Health Professionals and COVID-19

[o_e_l_e_o]

I know there are a few other doctors and healthcare workers on here, and I'm interested in talking with any other health professionals who are currently dealing with the COVID-19 situation, particularly anyone working with the critically ill in secondary care, emergency medicine, intensive/critical care, anesthesiology, etc. The reports we are getting from front line staff in Italy are very grim - hospitals being utterly overwhelmed and doctors having to choose which patients will get the few remaining resources and which patients will simply be palliated. I'm interested to hear any other first hand accounts of the situations you are dealing with. We have a few patients in ICU, but nothing unmanageable yet. We have started to convert adjacent high dependency areas in to additional ICU/ventilated beds. Elective work is being cancelled. We expect to be in a similar situation to Italy within a couple of weeks at most.

We are starting to get some data from intensivists in Italy regarding optimum treatment strategies, which we are all trying to disseminate as far and wide as possible. I'll share them in the next post. If you have other guidelines, protocols, SOPs, treatment strategies, I'd be keen to share them too. We are generally treating with conventional ARDS protocols, but seeing a high rate of progress to APRV and proning, even with high levels of permissive hypercapnia.

Self moderated to keep spam and nonsense to a minimum.

[o_e_l_e_o]

A good summary of evidence so far: https://emcrit.org/ibcc/COVID19/

The following images are translated from a meeting of GiViTI, which is the Italian Intensive Care society (click for full size):

Some of the information from the first image has been lost in translation.
P/F input is obviously P/F ratio.
Labs show increase in LDH and CK, and hypoalbuminemia.

[o_e_l_e_o]

Some more resources.

A one sheet summary from an intensivist in Seattle:



Airway management guidelines from a combined working group of UK societies:

https://icmanaesthesiacovid-19.org/airway-management

[TECSHARE]

I am seeing reports that people who take ACE inhibitors and anti-inflammatory drugs may be more susceptible. Do you have any information on this?

[o_e_l_e_o]

I am seeing reports that people who take ACE inhibitors and anti-inflammatory drugs may be more susceptible. Do you have any information on this?

Nothing beyond anecdotes, a lot of which are coming from social media and therefore notoriously unreliable. For example this message which has been widely circulated online regarding "4 young people in a serious condition" who were taking NSAIDs, which was called out as being fake by the society who supposedly released it - https://www.thejournal.ie/ibuprofen-cuh-coronavirus-whatsapp-5047311-Mar2020/

The underlying mechanism being proposed is that NSAIDs and ACE inhibitors cause up-regulation of the ACE2 receptor, and it is this receptor which allows SARS-CoV-2 gain entry to human cells. However, there is also evidence that ACE2 exhibits a protective effect in ARDS (acute respiratory distress syndrome), which is what patients with COVID-19 are dying from. The position statement from the European Society of Cardiology is to continue taking anti-hypertensive therapy as prescribed by your doctor, which I would agree with. However, unless you have a strong reason to be taking a NSAID (like rheumatoid arthritis, for example), I would probably be avoiding them and sticking to acetaminophen/paracetamol.

Having said all that, it makes little difference to my individual practice in intensive care. I couldn't tell you the last time I used a NSAID in intensive care, and the vast majority of our patients with severe infections, sepsis, multi-organ failure, etc. are hypotensive, rather than hypertensive, and generally have most, if not all, of their anti-hypertensive medication stopped during their time with us.

[fillippone]

I posted a very intresting resource on another Corona Related thread.
It's very technical, albeit in italian, but you can autogenerate subtitle and try to understand it.
https://bitcointalk.org/index.php?topic=5220206.msg54044506#msg54044506

Hope it helps.

[franky1]

things like ACE inhibitors and diabetic medication are more linked to the fact that without medication the body is under extra pressure to try cirulating oxygen around your body

for instance diabetic patients can get neuropathy and other things. so their heart and lungs have to work extra. to circulate blood/oxygen
for instance people with low blood pressure end up having an enlarged heart to compensate. but if that large heart then goes above a certain heart rate they can then have bad issues. but this enlarged heart is trying to push more oxygenated blood around your body. so ace inhibitors just try to prevent your heart going too high.. but your heart is still trying to push more oxygen around..

soo.. when your lungs are under stress from breathing due to a cold/flu/pneumonia. this takes a toll on your bodies ability to oxygenate anyway. and like i said for those with diabeties and heart issues this is even more severe.

..
however its is very very important to note that it is NOT the heart/diebetes medication thats the problem. its the underlying health issue before getting the flu.
if you stop taking your heart/diabetic medication you are actually making your problems worse

the notes about medication is not to tell people the medication is a risk. but instead to indicate to doctors and people that having to take the medication means you obviously already have a circulatory problem and its people with circulatory problems that are at risk
in short. its easy to list the vulnerable by just looking at prescription lists of people taking medication related to certain health risks rather then trying to read through decades of every patients patient records

again the medication is not the risk. its the easy identifier of people with underlying health risks. the medication helps reduce the risk so dont stop taking it. the medication just identifies you as having an underlying health issue

(yea i repeat myself because some people dont get it first time)
also things like ibuprofen are not a good mix with underlying heart issues. so yea taking ibuprofen is not going to help your underlying heart condition. thus not gonna help if you become unwell

[Spendulus]

Temperature, humidity, and latitude analysis to predict potential spread and seasonality for COVID-19

https://poseidon01.ssrn.com/delivery.php?ID=150124106095080127020091126090103022063075036012049018106112005097090088113094031067123121063030017007034091090124122121024109020040034053046103085069030123066088119028069037067096072114006127119086001002026112100116105082112074110080072117067093008110&EXT=pdf

Cloroquine treatment suggested

https://www.ncbi.nlm.nih.gov/pubmed/32164085

[o_e_l_e_o]

The WHO have now said essentially the same as what we were discussing above - although the only evidence is from sporadic case reports, it would be wise to avoid NSAIDs for the time being.

Unfortunately I'm having to lock this thread since some individuals are unable to follow the clearly stated purpose of this thread as outlined in the OP. If anyone has useful information to contribute please PM and I will unlock. Feel free to go and discuss non-evidence based conjectures in any of the multiple other COVID-19 related threads.

