6 ms·

Expanded access programs for Remdesivir

128 points by mudil 7y ago

wiredone 7y ago
...I’ve seen the movie “I am Legend”. Let’s hope we all get out of Manhattan before this all kicks off.
- Papirola 7y ago
  is this Reddit ?
cm2187 7y ago
Stupid question in case anyone here has a medical background. I was under the impression that covid19 was a two step process. First the virus infects and attacks the protective layer of the lungs (causing cough and fever). Then, the damage done to the protective layer of the lungs results in an infection / pneumonia, and that's where people have respiratory problems and may be in critical condition. But at this stage the viral load is low and the virus isn't the problem anymore, the pneumonia is [1]. This is why I thought Pr Raoult was advocating for the use of chloroquine in the early days of the disease, combined with prompt testing. But it seems that anti-virals (like the study mentioned in this post and other studies in the US and Europe) are tested on patients in critical phase, i.e. with serious cases of pneumonia. Am I missing something or should we not expect anti-virals to be of much use in those cases, as it is too late, we are not dealing with a virus but with a pneumonia? [1] see this useful video: https://www.youtube.com/watch?v=BtN-goy9VOY https://www.youtube.com/watch?v=BtN-goy9VOY
- DrNuke 7y ago
  It is not a stupid question at all but nobody has a legit answer yet, with so many tentative protocols under way all over the world. Some people recover because of non-standard drugs reducing the most critical effects, some other recover because they get non-standard cocktails at early stage, some other die because prolonged fever leads to multiorgan failure or infections. Gilead is making its part, which is laudable.
- ampdepolymerase 7y ago
  Don't forget side effects. At a lot of the dosages to be useful against COVID-19, the drug itself may become problematic.
- lbeltrame 7y ago
  There's a trial[1] whose objective is to determine if chloroquine is actually useful early on in the infection. With a target sample size of 3000 individuals it would have at least sufficient numbers to show if it's actually viable, helps a little, or does not help at all. [1] https://clinicaltrials.gov/ct2/show/NCT04308668?term=hydroxychloroquine&recrs=ab&cond=COVID-19&draw=2 https://clinicaltrials.gov/ct2/show/NCT04308668?term=hydroxy...
  - theologic 7y ago
    I'm also looking forward to this study. Kudos to U of M to get this kicked off quickly. I find it interesting to see how fast they were able to marshal a response. Basically, we go from nothing to something started in 10 days. I've been reflecting on how western culture does not seem as effective as China in suppression of the disease, but the west's ability to do "start up" type activity is amazing, and a place for hope. https://www.twincities.com/2020/03/18/preventing-coronavirus-u-of-m-seeks-1500-volunteers-who-have-been-exposed-to-try-anti-malarial-drug/ https://www.twincities.com/2020/03/18/preventing-coronavirus...
  - brutt 7y ago
    Also,in France: https://www.mediterranee-infection.com/covid-19/ https://www.mediterranee-infection.com/covid-19/
    - tonfa 7y ago
      Tho they've focused mostly on care instead of the science (they don't believe in randomized trials), and it's going to be hard to know if the treatment is efficient from those (the EU and Michigan studies should help figuring that out).
      - vanniv 7y ago
        In the absence of other viable treatments, the efficiency isn't really important. Frankly, if it is only modestly effective, it should still be given to everyone without contraindications. Efficiency only becomes important in a year or two when there are competing therapies. When the choices are Chloroquine or Hopes and Prayers, Chloroquine is the obvious choice (for those that don't have the contraindications, of course -- for those patients, you'd need more evidence to know that the benefits outweighed the risks)
- staplers 7y ago
  If you're in a hospital with others I imagine your viral load could be in constant flux with new patients coming in daily.
  - Enginerrrd 7y ago
    Totally irrelevant, by many, many, orders of magnitude. Like 12-15 orders of magnitude, conservatively.
    - landryraccoon 7y ago
      That sounds like an exaggeration. There are only on the order of 10^13 cells in the entire human body.
      - Enginerrrd 7y ago
        Yeah, ok... but not much of an exaggeration. To use HIV as an example, every infected T cell releases ~50,000 virions when it bursts. So that's ~10^4 times the number of infected cells. So during an infection only 10^9 of your 10^13 cells would need to be infected to get up into the 10^13 range. That's obviously a TINY fraction at 10^9/10^13 = 10^-4. So saying there's trillions of viruses in your body during a major infection like COVID is hardly an exaggeration. 10^15 may or may not be though, in fairness. Compare that to the amount of virus you'd be exposed to in the air though in a COVID ward and its just totally negligible. Unless you're getting injected with virions, it's just not relevant to the progression of your infection when you're already a week into it. I'd be shocked if you could daily environmental viral loads above 10^6. So fine I'll revise it to 6-9 orders of magnitude. The point stands though, it's just not relevant to your immune system compared to the virus it has to deal with from your own cells.
- rjsw 7y ago
