannot rule out serious side effects, especially from the heart, and it is a hard-dosed drug. In addition, we have no strong evidence that chloroquine has an effect on COVID-19.'

Professor Anthony Gordon, Chair in anaesthesia and critical care at Imperial College London, told BBC Radio 4's Today programme this morning that there was still no strong evidence the drug could treat coronavirus.

He said: '[Chloroquine] has possibility. We haven't got the strong evidence yet and we need that before we start using it for everybody.

'So I think the right thing to do is to test it in robust clinical trials so we fully understand how it works and also its safety.'

Hydroxychloroquine - a form of chloroquine - is being tested on coronavirus patients at a major trial conducted by the University of Oxford.

[Emily]

This would be a breakthrough in reducing deaths from this illness. A doctor on a Seattle radio station said that about 80% of patients that get the immune dysfuntion bad enough to be ventilated will die. He thought that the immune dysfunction was hitting about 1% of cases. (I think he was talking about cases where people get sick enought to seek care.)

https://flutrackers.com/forum/forum/-2019-ncov-new-coronavirus/united-states-2019-ncov/848098-experimental-drug-believed-to-have-helped-critically-ill-emergency-room-doctor-recover-from-covid-19-autoimmune-cytikine-release-syndrome-drug

(cytokine)

Experimental drug helped critically ill emergency room doctor recover from COVID-19
by Kara Kostanich, KOMO News Reporter
Thursday, April 9th 2020

...
He was first treated at Evergreen Hospital and was then moved to Swedish where doctors tried an experimental drug called Actemra.

Swedish Hospital said they believe the experimental drug helped Padgett recover.

“It would be fair to say we have treated patients with this medicine who have gotten quite ill and gotten better,” said Dr. Krish Patel who is the director of the lymphoma program at Swedish Cancer Institute First Hill.

The drug is showing promise in COVID patients whose bodies have a vigorous immune response to the virus.

“We do know when the immune system is overactive is can make the patient very sick in a short amount of time,” said Patel.

[JJackson]

TWiV 600 is out and excellent, as always. Daniel Griffin has been giving a weekly update on his thoughts based on what is working for his ICU in NY. They have been refining the regime they have been using which he outlined in TWiV 598 (see post 23 above). For clinicians treating COVID patients I would strongly recommend listening.
https://www.microbe.tv/twiv/twiv-600...comment-133943
In addition to the previous treatments they are now looking a D-dimer levels and have concerns about some large clots so are introducing anti-clotting agents. Also Dr. Gattinoni's comments seem pertinent to their findings re. ARDS not being typical and needing a different clinical approach.
https://flutrackers.com/forum/forum/...tress-syndrome

[sharon sanders]

Please see:

JAMA: Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19) A Review - April 13, 2020

[yielddude]

This Cytosorb therapy just approved in US under emergency use authorization ... helps with cytokine storm, webinar tomorrow.
https://cytosorb-therapy.com/en/even...al-experience/

[JJackson]

Do you know when it is? There is a time 1:00 pm - 2:30 pm but no indication of which time zone - GMT, EST etc.

[yielddude]

I believe it is 7am EST, that is what clicks up when I go to the start button for tomorrow. And on one site says this ...

Time

Apr 16, 2020 01:00 PM in Amsterdam, Berlin, Rome, Stockholm, Vienna
which I believe is a 6 hour difference to EST. I admit it is not clear though.

[kiwibird]

https://dominicanewsonline.com/news/...inical-trials/

A clinical trial is now being held for a vaccine aimed at activating the immune system to combat COVID-19 says The director of research at the Centre for Genetic Engineering and Biotechnology, Dr Gerardo Guillen.

Dr. Guillen said during a recent television interview that the drug, called CIGB 2020, is undergoing trials at the Luis Diaz hospital in Havana with volunteer patients suspected of being carriers of the disease.

According to Dr. Guillen there are 41 vaccine projects around the world and only 5 have started their first studies in patients.

He stressed that this current project will take some time develop: “This is a future project that will allow, in a long-term control of the disease, if there is a re-emergence, having a specific vaccine.”