[nullius]

This is a thread to watch for factual “ground truth” reports (which should be interpreted without panic as collected from those who now having daily experience dealing with a select set of the worst cases).

Doc, there is much misinformation out there.  Would you please offer some practical tips for those who may need to do self-care?

I am not asking for individual medical advice, but rather, for general, practical, medically sound suggestions that are not arrant nonsense.  Given the overload of the medical system and the need for triage, you know that many people will have no choice but to handle their own infections without medical assistance.  I suggest that such people should have access to better information than is being passed in many forum posts that I have been seeing.

Thanks in advance.

[fillippone]

This is a thread to watch for factual “ground truth” reports (which should be interpreted without panic as collected from those who now having daily experience dealing with a select set of the worst cases).

Doc, there is much misinformation out there.  Would you please offer some practical tips for those who may need to do self-care?

I am not asking for individual medical advice, but rather, for general, practical, medically sound suggestions that are not arrant nonsense.  Given the overload of the medical system and the need for triage, you know that many people will have no choice but to handle their own infections without medical assistance.  I suggest that such people should have access to better information than is being passed in many forum posts that I have been seeing.

Thanks in advance.

Check this link sir.
https://bitcointalk.org/index.php?topic=5220206.msg54053333#msg54053333

Those are medics in a real Italian hospital dealing with diagnosis and therapies.
Tis call was recorded yesterday, so pretty state of the art, I guess
 
(computer generate translation available trough subtitles)

[o_e_l_e_o]

-snip-

The first conference call you linked to is summarized in the pictures I uploaded in the second post in this thread. I'll take a look though this second conference call too when I get the time. Many thanks. Given that it also comes from GiViTI though, I doubt very much it will answer nullius' questions regarding self treatment.

In terms of self treatment, there are few suggestions I can offer, unfortunately. There is a little evidence emerging for some specific drug therapies, but there is no specific treatment as of yet, and the majority of these drugs are unavailable to be purchased over the counter. Antibiotics are pointless since it's not a bacteria.

Fortunately for most, if you are young (less than 50 or 60) with no significant comorbidities (hypertension, obesity/diabetes, heart disease, bronchitis/emphysema/smoking seem to be the major ones), then the chances are the infection will be self-limiting and relatively mild. Symptomatic treatment is the same as it would be for any bad cold or flu, with the caveat as discussed above that the advice is to avoid using NSAIDs, which includes drugs such as aspirin, diclofenac, ibuprofen, and naproxen (a list of generic names is available here: https://en.wikipedia.org/wiki/Nonsteroidal_anti-inflammatory_drug#Classification. There are too many individual formulations and brand names to list - check the label of whatever you are buying). Staying hydrated is important, mainly with water and not sugar filled rubbish. Eat as healthy a diet as you can, and try to still get some fresh air. Don't smoke.

Your local jurisdiction should have guidelines regarding how long they would like people with symptoms to self-isolate or similar. The most important thing is to avoid the elderly and people in the high risk groups I listed above, who have a much higher risk of serious illness or death if they do catch it. If you live with someone in one of these categories, then that becomes very difficult. Try to physically separate yourself as much as possible, use different bathrooms if possible, use different plates and utensils, eat separately, and so forth.

Make sure you have enough of a supply of any regular medications you are already taking. Particularly important would be things like inhalers for asthma.

If you do need to seek medical advice, then again follow your local jurisdiction's guidelines. The most common reason for this would be significant shortness of breath, significant fever, lightheadedness/dizziness/fainting. Many areas have a dedicated telephone line to call. If not, call your doctor. This is a preferable first contact rather than showing up in person at a hospital or primary care center or calling an ambulance, unless you (or someone else) feels very unwell and it is a true emergency.

Cover your coughs and wash your hands.

Apologies that that is all very vague, but there is very little specific advice regarding treatment for mild cases other than treating it like you would any other respiratory infection, and trying not to infect others. There's a very good no-nonsense FAQ from Harvard Medical School available here: https://www.health.harvard.edu/diseases-and-conditions/coronavirus-resource-center#COVID

[fillippone]

An Italian Forum user's mother has just been dismissed from the hospital:
https://bitcointalk.org/index.php?topic=5231876.msg54063955#msg54063955


Here the therapy they used:

Quote from: bitbollo on March 14, 2020, 02:47:59 PM
hello @ aga0685, I hope everything goes well.
What medication are they giving your mother?
I ask you (as a pharmacist who deals with experimental drugs) because there are several products that could be used (potentially) but no well-defined protocol .... I hope you will be able to dispel my doubt .... in the meantime a great deal in good luck and a (virtual) hug from me

Now I can answer you much better .. having the medical record it's all easier ...
I hope in this way to have satisfied your curiosity as an "experimental" pharmacist ehehe ...

PERFALGAN (analgesic / antipyretic)
ELETTR REID III (Physiological to rehydrate her) (a couple of days only.. not more ...)
Levofloxacin (antibiotic for bacterial infections)
KALETRA (antiviral aids)
PLAQUENIL (rheumatoid / antimalarial arthritis)
Flowing oxygen.

Interesting the use of Plaquenil, browsing the net I found an article on the Republic dated March 18 in which it seems there have been studies in France on the success of COVID therapy using this drug ..
https://www.repubblica.it/salute/medicina-e-ricerca/2020/03/18/news/coronavirus_il_farmaco_contro_la_malaria_funziona_in_3_casi_su_4-251594568/

My mother came in several days before ..... so it must have been one of the very first to use it ....

Bye!

[o_e_l_e_o]

A quick break down of those treatments for anyone interested:

Perfalgan - this is acetaminophen/paracetamol. Standard treatment throughout the word for fever.

Elettrol Reid III - standard Italian IV fluids. Similar to Ringer's lactate and other compound sodium lactate solutions.

Levofloxacin - an antibiotic. Often in patients with severe viral infections or ARDS, we see super-imposed bacterial infections. Levofloxacin is commonly used for this indication because of its broad spectrum activity against both Gram positive and Gram negative bacteria, including Staph and Strep species.