  I don't think the seriously ill people have a bacterial lung infection, the reduction in lung effectiveness is directly caused by the virus.
  - cm2187 7y ago
    The video I link in my post seems to suggest otherwise.
- RivieraKid 7y ago
  There's a very interesting hypothesis that lung inflammation is a secondary effect caused by the virus damaging red blood cells, making them unable to transport oxygen. See this thread: https://twitter.com/yishan/status/1244717172871409666 https://twitter.com/yishan/status/1244717172871409666
  - bbojan 7y ago
    What would be the mechanism for damaging the red blood cells, considering that they don't have a nucleus, and therefore the virus cannot replicate in them?
    - raverbashing 7y ago
      The title of the article for those curious is: "COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism"
  - tejtm 7y ago
    TFA https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173 https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surf...
- cadlin 7y ago
  I don't know the answer to the best time to give antivirals, but the lung inflammation happens for some, but not all patients. A non-trivial amount have relatively normal lungs, low oxygen saturation, and an extremely high heartrate. The reasons for this are unknown, but it is an active area of research. Some doctors are beginning to call for treating covid patients like they altitude sickness.[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096066/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096066/
- cwzwarich 7y ago
  > I was under the impression that covid19 was a two step process. First the virus infects and attacks the protective layer of the lungs (causing cough and fever). Then, the damage done to the protective layer of the lungs results in an infection / pneumonia, and that's where people have respiratory problems and may be in critical condition. But at this stage the viral load is low and the virus isn't the problem anymore, the pneumonia is [1]. There are apparently a large number of cases that work differently, with hypoxemia prior to any evidence of severe lung dysfunction: https://www.atsjournals.org/doi/pdf/10.1164/rccm.202003-0817LE https://www.atsjournals.org/doi/pdf/10.1164/rccm.202003-0817... There are also discussions of this phenomenon on Twitter by emergency medicine professionals from NYC, e.g. https://twitter.com/ericleemd/status/1243613497243639809 https://twitter.com/ericleemd/status/1243613497243639809 Some of them propose that early mechanical ventilation in these patients can actually cause lung damage.
  - vanniv 7y ago
    Yeah, in the last two days there is increasing evidence that there's something else going on in at least some patients beyond "pneumonia resulting in ARDS" That tweet is interesting. Some folks are starting the theorize that many of the pneumonia (especially, bilateral) diagnoses based on CXR might be mistaken. The most interesting hypothesis I have encountered (way too little evidence yet to do anything but study it) is that the virus is directly interfering with haemoglobin saturation, and that the abnormal CXR is actually looking at tissue damage caused by haemoglobin degradation somewhat akin to that found in Malaria patients. That hypothesis intends to explain the apparent efficacy of chloroquine, magnified when taken by patients early in the disease, by hypothesizing a similar mechanism of action in COVID as in Malaria -- not by being antiviral, but by inhibiting heme polymerase. The apparent antiviral properties of the treatment are then merely keeping the patient healthy and lung-damage-free while the immune system does its thing. If that were true, then treating COVID patients for pneumonia could be highly counterproductive. Of course, even if the hypothesis is correct, there might be some COVID patients who do develop a bacterial secondary pneumonia -- that is an uncommon-but-not-rare complication of all respiratory illnesses. That might also explain why Azithromycin seems to make Chloroquine more effective -- each drug helping a different subset of patients, rather than actually as a combined effect. As I say, though, there is nowhere near enough evidence yet for this hypothesis -- but it is pretty interesting. It is probably worth a study or two to evaluate. It is a neat hypothesis in that it takes a wide variety of disparate and otherwise apparently contradictory datapoints from clinical experience and weaves them together into a coherent narrative. Of course, that it makes a good narrative is in no way evidence for it's truth, no matter how much we humans love good narratives.
- ericjang 7y ago
  It's not super clear yet what the mechanism of Chloroquine (and derivatives like HCQ) is in combating COVID-19 / Coronavirus, and I imagine people are not sure about Remdesivir either, except that it was previously developed as an Ebola treatment (ineffective), but also shown to be effective in some in vitro studies on SARS-COV-1. Disclaimer: I'm not a doctor or an expert. Chloroquine is suspected to have general prophylactic abilities (like Remdesivir), but also hypothesized that if taken with Zinc, [1] acts as an ionophore with which Zn2+ ions can inactivate the first part of the viral replication step. But at this time, clinical trials for HCQ have been somewhat mixed, with small N-size studies reporting weak benefits or lack of benefits. I don't know of any RCTs that include Zn2+ in the treatment group along with HCQ. It's still as yet unclear. [1] https://www.youtube.com/watch?v=U7F1cnWup9M https://www.youtube.com/watch?v=U7F1cnWup9M
