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.

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[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