Kaletra - Lopinavir/ritonavir. These two drugs are both antivirals. They are known as protease inhibitors, and inhibit the production of some proteins which are needed for the virus to multiply. They are widely used the world over in HIV/AIDS treatment regimes. There is reasonable data that this drug is effective against the original SARS-CoV and also against MERS-CoV. There is little data for it at the moment in relation to SARS-CoV-2, but trials are ongoing and it seems a logical option to try.

Plaquenil - Hydroxychloroquine. Used mainly as an anti-malarial, but also displays some anti-viral activity. Interestingly to our discussion above, it may exhibit some inhibitory activity at the ACE2 receptor, in addition to its other mechanisms of action. There is good in vitro data showing it is effective against SARS-CoV-2. In vivo data is sparse, but there are case series from China suggesting good results (however, there are also case series suggesting it makes no difference).

Oxygen - standard treatment for people with acute respiratory distress syndrome.

[bitbollo]

@o_e_l_e_o very useful and interesting topic! it's always a pleasure
[I am a registered pharmacy in Italy, working for a pharmaceutical company (Clinical trials)]

Please find below the last update regarding Kaletra (ALUVIA (r) trade name in EMEA) (originally posted in Italian board section: https://bitcointalk.org/index.php?topic=5231876.msg54065220#msg54065220 )

Kaletra (ALUVIA (r) trade name in EMEA)
It was unable to demonstrate any clinical improvement in the first clinical studies found for COVID-19 (compared to "standard of care").
Long story short:
The trial recruited 199 patients and began on January 18, 2020, when very little is known about this virus and associated clinical conditions.
It is not a complete defeat, at least for the moment.
Probably, some analysts point out, for this trial, have been recruited patients "in bad health condition" and as a bias it may have "distorted" the final result. For greater effectiveness it is necessary to find the "suitable" moment in which to administer such product.

For further information:
https://www.fiercepharma.com/pharma-asia/does-abbvie-s-hiv-drug-kaletra-also-works-covid-19-maybe-not-nejm-study-finds
The news / comments given in an online magazine specialized in the pharmaceutical industry.

https://www.nejm.org/doi/full/10.1056/NEJMoa2001282
Here the full scientific article.

[mindrust]

French lab: plaquenil combined with azithromycin cured patients in a matter of days.

https://twitter.com/XavierDidelot/status/1239937472626331653?s=19



https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-000890-25/FR

Preprint:
https://www.mediterranee-infection.com/wp-content/uploads/2020/03/Hydroxychloroquine_final_DOI_IJAA.pdf

Plaquenil has its side effects, it is not a free pass. It is probably preferable to die by corona.

[bitbollo]

French lab: plaquenil combined with azithromycin cured patients in a matter of days.

https://twitter.com/XavierDidelot/status/1239937472626331653?s=19



https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-000890-25/FR

Preprint:
https://www.mediterranee-infection.com/wp-content/uploads/2020/03/Hydroxychloroquine_final_DOI_IJAA.pdf

Plaquenil has its side effects, it is not a free pass. It is probably preferable to die by corona.

There are some weak points on this data.

This is a small scale trial (25 patients), non blinded and non randomized (it means it can be strongly biased by investigators and you have nothing to compare like "standard of care").  
The picture above isn't clear since what they mean by "no treatment"? Who are these patients? how they select these parameters/patients with "no treatment"? (according to clinical trial register - there is no comparator, no placebo, no standard of care, only IMP investigational medical product).
We don't know when these patients received the treatment (we don't know the really health condition of these subjects at screening).
(according to clinical trial register - Women and men with documented respiratory infection with Coronavirus SARS CoV 2)

Despite this product can sound interesting at first sight (like all treatment when we start a clinical trial ) I guess is a bit early to claim any real effect, and even it should be evaluated in a large scale with strong scientific criteria (randomization, double blind etc)

(just a note about preprint, they are publishing in a "small" journal, Impact Factor: 4.615 (NEJM Impact factor: 70.67))

[o_e_l_e_o]

-snip-

I hadn't seen this paper yet - thanks for bringing it to my attention.

It's interesting. There are some parts of their data which do show a benefit to lopinavir/ritonavir, despite their conclusions that there was no benefit. Looking at table 3, for example, shows a median length of ICU stay being reduced from 11 days to 6 days. This alone would be huge if it was significant, but unfortunately they don't provide a p-value for this. For that reason, I would assume it was not significant, but it certainly warrants further investigation. Halving every patient's ICU stay effectively means doubling ICU capacity, which could save thousands of lives at a time like this when ICUs are being overrun.

Further, my understanding of lopinavir/ritonavir is that it needs to be given early, during the replication phase of the virus. In this study the average time from illness onset to randomization in to the trail was 13 days, which will be well past the peak time, which may explain their disappointing result. I also know many of the trials of these drugs in regards to SARS-CoV and MERS-CoV also included ribavirin. I wonder if this triple combination is being trialed anywhere for SARS-CoV-2?

[mindrust]

I think there is also a war between the pharmaceutical companies.

While some of them promote some specific molecules as the most effective against the Chinese virus, some other companies will say theirs are more effective.

Eventually FDA will have to choose one of those and we all are going to want that one.

Too much money to be made from this.

[bitbollo]

I think there is also a war between the pharmaceutical companies.
....
Too much money to be made from this.

Of course there is "a war" between pharmaceutical companies and it's normal when there is a competition with a "prize".
The term "war" is unfair, this is just competition as any other industrial field.
And this is also positive, since if no one has really interest in finding a cure or develop new treatments, probably like ancient romans, we will die at 30 years old even for a cough or just cold.

While some of them promote some specific molecules as the most effective against the Chinese virus, some other companies will say theirs are more effective

NO.
Clinical trials and generally speaking science isn't working in that way (who speaks more loudly WINS!)
If you have a better product respect other companies you should run a clinical trial in strictly conditions, it mean you should PROVE what are you saying.
(this is the reason there are regulatory agencies...)
Each information you found in a product label, has been evaluated and approved by a third part, and it can be even change amended or update with new informations... since science need to be updated, and the competition will bring more effective medicine.

Eventually FDA will have to choose one of those and we all are going to want that one.

NO.
FDA will no choose ONE OF THOSE but they will normal approve ALL PRODUCTS that meet some criteria.
Since it's better have more weapons then only one (even if strong!)
According to OP we are not here to explain from scratch how it works an entire industry or explain how it works approval of new drugs, so please don't make these assumptions

I also know many of the trials of these drugs in regards to SARS-CoV and MERS-CoV also included ribavirin. I wonder if this triple combination is being trialed anywhere for SARS-CoV-2?