- droithomme 7y ago
  Right, with this and chloroquine, assuming it works to prevent the virus from binding to ACE2, you'd want it to be in the early stages, before massive damage to the lungs, liver, intestines and brains are done (all of these are targeted by this virus). All other countries that are testing these are giving the drugs to patients in both the early and late stage of the infection. In the US alone, trials are only being done in the very late stage, after permanent damage has been done, and it's less likely to be of much use.
  - HarryHirsch 7y ago
    There is a large-scale clinical trial with 3000 participants (https://clinicaltrials.gov/ct2/show/NCT04308668 https://clinicaltrials.gov/ct2/show/NCT04308668) to see if chloroquine prevents progression to severe disease when given shortly after exposure, because when patients are symptomatic it was proved to be completely useless. There isn't a shortage of participants, and at that scale we'll know soon enough if Trump's wonder drug does something. Probably it won't.
- Enginerrrd 7y ago
  We don't have data to really address this, but it's likely a flawed picture in that it's an uncommon progression even for severe cases. The reasoning is that antibiotics don't seem to be very effective for the most severe cases, and at least anecdotally among physicians, the evidence for secondary infection is usually weak. There seems to be a lot of primary damage caused by the virus itself to the point of diminished lung function. Without getting overly technical, there's also some atypical results in some of the labs that seems to indicate that the virus is just overwhelming parts of their immune system, which are in collapse. This can drive up other parts that are inflammatory in nature leading to the cytokine storm and ARDS which comes on very rapidly. However, the fact that things like steroids are leading to WORSE outcomes suggests that the immune suppression is very unhelpful which suggests the problem is more that tissues are just getting overwhelmed with virus.
  - bardworx 7y ago
    Sorry for the ignorant question but you mentioned steroids and immune suppression. Does that imply that steroids suppress the immune system in some way? I’ve tried googling but came up empty besides a paper on “ glucocorticoids” which seems to be something to do with cortisol shots for reduced inflammation, which has immune suppression tendencies. Is that what you mean? And if yes, is this for all levels of steroids or just some particular types? (IE steroids in an asthma inhaler vs cortisol shot vs anabolic steroids). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047790/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047790/
    - JamesBarney 7y ago
      Corticosteroids suppress the immune system, as do anabolic steroids, but it's not a property inherent to steroids. For instance estrogen is also a steroid and doesn't suppress the immune system.
    - vikramkr 7y ago
      Yep, corticosteroids are used for immune suppression. That's why they're used in autoimmune conditions https://www.mayoclinic.org/steroids/art-20045692 https://www.mayoclinic.org/steroids/art-20045692
- JohnJamesRambo 7y ago
  This is why they combine the chloroquine with a Z pack.
- xkcd-sucks 7y ago
  With untested drugs, the risk-benefit is considered such that only people who are certainly going to die without intervention can be treated without incurring further liability. So only "terminal" cases get remdesivir in the first place.
underdeserver 7y ago
As with anything pharmaceutical - they still need to make sure it doesn't have long term side effects. As horrible as it is to prevent treatment and prolong suffering, it would be more horrible if thousands of people suffer from unknown side effects if they would have recovered without it.
- cm2187 7y ago
  So you advocate to not use any new molecule until we have studied the effects over 5-10 years?
  - QUFB 7y ago
    False dichotomy much? This is a nuanced issue, and the parent comment didn't suggest this at all.
    - cm2187 7y ago
      Well, how do you know the long term effects if you don't study the effects over a long period?
  - underdeserver 7y ago
    I advocate clinical trials and giving it to those would surely die without it. Which is what the FDA prescribes, and what Gilead is doing. Nobody said the studies should take 5-10 years. Obviously this should be weighted against the urgency.
- bardworx 7y ago
  My takeaway that this drug was for folks that are literally on their “last leg”. I don’t think potential aide effects are going to deter such a patient, at least it wouldn’t deter myself. It’s tough to worry about a future when you don’t have one.
  - sudosysgen 7y ago
    Only for now, because it isn't approved. If it is approved and doesn't have too many effects it should be much much more effective early on.
daenz 7y ago
>The safety and efficacy are not yet known so while we feel the greatest sense of urgency in our work with remdesivir, we must take the responsible, ethical approach of determining whether it is indeed a safe, effective treatment. >we continue to provide remdesivir on an individual compassionate use basis for children and pregnant women. Can someone explain this logic to me? The safety and efficacy is not known, so we're going to give it to the most vulnerable people first?
- ISL 7y ago
  If someone is going to die anyway, a research drug that might save them sounds pretty awesome.
