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Discussion - 2019-nCoV therapeutics

If you are clinician who is likely to have to deal with COVID patient I would recommend this https://www.degruyter.com/view/j/cclm.ahead-of-print/cclm-2020-0198/cclm-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.
 
If you are clinician who is likely to have to deal with COVID patient I would recommend this https://www.degruyter.com/view/j/cclm.ahead-of-print/cclm-2020-0198/cclm-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
 
Thank you to Gert for this information.
Gert van der Hoek
Editor, Senior Moderator
  • Join Date: Aug 2006
  • Posts: 22552
#1 [h=2]France, message from MOH: Taking anti-inflammatory drugs (ibuprofen, cortisone, ...) could be a factor in worsening the infection[/h] 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
fetch

Olivier V?ran (@olivierveran) on Twitter
https://twitter.com
Tags: None
 
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
 
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
 
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.
 
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...-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.
 
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
 
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.
 
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.”
 
https://www.fool.com/investing/2020/04/16/why-gilead-sciences-stock-is-on-fire-today.aspx
Why Gilead Sciences Stock Is on Fire Today

Its COVID-19 treatment could be a game changer.

George Budwell(TMFGBudwell)

Apr 16, 2020 at 6:15PM
Author Bio

What happened

Shares of the large-cap biotech Gilead Sciences (NASDAQ:GILD) jumped by as much as 16.1% in after-hours trading Thursday afternoon. The biotech's stock leaped higher after an encouraging report by the science and medical news website STAT suggesting that Gilead's antiviral medication remdesivir may be effective at treating patients hospitalized with severe cases of COVID-19.
While the preliminary data shouldn't be taken as gospel by either patients or investors, these initial results are impressive nonetheless. In one trial by the University of Chicago Medicine, for instance, researchers reported that the vast majority of patients treated with remdesivir were discharged in less than a week, and only two patients died during the study...

Will need more details on study.
 
I know nothing about Chinese medicine but it has been incorporated extensively in their treatment plans, does anyone know what they have been using and what benefits it is reported to have? Any controlled trials data?

https://flutrackers.com/forum/forum...cov-2-a-case-predicted-by-the-theory-of-chaos
In an article published in the highly
influential Medical Journal, Lancet, Cinati et al. [31] showed that the compound,
Glycyrrhizin from liquorice roots which is a key ingredients of Yin and Yang Herbal
Medicines (YYH Medicine) used to treat patients infected with SARS-COV and SARSCOV-
2 was quite effective at inactivating SARS-COV. Wang et al. [32] reported that a
Yin and Yang Herbal Medicine Formula (YYH Medical Formula), Shufeng Jiedu
Capsule in conjunction with anti-Virals, Lopinavir/Ritonavir (Kaletra) and Arbidol, was
able to treat four patients infected with SARS-COV-2 and who had mild or severe
pneumonia. Three of the four patents had much improved pneumonia associated
symptoms and two patients were discharged with confirmed negative SARS-COV-2 by
PCR. The molecular mechanism of actions of the YYH medical Formula is unknown.
However, according to the Principles of Yin and Yang Herbal Medicine (YYH
Medicine), the Yin and Yang Herbal Medical Formula (YYH Medical Formula), Shufeng
Jiedu Capsule (SJC) targets the lungs. (It is indeed quite amazing that the Practitioners
knew that they could use the Shufeng Jiedu Capsule (SJC) to target the lung diseases.).
Other molecules obtained from Yin and Yang Herbal Medical Formula (YYH Medical
Formula), including Baicalin, Scutellarin, Hesperetin and Nicotianamine which have
been reported to possess molecular properties that could allow them to prevent the
interactions between SARS-COV-2 and the human cell Protein Receptor ACE2 [34]
which has been shown to be essential for SARS-COV-2 to gain entrance to its host cells
in the lungs [35]. The use of Hydroxychloroquine for the treatment of COVID-19 [36-39]
that is currently being touted by President Donald ***** [40] has no more scientific
foundation than Yin and Yang Herbal Medicine Formula (YYH Medical Formula) like
Shufeng Jiedu Capsule (SJC) [32] or Glycyrrhizin [31] as they have been reported to be
effective at preventing the replication of SARS-COV and SARS-COV-2. Irrespective of
the molecular Principles of Yin and Yang Herbal Medicine (YYH Medicine), it must be
noted that the current drug of choice for the treatment of Malaria, Arteminisin and
derivatives were discovered following their purification from a Yin and Yang Herbal
Medicine Formula (YYH Medical Formula), by Tu Youyou and co-workers [41,42] who
were awarded the Nobel Prize for Physiology and Medicine in 2015 by the Nobel
Committee. In the field of drug development, Tu Youyou can be regarded as the
equivalent of Marie Curie who discovered Radium and the principles of Radiotherapy. It
would not be too surprising if a useful and successful drug for the treatment of COVID-
19 and SARS-COV-2 infection emerges from the centuries old recipes of Yin and Yang
Herbal Medicine Formula (YYH Medical Formula) again.
 