I have found just one trial that will compare these treatments but no combination.
[Probably there are too many side effects for a combination of these three substances/API Active Pharmaceutical Ingredient]
 
Drug: Lopinavir/ritonavir
Drug: Ribavirin
Drug: Interferon Beta-1B
https://clinicaltrials.gov/ct2/show/NCT04276688?term=ribavirin&recrs=a&draw=2&rank=8

[o_e_l_e_o]

Here are some of the old papers which I see being used as an evidence base for trying lopinavir/ritonavir against SARS-CoV-2, which all include ribavirin alongside lopinavir/ritonavir for SARS-CoV or MERS-CoV. As you say bitbollo, I'm not aware of any current trials using this regime against SARS-CoV-2.

Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 2004 Mar; 59(3): 252-6.
https://thorax.bmj.com/content/59/3/252.long

Chan KS, Lai ST, Chu CM, Tsui E, Tam CY, Wong MM, et al. Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study. Hong Kong Med J. 2003 Dec; 9(6): 399-406.
https://www.hkmj.org/abstracts/v9n6/399.htm

Park SY, Lee JS, Son JS, Ko JH, Peck KR, Jung Y, et al. Post-exposure prophylaxis for Middle East respiratory syndrome in healthcare workers. J Hosp Infect. 2019 Jan; 101(1): 42-46.
https://www.journalofhospitalinfection.com/article/S0195-6701(18)30484-5/fulltext


I'd like to keep on topic about evidence based treatment options for SARS-CoV-2, and not about the politics surrounding pharmaceutical companies please. Many thanks.

[af_newbie]

Here are some of the old papers which I see being used as an evidence base for trying lopinavir/ritonavir against SARS-CoV-2, which all include ribavirin alongside lopinavir/ritonavir for SARS-CoV or MERS-CoV. As you say bitbollo, I'm not aware of any current trials using this regime against SARS-CoV-2.

Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 2004 Mar; 59(3): 252-6.
https://thorax.bmj.com/content/59/3/252.long

Chan KS, Lai ST, Chu CM, Tsui E, Tam CY, Wong MM, et al. Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study. Hong Kong Med J. 2003 Dec; 9(6): 399-406.
https://www.hkmj.org/abstracts/v9n6/399.htm

Park SY, Lee JS, Son JS, Ko JH, Peck KR, Jung Y, et al. Post-exposure prophylaxis for Middle East respiratory syndrome in healthcare workers. J Hosp Infect. 2019 Jan; 101(1): 42-46.
https://www.journalofhospitalinfection.com/article/S0195-6701(18)30484-5/fulltext


I'd like to keep on topic about evidence based treatment options for SARS-CoV-2, and not about the politics surrounding pharmaceutical companies please. Many thanks.

https://www.fiercepharma.com/pharma-asia/does-abbvie-s-hiv-drug-kaletra-also-works-covid-19-maybe-not-nejm-study-finds

https://www.npr.org/sections/health-shots/2020/03/21/819099156/might-the-experimental-drug-remdesivir-work-against-covid-19

[bitbollo]

https://www.fiercepharma.com/pharma-asia/does-abbvie-s-hiv-drug-kaletra-also-works-covid-19-maybe-not-nejm-study-finds
.....

I have already posted this news from fiercepharma some days ago please find below also a short summary.

@o_e_l_e_o very useful and interesting topic! it's always a pleasure
[I am a registered pharmacy in Italy, working for a pharmaceutical company (Clinical trials)]

Please find below the last update regarding Kaletra (ALUVIA (r) trade name in EMEA) (originally posted in Italian board section: https://bitcointalk.org/index.php?topic=5231876.msg54065220#msg54065220 )

Kaletra (ALUVIA (r) trade name in EMEA)
It was unable to demonstrate any clinical improvement in the first clinical studies found for COVID-19 (compared to "standard of care").
Long story short:
The trial recruited 199 patients and began on January 18, 2020, when very little is known about this virus and associated clinical conditions.
It is not a complete defeat, at least for the moment.
Probably, some analysts point out, for this trial, have been recruited patients "in bad health condition" and as a bias it may have "distorted" the final result. For greater effectiveness it is necessary to find the "suitable" moment in which to administer such product.

For further information:
https://www.fiercepharma.com/pharma-asia/does-abbvie-s-hiv-drug-kaletra-also-works-covid-19-maybe-not-nejm-study-finds
The news / comments given in an online magazine specialized in the pharmaceutical industry.

https://www.nejm.org/doi/full/10.1056/NEJMoa2001282
Here the full scientific article.

.....
https://www.npr.org/sections/health-shots/2020/03/21/819099156/might-the-experimental-drug-remdesivir-work-against-covid-19

There is an interesting article on EvaluatePharma regarding remdesvir and expense related clinical development
https://www.evaluate.com/vantage/articles/news/corporate-strategy/estimating-cost-covid-19-antiviral-development

Phase III trials of Gilead’s remdesivir are likely to be the most expensive ventures right now; the US biotech has indicated that initial data should emerge before the end of March. This readout represents the world’s nearest-term chance of finding a treatment for the sometimes deadly respiratory symptoms caused by this particular coronavirus.

According to EvaluatePharma Vision’s R&D Costs module, these trials will probably cost Gilead around $150m to run. Estimates of the phase III trials being run in China are also included – the much lower figures reflect the fact that it is substantially cheaper to run studies in this region. A description of how these costs are calculated is below.

Gilead can afford this, of course, and should remdesivir prove effective the commercial return is likely to be huge, notwithstanding the company claiming their efforts are not rooted in the commercial. Roche has booked cumulative sales of $15.9bn of Tamiflu since it was launched in 1999; annual sales peaked at just over $1bn in 2014. These figures exclude sales booked by the other companies that make it

[bitbollo]

Please find HERE a very interesting resource regarding "Genomic epidemiology of novel coronavirus" ¹ with lot of data!

Yesterday² (March 22th 2020) I made this video You can play by clicking here.