  - deleted 7y ago
    [deleted]
  - Waterluvian 7y ago
    But children are of least concern. Or do they mean children who are going to die? How many instances of that are there? And pregnant women? That's hard to reconcile with common sense.
    - dpbriggs 7y ago
      Are you unaware that judgement will be used? Compassionate uses are hail marys and are used appropriately.
  - kayfox 7y ago
    Some more info on Compassionate Use: https://www.cancer.org/treatment/treatments-and-side-effects/clinical-trials/compassionate-drug-use.html https://www.cancer.org/treatment/treatments-and-side-effects...
- solotronics 7y ago
  It works but they don't have enough for everyone.
- 7y ago
baxtr 7y ago
> Remdesivir is still an investigational medicine and has not been approved by regulatory authorities anywhere in the world. The safety and efficacy are not yet known so while we feel the greatest sense of urgency in our work with remdesivir, we must take the responsible, ethical approach of determining whether it is indeed a safe, effective treatment. This is why multiple clinical trials for remdesivir are underway, involving thousands of patients with COVID-19 across the world.
Tepix 7y ago
Gilead is providing the entirety of this existing supply at no cost, to treat patients with the most severe symptoms of COVID-19. The 1.5 million individual doses are available for compassionate use, expanded access and clinical trials and will be donated for broader distribution following any potential future regulatory authorizations. These doses are for treating patients with severe symptoms, through daily intravenous infusions in a hospital setting. Having a potential treatment in our hands comes with significant responsibility. Providing our existing supplies at no charge is the right thing to do, to facilitate access to patients as quickly as possible and in recognition of the public emergency posed by this pandemic. I'm glad to hear this!
aluminussoma 7y ago
Remdesivir was one of the earliest promising candidates to treat covid-19 since it had promising results - in the lab - against other coronaviruses like SARS and MERS. It did not have results in humans because those viruses went away before in vivo testing could be performed. Will it work? If it was a runaway success, I would have expected any of the current clinical trials to be cut short as the difference between placebo and non-placebo patients would have been obvious. That hadn't happened. I'm still hoping it has some positive effect. The drug also had to administered through an IV over several days. It is not a pill you take. If it works, this makes treatment a little bit more difficult. You can't just give patients a pill and send them home.
RivieraKid 7y ago
It's surprising and disappointing that production takes 6 months, that's well beyond the peak of the pandemic.
- dehrmann 7y ago
  Get ready for conscripted US manufacturing delivering ventilators a month after they're needed.
- BryanBigs 7y ago
  Of this wave of the pandemic. Might be right in time for wave 2.
- benchtobedside 7y ago
  See this recent article on HN that addresses how difficult it is to synthesize: https://www.acsh.org/news/2020/03/26/problem-remdesivir-making-it-14665 https://www.acsh.org/news/2020/03/26/problem-remdesivir-maki...
DominikPeters 7y ago
I’m not too glad. From the description, it sounds like it’s a massive expense to produce the drug, and if public attitudes force companies to give the results away for free, then there is no expectation of profits for pharma companies to invest for future preparedness for pandemics. I’d like them to charge a lot and make a killing. Governments can subsidize if they want.
- mr_isomies 7y ago
  How is "public attitude" forcing the company?
- a_t48 7y ago
  Why don't we just get the drugs now and figure out payment when there isn't an emergency going on? When there's a potential for thousands of people dying, I'd rather get the medicine produced and in the hands of the people who need it immediately. I agree that if the drug helps they should be compensated well, but there's a time and place for everything.
- ianmobbs 7y ago
  That's fairly cruel of you.
- dwaltrip 7y ago
  Perhaps pharma companies shouldn't be the ones planning for pandemic preparedness? Maybe some sort of societal structure that operates at a level above individual companies could bear this responsibility. That being said, I think it is fine if the government buys these supplies. I also think it is fine if a company wants to donate.
- basilgohar 7y ago
  You should be glad. Pharma companies are well-known historically to have milked monopolies to their own financial favor at the cost of public health, well-being, and welfare. They are not traditionally seen nor acting in congruence with altruism. If a company has decided to do so, that is great. But I think seeing this as some sort of a slippery slope seems completely backwards to me. It's about time pharma companies cut a little of their profits for the benefit of people. The cost of research is far outweighed by their excessive profits that come after the fact.
ltbarcly3 7y ago
There are a ton of studies ongoing, stock pumping PR campaigns like this aren't responsible until the data is in, and there should be studies breaking their blinds this week. It's fine to ramp up production just in case, but that hardly justifies a press release by the CEO.
sadfev 7y ago
Didn’t the Japanese rule this drug out saying it’s totally ineffective?