https://www.hhs.gov/sites/default/fi...ay1_panel2.pdf
SARS-CoV-2/COVID-19 Medical Countermeasures Task Force
Page 28
SARS Vaccine Complications
Vaccine efficacy in aged populations can reduce
performance
Heterogeneous group 2b SARS-like CoV pool may vary
by as much as 35% (compared with SARS)
Th2 Immune Pathology after Vaccination
– DIV SARS-CoV Vaccine + Alum Adjuvant (J Virol. 2011 Dec;85(23):12201-15;
J Immunol. 2008 Nov 1;181(9):6337-48, J. Infect. Dis. 60:106–112)
– Adjuvanted S glycoprotein Vaccines (JCI Insight. 2019 Feb 21;4(4). pii:
123158; J Virol. 2015 Mar;89(6):2995-3007)
Evidence for Enhancing Antibodies
– Primates (ACS Infect Dis. 2016 May 13;2(5):361-76)
– Cell Culture (Biochem Biophys Res Commun. 2014 Aug 22;451(2):208-14,
Clin Exp Immunol. 2005 Sep;141(3):500-8)


https://insight.jci.org/articles/view/123158
Adjuvanted S glycoprotein Vaccines (JCI Insight. 2019 Feb 21;4(4). pii:
123158
The low rate of ALI and interval between lung inflammation resolution and antibody production, however, makes Chinese macaques an ideal animal model for the present study. Using vaccination and passive immunization, we conditioned anti-S antibody titers in macaques during the early stage of infection when ALI was not typically observed. We found that prior administration of anti–S-IgG led to massive accumulation of monocytes/macrophages in the lungs within 2 dpi. This result is consistent with previous reports, in which mice given the SARS vaccine exhibited an immunopathologic lung reaction after the subsequent challenge with SARS-CoV (18, 19). Moreover, in SARS patients, clinical course and outcome are more favorable in children younger than 12 years of age compared with adolescents and adults (44), indicating that prior alternative CoV infection might play a role in driving enhanced pulmonary inflammation. A recent study reported that pathogenic immune complexes promoted lung injury during the 2009 H1N1 pandemic (16). It remains unknown whether immune complexes may also play a role in driving ALI during SARS-CoV infection.
 
Translation Google

Covid-19: Covid-Organics, this remedy that Madagascar has validated

04.21.2020,
-
Against the advice of the WHO, the Madagascan president validated the trials for a treatment based on the well-known artemisia plant in the fight against malaria.

The Madagascan president, Andry Rajoelina is convinced of this: Madagascar is holding an effective drug against Covid-19. It is the Covid-Organics developed by the Malagasy Institute of Applied Research and which contains artemisia or Artemisia annua. A fern-like plant from the traditional Chinese pharmacopoeia grown on the Big Island to fight against malaria, against the advice of the WHO. This discovery seems to have had an impact on the decision of the Head of State to deconfinate the three main cities of the country as of Monday, April 20.

A miracle cure?

After announcing ten days ago the existence of a remedy against the coronavirus in Madagascar, the President of the Republic Andry Rajoelina put an end to the suspense. "Today, I officially announce here the success and the good results of the tests of our remedy," he said, "we can say that it gave a conclusive result on the patients of Covid-19 in Madagascar and that it can limit and lessen its effects on the human body. "

It is the first time that a leader has mentioned artemisia. The World Health Organization (WHO) has recognized that certain traditional medicines and remedies "can alleviate the symptoms" of the coronavirus, but recalled that "there is no evidence that these substances can prevent or cure the disease". The organization even voted in 2007 a resolution "which calls for a progressive withdrawal of monotherapies based on oral artemisinin from the markets". Artemisia is banned in several European countries.