[¹ Nextstrain.org aims to provide a real-time snapshot of evolving pathogen populations and to provide interactive data visualizations to virologists, epidemiologists, public health officials, and community scientists. Through interactive data visualizations, we aim to allow exploration of continually up-to-date datasets, providing a novel surveillance tool to the scientific and public health communities.

[² This video has been originally posted in Italian forum section ]

[o_e_l_e_o]

Once more, as stated in the OP, this thread is for evidence based discussion about treatment strategies specific to SARS-CoV-2. Much like discussion surrounding the influenza vaccine on the previous page, discussion about vitamin C megadosing for the common cold is entirely off topic. There are plenty of other threads where such discussion would be more suitable.

[CoinCube]

Once more, as stated in the OP, this thread is for evidence based discussion about treatment strategies specific to SARS-CoV-2. Much like discussion surrounding the influenza vaccine on the previous page, discussion about vitamin C megadosing for the common cold is entirely off topic. There are plenty of other threads where such discussion would be more suitable.

Your thread your rules. I have reposted the information on potential immune boosting supplements here:

https://bitcointalk.org/index.php?topic=5220206.msg54083990#msg54083990

I do disagree that this is off topic. We are just at the start of this and already there is a nationwide shortages of protective gear.

Coronavirus: Pleas go out for healthcare workers facing shortages of protective gear
https://www.msn.com/en-us/news/us/coronavirus-pleas-go-out-for-healthcare-workers-facing-shortages-of-protective-gear/ar-BB11B5Uk

Many front line healthcare workers are very likely to be placed in situations where they must treat patients with insufficient protective equipment. Any comprehensive treatment strategy for SARS-CoV-2 at this point must in addition to the typical treatment algorithms also include the following.

1) Developing a plan for treatment when new supplies of typically disposable protective equipment cannot be obtained.
2) Assessing personnel risk and determining which personnel should or should not be allowed to enter situations that carry high risk for exposure.
3) Risk mitigation for the inevitable high numbers of healthcare worker who will contract this on the job.

I would make the case that immune boosting supplements fall into #3 and are therefore relevant to a discussion of treatment strategies for SARS-CoV-2. However, I realize that that this not the direction you want this thread to go in so I will refrain posting any further discussion of supplements in this thread.

[bitbollo]

Latest updates from FiercePharma and Evaluate about new treatments for COVID-19 infection.
Please find below a short summary and various references.
I will keep posting information about new treatments only on this post (LAST and FINAL EDIT/UPDATE March 27th at 09:34)

I cannot share other informations and I can't update this post anymore because even my company will work in a clinical trial related COVID19 (public announcement not done)
Thanks to all and STAY SAFE!

KALETRA® (ALUVIA®) - Lopinavir/Ritonavir - Abbvie
AbbVie will not enforce global patent rights on all formulations of HIV med Kaletra (Aluvia) as the drug is being evaluated to treat severe COVID-19 in several clinical trials.
The move would free countries to purchase Kaletra generics in the event of a shortage or if the drug is found to be effective in treating COVID-19 patients. ¹

Remdesivir - Gilead
Gilead Sciences temporarily stopped granting patients emergency access to remdesivir under compassionate use due to an “exponential increase” in requests over the last few days, the company said Sunday. Exceptions will be made for pregnant women and children under 18 with severe COVID-19, the disease caused by the novel coronavirus.²

ACTMERA® - Tocilizumab - Genetech (Roche subsidiary)
FDA has approved a randomized, double-blind, placebo-controlled Phase III clinical trial in collaboration with the Biomedical Advanced Research and Development Authority (BARDA) to evaluate the safety and efficacy of intravenous Actemra® (tocilizumab) plus standard of care in hospitalized adult patients with severe COVID-19 pneumonia.³

INOpulse®  - Nitric oxide (iNO) delivery system - Bellerophon
FDA Grants Bellerophon Emergency Expanded Access for INOpulse® for the Treatment of COVID-19 Virus. ⁴

Blood Plasma-Derived Antibodies - Takeda
Takeda Pharmaceutical Co. said its blood plasma-derived therapy against coronavirus currently in development has the potential to be among the first approved treatments for the deadly pathogen.⁵

Chloroquine Phosphate Hydroxychloroquine Sulphate - Ipca Laboratories
The FDA has lifted an import alert on India's Ipca Laboratories, one of makers of chloroquine (Active Product Ingredient) of this anti-malaria drug that could hold promise in managing and treating COVID-19 ⁶

Avigan® Favilavir® - Favipiravir - Fujifilm's
Chinese Clinical trial data demonstrated reduced viral load and improved X-Rays in treated patients.
However Japanese Officials note that it need to be used early, since the drug not appear to be as effective in people with severe symptoms. According to the same reference, it could be approved as early as May ⁷

Sylvant® - Siltuximab - Eusa Pharma
They are running an observational study on compassionate use in patients with serious complications of COVID-19 and the opportunity to generate data to understand the potential for IL-6 blockade in these patients. ⁸

Nafamostat Mesylate [generic drug] - Futhan® -  Nichi-iko Pharmaceutical Co. (producer)
A blood thinner used to treat pancreatitis and kidney disease has been identified as a potential therapy for COVID-19 patients. Clinical trials in Japan possibly set to begin in March 2020 ⁹

PUL-042 - Pulmotect  [new treatment added on this list March 24th 03:53 PM]
This is a prevention study that has lead positive data in preclinical stage. Phase I has been completed. Phase II to be initiated this year according the statement on reference¹⁰

SNG001 - Synairgen [new treatment added on this list March 25th 20:40 PM]
This company will start a Phase II trial (double blind and placebo controlled) in COVID-19 patients according to their statement "imminently"
¹¹

INOmax® - Nitric oxide (iNO) Mallinckrodt [new treatment added on this list March 25th 20:40PM]
They will start to evaluate the evidence of efficacy about their iNO delivery system for pulmonary complications associated with coronavirus.
(first announcement made on March 12th 2020)
¹²

remestemcel-L - Mesoblast [new treatment added on this list March 25th 20:40 PM]
Plans to evaluate its allogeneic mesenchymal stem cell (MSC) product candidate remestemcel-L in patients with acute respiratory distress syndrome (ARDS) caused by coronavirus (COVID-19) ¹³
(first announcement made on March 10th 2020)

(LAST and FINAL EDIT/UPDATE March 27th at 09:33)
I cannot share other informations and I can't update this post anymore because even my company will work in a clinical trial related COVID19 (public announcement not done)
Thanks to all and STAY SAFE!