128 points by mudil 7y ago

wiredone 7y ago

...I’ve seen the movie “I am Legend”. Let’s hope we all get out of Manhattan before this all kicks off.

Papirola 7y ago
is this Reddit ?

cm2187 7y ago

Stupid question in case anyone here has a medical background. I was under the impression that covid19 was a two step process. First the virus infects and attacks the protective layer of the lungs (causing cough and fever). Then, the damage done to the protective layer of the lungs results in an infection / pneumonia, and that's where people have respiratory problems and may be in critical condition. But at this stage the viral load is low and the virus isn't the problem anymore, the pneumonia is [1]. This is why I thought Pr Raoult was advocating for the use of chloroquine in the early days of the disease, combined with prompt testing. But it seems that anti-virals (like the study mentioned in this post and other studies in the US and Europe) are tested on patients in critical phase, i.e. with serious cases of pneumonia. Am I missing something or should we not expect anti-virals to be of much use in those cases, as it is too late, we are not dealing with a virus but with a pneumonia? [1] see this useful video: https://www.youtube.com/watch?v=BtN-goy9VOY https://www.youtube.com/watch?v=BtN-goy9VOY

DrNuke 7y ago
It is not a stupid question at all but nobody has a legit answer yet, with so many tentative protocols under way all over the world. Some people recover because of non-standard drugs reducing the most critical effects, some other recover because they get non-standard cocktails at early stage, some other die because prolonged fever leads to multiorgan failure or infections. Gilead is making its part, which is laudable.
ampdepolymerase 7y ago
Don't forget side effects. At a lot of the dosages to be useful against COVID-19, the drug itself may become problematic.
lbeltrame 7y ago
There's a trial[1] whose objective is to determine if chloroquine is actually useful early on in the infection. With a target sample size of 3000 individuals it would have at least sufficient numbers to show if it's actually viable, helps a little, or does not help at all. [1] https://clinicaltrials.gov/ct2/show/NCT04308668?term=hydroxychloroquine&recrs=ab&cond=COVID-19&draw=2 https://clinicaltrials.gov/ct2/show/NCT04308668?term=hydroxy...
- theologic 7y ago
  I'm also looking forward to this study. Kudos to U of M to get this kicked off quickly. I find it interesting to see how fast they were able to marshal a response. Basically, we go from nothing to something started in 10 days. I've been reflecting on how western culture does not seem as effective as China in suppression of the disease, but the west's ability to do "start up" type activity is amazing, and a place for hope. https://www.twincities.com/2020/03/18/preventing-coronavirus-u-of-m-seeks-1500-volunteers-who-have-been-exposed-to-try-anti-malarial-drug/ https://www.twincities.com/2020/03/18/preventing-coronavirus...
- brutt 7y ago
  Also,in France: https://www.mediterranee-infection.com/covid-19/ https://www.mediterranee-infection.com/covid-19/
  - tonfa 7y ago
    Tho they've focused mostly on care instead of the science (they don't believe in randomized trials), and it's going to be hard to know if the treatment is efficient from those (the EU and Michigan studies should help figuring that out).
    - vanniv 7y ago
      In the absence of other viable treatments, the efficiency isn't really important. Frankly, if it is only modestly effective, it should still be given to everyone without contraindications. Efficiency only becomes important in a year or two when there are competing therapies. When the choices are Chloroquine or Hopes and Prayers, Chloroquine is the obvious choice (for those that don't have the contraindications, of course -- for those patients, you'd need more evidence to know that the benefits outweighed the risks)
staplers 7y ago
If you're in a hospital with others I imagine your viral load could be in constant flux with new patients coming in daily.
- Enginerrrd 7y ago
  Totally irrelevant, by many, many, orders of magnitude. Like 12-15 orders of magnitude, conservatively.
  - landryraccoon 7y ago
    That sounds like an exaggeration. There are only on the order of 10^13 cells in the entire human body.
    - Enginerrrd 7y ago
      Yeah, ok... but not much of an exaggeration. To use HIV as an example, every infected T cell releases ~50,000 virions when it bursts. So that's ~10^4 times the number of infected cells. So during an infection only 10^9 of your 10^13 cells would need to be infected to get up into the 10^13 range. That's obviously a TINY fraction at 10^9/10^13 = 10^-4. So saying there's trillions of viruses in your body during a major infection like COVID is hardly an exaggeration. 10^15 may or may not be though, in fairness. Compare that to the amount of virus you'd be exposed to in the air though in a COVID ward and its just totally negligible. Unless you're getting injected with virions, it's just not relevant to the progression of your infection when you're already a week into it. I'd be shocked if you could daily environmental viral loads above 10^6. So fine I'll revise it to 6-9 orders of magnitude. The point stands though, it's just not relevant to your immune system compared to the virus it has to deal with from your own cells.
rjsw 7y ago
I don't think the seriously ill people have a bacterial lung infection, the reduction in lung effectiveness is directly caused by the virus.
- cm2187 7y ago
  The video I link in my post seems to suggest otherwise.
RivieraKid 7y ago
There's a very interesting hypothesis that lung inflammation is a secondary effect caused by the virus damaging red blood cells, making them unable to transport oxygen. See this thread: https://twitter.com/yishan/status/1244717172871409666 https://twitter.com/yishan/status/1244717172871409666
- bbojan 7y ago
  What would be the mechanism for damaging the red blood cells, considering that they don't have a nucleus, and therefore the virus cannot replicate in them?
  - raverbashing 7y ago
    The title of the article for those curious is: "COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism"
- tejtm 7y ago
  TFA https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173 https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surf...
cadlin 7y ago
I don't know the answer to the best time to give antivirals, but the lung inflammation happens for some, but not all patients. A non-trivial amount have relatively normal lungs, low oxygen saturation, and an extremely high heartrate. The reasons for this are unknown, but it is an active area of research. Some doctors are beginning to call for treating covid patients like they altitude sickness.[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096066/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096066/
cwzwarich 7y ago