Recourse to the traditional pharmacopoeia

The announcement of the first cases of people infected with Covid-19 has caused in Madagascar a great revival of interest in a whole series of medicinal plants or products such as ginger and lemon supposed to cure or, at the very least, protect from virus. In Madagascar, Imra has been working for several weeks on a treatment against Covid-19. The researchers therefore relied on the results obtained with the Covid-Organics already used to fight against malaria.

According to President Rajoelina "the patients treated with Covid-Organics have been cured". "Patients in respiratory distress have been out of the woods and have already been discharged from the hospital," he added. According to the latest report, 121 cases of contamination by Covid-19, including 39 now considered cured, have been officially reported on the Big Island. None caused the death of a patient.

The opportunity for the head of state to castigate the mentality of certain people who do not trust their leaders or their researchers. According to the national press, Covid-Organics could propel Madagascar to the forefront of the international medical scene and even shake up the world of finance. Artemisia is produced mainly in Madagascar, Africa and Asia.

The stakes are high for the African continent, which records 92% of the 445,000 annual deaths from the disease each year and 90% of the 219 million cases worldwide. Inexpensive herbal medicine would be an advantage over the often more expensive, rare or fake drugs.

In five years, several Artemisia Houses, an association which promotes the use of artemisia founded by the Frenchwoman Lucile Cornet-Vernet, have been created in nearly 23 countries on the continent: Senegal, C?te d'Ivoire, Congo and many others. For this association, it is enough to take the plant in herbal tea for seven days for it to cure and prevent malaria.

Warnings against artemisia

Historically, the virtues of artemisia were revealed to Westerners during the Vietnam War. Indeed, the Americans who fought in the rice fields were treated with chloroquine, a synthetic drug. For their part, the Vietnamese had nothing but died in droves of malaria. For the record, some veterans have even declared that malaria is more formidable than the G.I's. The North Vietnamese then called the Chinese to the rescue who provided them with Artemisia annua to treat the Vietnamese fighters. However, the scientific community is concerned about the side effects of artemisia and remains skeptical about its effectiveness.

The National Academy of Medicine in France warns. If the molecule of artemisinin contained in one of the varieties of artemisia is effectively used in the majority of the antimalarial drugs, "it is its association with other molecules which is necessary to effectively cure the disease by delaying the appearance of resistances “, Recalls Professor Sandrine Houz?, parasitologist at the Bichat hospital in Paris. Not all artemisia species contain artemisinin, she says. And, unlike the tablets which guarantee a constant dosage, the concentration of artemisinin contained in the plant varies according to its mode of culture.

The Madagascan president has already indicated that his "remedy" would be prescribed in the form of syrup "to all students to enable them to protect themselves against the pandemic". "We will gradually restore the normal course of life of the population and their livelihoods," said President Rajoelina in a televised speech, "we will start by doing it for half a day, in the morning from 6 am to 1 pm hours ”.

From Monday morning, public transport will resume their service in the capital Antananarivo and in Fianarantsoa (center) and Toamasina (east) and the schools will reopen for certain classes on Wednesday, he said. The inhabitants will however not be able to “leave their city” and their deconfinement will pass by the obligatory port on the public highway of masks which will begin to be distributed as of Monday. Those who do not wear it will be punished with community service, threatened the head of state.


Le Point / MCP, mediacongo.net

https://www.mediacongo.net/article-a..._a_valide.html
 
https://www.fiercepharma.com/pharma...or-at-least-five-years-says-ai-based-forecast
Vaccines
It could take 5 years for 2 leading COVID-19 vaccines to debut, AI analysis finds
by Arlene Weintraub |Apr 17, 2020 11:36am
...
Global analytics firm Clarivate took a look at vaccines from two companies that have entered clinical trials—Moderna and Inovio—and came to a sobering conclusion: It will take at least five years for either vaccine candidate to complete the development process through full regulatory approval. And neither company has a high probability of success, Clarivate told FiercePharma....
 
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