[There is actually no treatment approved for COVID-19. I am not involved in any of these companies.
Visit FiercePharma or visit Evaluatefor further information and updates on COVID-19.]
[Legend= Brand Name® - API (Active Pharmaceutical Ingredient) - Company Name]

¹ https://www.ft.com/content/5a7a9658-6d1f-11ea-89df-41bea055720b
² https://www.gilead.com/news-and-press/company-statements/gilead-sciences-statement-on-access-to-remdesivir-outside-of-clinical-trials
³ https://www.businesswire.com/news/home/20200323005166/en/Genentech-Announces-FDA-Approval-Clinical-Trial-Actemra
⁴http://investors.bellerophon.com/news-releases/news-release-details/fda-grants-bellerophon-emergency-expanded-access-inopulser
⁵ https://www.bnnbloomberg.ca/drugmaker-takeda-sees-speedy-approval-of-coronavirus-treatment-1.1407334
⁶ https://www.bseindia.com/xml-data/corpfiling/AttachLive/af31e003-575e-4550-b6f2-c1340aec82e9.pdf
⁷ https://pbs.twimg.com/media/ETadjJVWoAAXv-4?format=jpg&name=4096x4096
⁸ https://www.biospace.com/article/releases/eusa-pharma-and-the-papa-giovanni-xxiii-hospital-bergamo-italy-announce-initiation-of-an-observational-case-control-study-of-siltuximab-in-patients-with-covid-19-who-have-developed-serious-respiratory-complications/
⁹ https://www.bnnbloomberg.ca/japanese-researchers-to-test-blood-thinner-for-virus-treatment-1.1407980
¹⁰ https://pulmotect.com/wp-content/uploads/2020/01/20201_Coronavirus_PR_Final.pdf
¹¹ https://www.synairgen.com/wp-content/uploads/2020/03/200318-Synairgen-to-start-trial-of-SNG001-in-COVID-19-imminently-.pdf
¹² https://mallinckrodt.gcs-web.com/node/26576/pdf
¹³ http://investorsmedia.mesoblast.com/static-files/c1428818-0b9f-44f9-bb4f-79ad518002cc

[bitbollo]

Latest clinical trials results posted today March 24th 2020, please find below a short summary with references.

According to this small study, as reported on Fiercepharma hydroxychloroquine has provided disappointing results vs conventional treatment.

...Hydroxychloroquine, a more tolerable form of chloroquine, didn’t top placebo at clearing the coronavirus among mild Chinese patients, or helping them reach normal temperature sooner.
.... used on top of conventional treatments, cleared the virus in 13 (86.7%) cases on day 7, while 14 (93.3%) patients in the control group the virus cleared, according to a study abstract Raffat obtained. One patient on the malaria med progressed to severe during the treatment.
.... The only positive signal was disease progression shown on CT scans, which five hydroxychloroquine cases showed, versus seven in the control group. .... (however) the trial size was simply too small to draw conclusions.

As claimed by the same news on Fiercepharma there is also another trial fail published today in this preprint paper , where subjects have been randomized to lopinavir/ritonavir (Kaletra® also known as Aluvia®) or Umifenovir (Arbidol®) or no antiviral medication as control (2:2:1)

... exploring the efficacy and safety of lopinavir/ritonavir (LPV/r) or arbidol monotherapy treating mild/moderate COVID-19 patients.
... The positive-to-negative conversion rates of SARS-CoV-2 nucleic acid at day 7 and 14 did not show significant differences in the LPV/r group (42.9%, 76.2%), the arbidol group (62.5%, 87.5%) and the control group (71.4%, 71.4%) (all P>0.53). No statistical differences were found among three groups in the rates of antipyresis, cough alleviation, improvement of chest CT or the deterioration rate of clinical status (all P > 0.05).
Overall, 5 (23.8%) patients in the LPV/r group experienced adverse events during the follow-up period. No apparent adverse events occurred in the arbidol or control group.
.... (however) Due to the limitation of small sample size, further verification is needed in the future.

(LAST and FINAL EDIT/UPDATE March 27th at 09:34)

I cannot share other informations and I can't update this post anymore because even my company will work in a clinical trial related COVID19 (public announcement not done)
Thanks to all and STAY SAFE!

[bitbollo]

An interesting list of vaccine projects has been posted on Evaluate Pharma, please find below these updates:

Johnson & Johnson Collaboration with Beth Israel Deaconess Medical Center
Heat Biologics Collaboration with University of Miami
Anges Collaboration with Osaka University
Epivax Collaboration with University of Georgia
Generex Collaboration with Epivax
Arcturus Collaboration with Duke-NUS Medical School
Inovio

[erre]

IMPORTANT NOTICE: the above time values are MEDIANS, not the upper limited of a confidence interval.

Considering that an asymptomatic is no more contagious after 2 weeks because that's the median value is very imprudent (50% will be still contagious if the distribution is gaussian).

This common error is killing people in italy.

[fillippone]

IMPORTANT NOTICE: the above time values are MEDIANS, not the upper limited of a confidence interval.

Considering that an asymptomatic is no more contagious after 2 weeks because that's the median value is very imprudent (50% will be still contagious if the distribution is gaussian).

This common error is killing people in italy.

Very interesting @erre.
Could you please clarify what "immune" means?
I heard, I might be wrong here, that second infections were observed in recovered patients. "Immune" makes me think that second infections aren't even possible.

[erre]

IMPORTANT NOTICE: the above time values are MEDIANS, not the upper limited of a confidence interval.

Considering that an asymptomatic is no more contagious after 2 weeks because that's the median value is very imprudent (50% will be still contagious if the distribution is gaussian).

This common error is killing people in italy.

Very interesting @erre.
Could you please clarify what "immune" means?
I heard, I might be wrong here, that second infections were observed in recovered patients. "Immune" makes me think that second infections aren't even possible.

You are immune when you produce specific antibodies for the disease.
Not every disease grant immunity forever, but it's reasonable that the few observed remission cases are an exception.