> I was under the impression that covid19 was a two step process. First the virus infects and attacks the protective layer of the lungs (causing cough and fever). Then, the damage done to the protective layer of the lungs results in an infection / pneumonia, and that's where people have respiratory problems and may be in critical condition. But at this stage the viral load is low and the virus isn't the problem anymore, the pneumonia is [1]. There are apparently a large number of cases that work differently, with hypoxemia prior to any evidence of severe lung dysfunction: https://www.atsjournals.org/doi/pdf/10.1164/rccm.202003-0817LE https://www.atsjournals.org/doi/pdf/10.1164/rccm.202003-0817... There are also discussions of this phenomenon on Twitter by emergency medicine professionals from NYC, e.g. https://twitter.com/ericleemd/status/1243613497243639809 https://twitter.com/ericleemd/status/1243613497243639809 Some of them propose that early mechanical ventilation in these patients can actually cause lung damage.
- vanniv 7y ago
  Yeah, in the last two days there is increasing evidence that there's something else going on in at least some patients beyond "pneumonia resulting in ARDS" That tweet is interesting. Some folks are starting the theorize that many of the pneumonia (especially, bilateral) diagnoses based on CXR might be mistaken. The most interesting hypothesis I have encountered (way too little evidence yet to do anything but study it) is that the virus is directly interfering with haemoglobin saturation, and that the abnormal CXR is actually looking at tissue damage caused by haemoglobin degradation somewhat akin to that found in Malaria patients. That hypothesis intends to explain the apparent efficacy of chloroquine, magnified when taken by patients early in the disease, by hypothesizing a similar mechanism of action in COVID as in Malaria -- not by being antiviral, but by inhibiting heme polymerase. The apparent antiviral properties of the treatment are then merely keeping the patient healthy and lung-damage-free while the immune system does its thing. If that were true, then treating COVID patients for pneumonia could be highly counterproductive. Of course, even if the hypothesis is correct, there might be some COVID patients who do develop a bacterial secondary pneumonia -- that is an uncommon-but-not-rare complication of all respiratory illnesses. That might also explain why Azithromycin seems to make Chloroquine more effective -- each drug helping a different subset of patients, rather than actually as a combined effect. As I say, though, there is nowhere near enough evidence yet for this hypothesis -- but it is pretty interesting. It is probably worth a study or two to evaluate. It is a neat hypothesis in that it takes a wide variety of disparate and otherwise apparently contradictory datapoints from clinical experience and weaves them together into a coherent narrative. Of course, that it makes a good narrative is in no way evidence for it's truth, no matter how much we humans love good narratives.
ericjang 7y ago
It's not super clear yet what the mechanism of Chloroquine (and derivatives like HCQ) is in combating COVID-19 / Coronavirus, and I imagine people are not sure about Remdesivir either, except that it was previously developed as an Ebola treatment (ineffective), but also shown to be effective in some in vitro studies on SARS-COV-1. Disclaimer: I'm not a doctor or an expert. Chloroquine is suspected to have general prophylactic abilities (like Remdesivir), but also hypothesized that if taken with Zinc, [1] acts as an ionophore with which Zn2+ ions can inactivate the first part of the viral replication step. But at this time, clinical trials for HCQ have been somewhat mixed, with small N-size studies reporting weak benefits or lack of benefits. I don't know of any RCTs that include Zn2+ in the treatment group along with HCQ. It's still as yet unclear. [1] https://www.youtube.com/watch?v=U7F1cnWup9M https://www.youtube.com/watch?v=U7F1cnWup9M
droithomme 7y ago
Right, with this and chloroquine, assuming it works to prevent the virus from binding to ACE2, you'd want it to be in the early stages, before massive damage to the lungs, liver, intestines and brains are done (all of these are targeted by this virus). All other countries that are testing these are giving the drugs to patients in both the early and late stage of the infection. In the US alone, trials are only being done in the very late stage, after permanent damage has been done, and it's less likely to be of much use.
- HarryHirsch 7y ago
  There is a large-scale clinical trial with 3000 participants (https://clinicaltrials.gov/ct2/show/NCT04308668 https://clinicaltrials.gov/ct2/show/NCT04308668) to see if chloroquine prevents progression to severe disease when given shortly after exposure, because when patients are symptomatic it was proved to be completely useless. There isn't a shortage of participants, and at that scale we'll know soon enough if Trump's wonder drug does something. Probably it won't.
Enginerrrd 7y ago
We don't have data to really address this, but it's likely a flawed picture in that it's an uncommon progression even for severe cases. The reasoning is that antibiotics don't seem to be very effective for the most severe cases, and at least anecdotally among physicians, the evidence for secondary infection is usually weak. There seems to be a lot of primary damage caused by the virus itself to the point of diminished lung function. Without getting overly technical, there's also some atypical results in some of the labs that seems to indicate that the virus is just overwhelming parts of their immune system, which are in collapse. This can drive up other parts that are inflammatory in nature leading to the cytokine storm and ARDS which comes on very rapidly. However, the fact that things like steroids are leading to WORSE outcomes suggests that the immune suppression is very unhelpful which suggests the problem is more that tissues are just getting overwhelmed with virus.
- bardworx 7y ago
  Sorry for the ignorant question but you mentioned steroids and immune suppression. Does that imply that steroids suppress the immune system in some way? I’ve tried googling but came up empty besides a paper on “ glucocorticoids” which seems to be something to do with cortisol shots for reduced inflammation, which has immune suppression tendencies. Is that what you mean? And if yes, is this for all levels of steroids or just some particular types? (IE steroids in an asthma inhaler vs cortisol shot vs anabolic steroids). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047790/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047790/
  - JamesBarney 7y ago
    Corticosteroids suppress the immune system, as do anabolic steroids, but it's not a property inherent to steroids. For instance estrogen is also a steroid and doesn't suppress the immune system.
  - vikramkr 7y ago
    Yep, corticosteroids are used for immune suppression. That's why they're used in autoimmune conditions https://www.mayoclinic.org/steroids/art-20045692 https://www.mayoclinic.org/steroids/art-20045692
JohnJamesRambo 7y ago
This is why they combine the chloroquine with a Z pack.
xkcd-sucks 7y ago
With untested drugs, the risk-benefit is considered such that only people who are certainly going to die without intervention can be treated without incurring further liability. So only "terminal" cases get remdesivir in the first place.