[PrimeNumber7]

I am not sure what type of practice you have, however if you were treating a patient with COVID-19, can you explain the reasons why you would prescribe someone Hydroxychloroquine to treat the disease? and also can you explain some of the reasons why you would not prescribe Hydroxychloroquine?

This drug has not been proven in effectiveness in treating COVID-19, however clinical trials required to show proof can take time that hundreds of thousands of people may not have, and there is some anecdotal evidence that it works. 

[franky1]

I am not sure what type of practice you have, however if you were treating a patient with COVID-19, can you explain the reasons why you would prescribe someone Hydroxychloroquine to treat the disease? and also can you explain some of the reasons why you would not prescribe Hydroxychloroquine?

This drug has not been proven in effectiveness in treating COVID-19, however clinical trials required to show proof can take time that hundreds of thousands of people may not have, and there is some anecdotal evidence that it works. 

studies show its effectiveness as a antiviral is not much/any. hense also needing an antiviral as part of treatment. but it has shown some effectiveness at dampening the immuni inflamatory response that causes the breathing distress.

there is not single magic pill and even if able to breathe easier doesnt mean your cured of the actual viral invasion. your just symptomless.
taking these drugs as immuno suppressers when not having an immuno reaction can actually harm you and when you get corona you may end up being worse than you would of if you didnt take it prior to getting corona.

thats why there is stil questions around if its a good enough drug for a certain job and when is best to administer it. as administering it even during ARDS (respiratory distress) can exacerbate the other symptoms

[estenity]

studies show its effectiveness as a antiviral is not much/any. hense also needing an antiviral as part of treatment. but it has shown some effectiveness at dampening the immuni inflamatory response that causes the breathing distress.

there is not single magic pill and even if able to breathe easier doesnt mean your cured of the actual viral invasion. your just symptomless.
taking these drugs as immuno suppressers when not having an immuno reaction can actually harm you and when you get corona you may end up being worse than you would of if you didnt take it prior to getting corona.

thats why there is stil questions around if its a good enough drug for a certain job and when is best to administer it. as administering it even during ARDS (respiratory distress) can exacerbate the other symptoms

thank you for explaining, but a  proportion of patients die from "cytokine storm ", sometimes brutally in the street.
so you have to precise the indications.

[JayJuanGee]

studies show its effectiveness as a antiviral is not much/any. hense also needing an antiviral as part of treatment. but it has shown some effectiveness at dampening the immuni inflamatory response that causes the breathing distress.

there is not single magic pill and even if able to breathe easier doesnt mean your cured of the actual viral invasion. your just symptomless.
taking these drugs as immuno suppressers when not having an immuno reaction can actually harm you and when you get corona you may end up being worse than you would of if you didnt take it prior to getting corona.

thats why there is stil questions around if its a good enough drug for a certain job and when is best to administer it. as administering it even during ARDS (respiratory distress) can exacerbate the other symptoms

thank you for explaining, but a  proportion of patients die from "cytokine storm ", sometimes brutally in the street.
so you have to precise the indications.

I was not sure what cytokine storm was, so I did a quick google search, and I found this short article.

https://www.newscientist.com/term/cytokine-storm/

Of course, there were plenty of other articles, but this one at least gave a quick overview of the concept.

[tvbcof]

thank you for explaining, but a  proportion of patients die from "cytokine storm ", sometimes brutally in the street.
so you have to precise the indications.

I was not sure what cytokine storm was, so I did a quick google search, and I found this short article.

https://www.newscientist.com/term/cytokine-storm/

Of course, there were plenty of other articles, but this one at least gave a quick overview of the concept.

That's what the animal test subjects dropped from in startling numbers before they gave up on the last coronavirus vaccine was attempted 10 years ago.  Just FWIW.  But since this post posses some questions about vaccines it will be deleted on this 'self-moderated' thread.

[bitbollo]

About hydroxychloroquine (HCQ) there is a big HYPE...
Ruling out France, where there is a medical doctor that made the first paper (find below a short analysis) https://bitcointalk.org/index.php?topic=5232377.msg54066125#msg54066125
and announcement in twitter
https://twitter.com/AceClearance/status/1244243333322506240
with AWESOME RESULTS (no twitter is not a peer reviewed scientific journal and peers evaluate papers not conclusions   ) rest of Europe, with EMA authority (European Medicine Agency) has taken a clear position:

European Medicines Agency restricted general use of the drugs—already approved to treat malaria and autoimmune diseases—to patients taking them for approved indications. COVID-19 patients can receive the drugs as part of clinical trials or through national emergency use programs, the EMA said.

https://www.ema.europa.eu/en/news/covid-19-chloroquine-hydroxychloroquine-only-be-used-clinical-trials-emergency-use-programmes

Fun Fact,
as I have highlighted to some USA member   ... most of people continue to speak about HQC thanks to a "presidential support".

"Unlike FDA, European regulators refuse to clear chloroquine for COVID-19 without data"
Chloroquine and hydroxychloroquine have drawn more attention— and certainly more presidential support —than any other drug during the global quest to find an effective coronavirus therapy.

https://www.fiercepharma.com/pharma/europe-locks-down-chloroquine-scripts-as-researchers-china-report-positive-controlled-covid

"The suspect science behind Trump’s chloroquine claims"
Trump’s trumpeting of chloroquine may have encouraged at least one fatal outcome. As we reported, a Phoenix couple who heard Trump’s briefing took doses of a chloroquine preparation they had at hand to treat their fish tank; the husband died and his wife landed in critical condition before recovering.

https://www.latimes.com/business/story/2020-04-01/trump-chloroquine-coronavirus-bad-science-hiltzik-column

[o_e_l_e_o]

-snip-

Where I am working, almost all patients are being randomized in to a trial. One arm of said trials includes hydroxychloroquine therapy. So there isn't really a medical decision to be made regarding treatment - if they are in the treatment arm they receive it, if they are in any of the other arms, they don't.

Yes, there are anecdotal reports, but there also anecdotal reports of it making no difference, and it carries a number of not-insignificant side effects, including affecting cardiac repolarization and glycemic control.