underdeserver 7y ago

As with anything pharmaceutical - they still need to make sure it doesn't have long term side effects. As horrible as it is to prevent treatment and prolong suffering, it would be more horrible if thousands of people suffer from unknown side effects if they would have recovered without it.

cm2187 7y ago
So you advocate to not use any new molecule until we have studied the effects over 5-10 years?
- QUFB 7y ago
  False dichotomy much? This is a nuanced issue, and the parent comment didn't suggest this at all.
  - cm2187 7y ago
    Well, how do you know the long term effects if you don't study the effects over a long period?
- underdeserver 7y ago
  I advocate clinical trials and giving it to those would surely die without it. Which is what the FDA prescribes, and what Gilead is doing. Nobody said the studies should take 5-10 years. Obviously this should be weighted against the urgency.
bardworx 7y ago
My takeaway that this drug was for folks that are literally on their “last leg”. I don’t think potential aide effects are going to deter such a patient, at least it wouldn’t deter myself. It’s tough to worry about a future when you don’t have one.
- sudosysgen 7y ago
  Only for now, because it isn't approved. If it is approved and doesn't have too many effects it should be much much more effective early on.

daenz 7y ago

>The safety and efficacy are not yet known so while we feel the greatest sense of urgency in our work with remdesivir, we must take the responsible, ethical approach of determining whether it is indeed a safe, effective treatment. >we continue to provide remdesivir on an individual compassionate use basis for children and pregnant women. Can someone explain this logic to me? The safety and efficacy is not known, so we're going to give it to the most vulnerable people first?

ISL 7y ago
If someone is going to die anyway, a research drug that might save them sounds pretty awesome.
- deleted 7y ago
  [deleted]
- Waterluvian 7y ago
  But children are of least concern. Or do they mean children who are going to die? How many instances of that are there? And pregnant women? That's hard to reconcile with common sense.
  - dpbriggs 7y ago
    Are you unaware that judgement will be used? Compassionate uses are hail marys and are used appropriately.
- kayfox 7y ago
  Some more info on Compassionate Use: https://www.cancer.org/treatment/treatments-and-side-effects/clinical-trials/compassionate-drug-use.html https://www.cancer.org/treatment/treatments-and-side-effects...
solotronics 7y ago
It works but they don't have enough for everyone.
7y ago

baxtr 7y ago

> Remdesivir is still an investigational medicine and has not been approved by regulatory authorities anywhere in the world. The safety and efficacy are not yet known so while we feel the greatest sense of urgency in our work with remdesivir, we must take the responsible, ethical approach of determining whether it is indeed a safe, effective treatment. This is why multiple clinical trials for remdesivir are underway, involving thousands of patients with COVID-19 across the world.

Tepix 7y ago

Gilead is providing the entirety of this existing supply at no cost, to treat patients with the most severe symptoms of COVID-19. The 1.5 million individual doses are available for compassionate use, expanded access and clinical trials and will be donated for broader distribution following any potential future regulatory authorizations. These doses are for treating patients with severe symptoms, through daily intravenous infusions in a hospital setting. Having a potential treatment in our hands comes with significant responsibility. Providing our existing supplies at no charge is the right thing to do, to facilitate access to patients as quickly as possible and in recognition of the public emergency posed by this pandemic. I'm glad to hear this!

aluminussoma 7y ago

Remdesivir was one of the earliest promising candidates to treat covid-19 since it had promising results - in the lab - against other coronaviruses like SARS and MERS. It did not have results in humans because those viruses went away before in vivo testing could be performed. Will it work? If it was a runaway success, I would have expected any of the current clinical trials to be cut short as the difference between placebo and non-placebo patients would have been obvious. That hadn't happened. I'm still hoping it has some positive effect. The drug also had to administered through an IV over several days. It is not a pill you take. If it works, this makes treatment a little bit more difficult. You can't just give patients a pill and send them home.

RivieraKid 7y ago

It's surprising and disappointing that production takes 6 months, that's well beyond the peak of the pandemic.

dehrmann 7y ago
Get ready for conscripted US manufacturing delivering ventilators a month after they're needed.
BryanBigs 7y ago
Of this wave of the pandemic. Might be right in time for wave 2.
benchtobedside 7y ago
See this recent article on HN that addresses how difficult it is to synthesize: https://www.acsh.org/news/2020/03/26/problem-remdesivir-making-it-14665 https://www.acsh.org/news/2020/03/26/problem-remdesivir-maki...

DominikPeters 7y ago

I’m not too glad. From the description, it sounds like it’s a massive expense to produce the drug, and if public attitudes force companies to give the results away for free, then there is no expectation of profits for pharma companies to invest for future preparedness for pandemics. I’d like them to charge a lot and make a killing. Governments can subsidize if they want.

mr_isomies 7y ago
How is "public attitude" forcing the company?
a_t48 7y ago
Why don't we just get the drugs now and figure out payment when there isn't an emergency going on? When there's a potential for thousands of people dying, I'd rather get the medicine produced and in the hands of the people who need it immediately. I agree that if the drug helps they should be compensated well, but there's a time and place for everything.
ianmobbs 7y ago
That's fairly cruel of you.
dwaltrip 7y ago
Perhaps pharma companies shouldn't be the ones planning for pandemic preparedness? Maybe some sort of societal structure that operates at a level above individual companies could bear this responsibility. That being said, I think it is fine if the government buys these supplies. I also think it is fine if a company wants to donate.
basilgohar 7y ago
You should be glad. Pharma companies are well-known historically to have milked monopolies to their own financial favor at the cost of public health, well-being, and welfare. They are not traditionally seen nor acting in congruence with altruism. If a company has decided to do so, that is great. But I think seeing this as some sort of a slippery slope seems completely backwards to me. It's about time pharma companies cut a little of their profits for the benefit of people. The cost of research is far outweighed by their excessive profits that come after the fact.

ltbarcly3 7y ago

There are a ton of studies ongoing, stock pumping PR campaigns like this aren't responsible until the data is in, and there should be studies breaking their blinds this week. It's fine to ramp up production just in case, but that hardly justifies a press release by the CEO.

sadfev 7y ago

Didn’t the Japanese rule this drug out saying it’s totally ineffective?