[franky1]

-snip-

Where I am working, almost all patients are being randomized in to a trial. One arm of said trials includes hydroxychloroquine therapy. So there isn't really a medical decision to be made regarding treatment - if they are in the treatment arm they receive it, if they are in any of the other arms, they don't.

Yes, there are anecdotal reports, but there also anecdotal reports of it making no difference, and it carries a number of not-insignificant side effects, including affecting cardiac repolarization and glycemic control.

are they including patients in the 'atrisk' group like pregnant, heart issues, diabetic.

i only ask because i have relatives with heart/diabetic issues and if(small if) they did get severe symptoms of respiratory distress from corona and need treatment where these 'trials' are used more fluidly. would doctors be sensible to decline them out of these 'trials' and give other treatments instead. or is it just random selection

[o_e_l_e_o]

The trials with which I am involved all have their own exclusion criteria. Pregnancy is an exclusion for them all. Very severe comorbidities, especially heart disease, is usually a contraindication, but as these patients are not being admitted to intensive care anyway, we have not (to my knowledge) excluded anyone at our center for that reason. Patients or next of kin can choose to opt out of being included in a trial if they wish.

As I am working largely in the emergency department and intensive care, I can't speak for trials in less severe cases.

[bitbollo]

are they including patients in the 'atrisk' group like pregnant, heart issues, diabetic.
....

you can search by yourself https://clinicaltrials.gov/

I made for you a selection HQC:
https://clinicaltrials.gov/ct2/results?term=hydroxychloroquine&recrs=adfm&type=Intr&cond=%22Respiratory+Tract+Infections%22&phase=12
[hydroxychloroquine | Recruiting, Active, not recruiting, Enrolling by invitation, Unknown status Studies | Interventional Studies | "Respiratory Tract Infections" | Phase 2, 3]

https://clinicaltrials.gov/ct2/results?term=hydroxychloroquine&recrs=adfm&type=Intr&cond=%22Severe+Acute+Respiratory+Syndrome%22&phase=12
[hydroxychloroquine | Recruiting, Active, not recruiting, Enrolling by invitation, Unknown status Studies | Interventional Studies | "Severe Acute Respiratory Syndrome" | Phase 2, 3]

https://clinicaltrials.gov/ct2/results?term=hydroxychloroquine&recrs=adfm&type=Intr&cond=%22Coronavirus+Infections%22&phase=12
[hydroxychloroquine | Recruiting, Active, not recruiting, Enrolling by invitation, Unknown status Studies | Interventional Studies | "Coronavirus Infections" | Phase 2, 3]

Check exclusion criteria of each trial listed,  related hearth issues (?), normally protocol specify very well what are these "heart issues", or you find a generic phrase like:
"Any disorder, unwillingness or inability, not covered by any of the other exclusion criteria, which in the investigator's opinion, might jeopardise the subject's compliance with the extension of the trial"
Find below some exclusions  examples (taken from links):
 
Patients with long QT syndrome or severe ventricular arrhythmias;
Patients using drugs that prolong the QT interval;
Patients with retinopathy or macular degeneration; (these can be diabetics but I haven't find a specific exclusion for diabetic patients).
Use of medications that are contraindicated with hydroxychloroquine: citalopram, escitalopram, hydroxyzine, domperidone, pipéraquine;

[franky1]

i didnt mean the people with heart disease symptoms being the cause of their hospitalisation. i meant the ones in there for corona symptoms but just happen to have other issues previously

also i was thinking more about the relaxed policies some hospitals have been given that doctors can administer it as not an official trial but just another tool in a doctors toolbox for those they feel need it. an unofficial 'trial' to cover them legally to try it
which many countries have as the legal loophole

im guessing by your answers your hospital is just sticking to treatment for only official trial enrolled patients..

EDIT
to answer below.. to save spamming this topic
im not getting into a grammar nazi/dick measuring contest to disrupt the topic
i was asking o e le o a question. so no point talking to someone else who just jumps into the question

im not interested in getting into the legality of the buzzwording of usage outside of an official trial.
thats why in the first post i just said 'trial' with semi quotes around.
i was trying to be subtle
im not interested in the legal buzzwording conversation.

my point was just because there is news that patients who are not official trial enrolled are getting it..
call it therapeutic, compassionate, hailmary, last ditch (not the point in grammar naziing the buzzword that makes it allowed)


but as i said. it seems o e l e o's hospital seems to be just using it only on trial enrolled patients. thus the scope of pro-con use for patient with other issues wont really be studied as much if they are not getting it.. thus i accept o e l e o wont have experience of it.

next edit:
seems he really wants to get into a grammar dick measuring exercise (facepalm)
the actual ettiquite for asking a question to someone is not an @ sign.. thats never been a thing on this forum
instead quoting someone and then asking them a question. makes it relevant to the person in the quote

and if you did not realise it. but in places like spain its shown on polls that 70% of doctors has given it to patients.
yet we dont see thousands of official trials.. simple maths.. basic logic conclusion. its given outside of official trials

anyway o e l e o gave me a satisfactory answer.. so just end your grammar nazi drama

[bitbollo]

i didnt mean the people with heart disease symptoms being the cause of their hospitalisation. i meant the ones in there for corona symptoms but just happen to have other issues previously
...

Dear @franky1 yes It was clear that you were not talking about "heart disease symptoms being the cause of their hospitalisation" but related pre-exiting condition.
Check my previous post, there are few examples.

...
 unofficial 'trial'
...

I don't know what you mean by 'unofficial trial' (maybe are you referring to compassionate use? or off label ? really I have no idea ...) since according GCP/ICH/ any law of any Country, no one will never run an "unofficial trial".

Otherwise something like this will no have any value (nor legally not scientific)... Plus if some one will run something like this can risk a lot of legal implications, fine, license trashed...


EDIT:
Dear @franky1 replying to your edit above, next time use @username when you made a question to some one, since anyone could reply/answer to a question.

Legality of "trial" is the basic of a trial!  
If you don't know what we are talking about, try to check what is an IRB/IEC or read GCP:  this is literally the basic of any trial.

"patients who are not official trial enrolled are getting it."

EH?

of pro-con use for patient with other issues wont really be studied as much if they are not getting it..

I posted a search that I made for you, thanks for ignore it.
As I have already explained if these patients are not EXCLUDED by a protocol/medical judgement they can be included in any trial.