13 ms·

Study: Severe Covid-19 Cases Don't Respond to Hydroxychloroquine+Azithromycin

123 points by aazaa 7y ago

uncoder0 7y ago
I am not in any way qualified in the medical domain but these methods look similar to the other Study that was viewed as flawed that showed it did work. Seems there is no solid data either way.
- archgoon 7y ago
  Which, in itself, is probably a valuable take-away.
- arrrg 7y ago
  These studies tell me mostly that if there is an effect it’s probably not a large one.
- malpighien 7y ago
  Well this one seems more rigorous. They monitored concentration in blood for 4 days, they checked viral presence two following days at the end. They don't mention viral load though and I don't know if they have a threshold for cycles in QPCR to estimate that. This kind of paper is not here to say here is the proof it works or it does not work, it is meant to say: this what we had with us, this how we did it, this is the results we observed and whether or not it validates the hypothesis stated.
sdiq 7y ago
https://abc7news.com/amp/coronavirus-drug-covid-19-malaria-hydroxychloroquine/6079864/ https://abc7news.com/amp/coronavirus-drug-covid-19-malaria-h... Not a study but just another anecdote. Using zinc this time round rather than azithromycin.
- snapetom 7y ago
  Yeah, I don't know what's the point of these studies that don't look at HCQ+zinc when the hypothesis is that HCQ promotes zinc absorption.
  - HarryHirsch 7y ago
    The hypothesis is that hydroxychloroquin interferes with glycosylation of cell surface proteins that are essential for entry of the virus into the cell. The zinc notion is total bunk, intracellular zinc concentration is tightly controlled. Random zinc excursions just don't happen, if they did they would result in death.
    - podgaj 7y ago
      This is so wrong I do not know where to start. ADAM17 is responsible for shedding of ACE2 from the cell which creates soluble ACE2. If ACE2 is not ON the cell the virus cannot infect the cell. ADAM17, like ACE2 is a zinc finger protein and uses zinc as a cofactor. Also, zinc is widely understood to lower the immune response by affecting interferon levels. It is not only about intracellular zinc. But in a deficiency intracellular zinc has even less chance of being brought into the cell, right? To say that zinc does not matter because hydroxychloroquin is absurd.
    - giardini 7y ago
      HarryHirsch says "The zinc notion is total bunk..." I am unclear what you mean here but this in-vitro experiment. which studied interaction of zinc ions with chloroquine in a human ovarian cancer cell line. shows far more zinc entering cells that are exposed to chloroquine: "Chloroquine Is a Zinc Ionophore": https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/
  - pengaru 7y ago
    Isn't there always going to be some ambient zinc available even without additional supplementing? I imagine there'd be some evidence of efficacy regardless, but this is nowhere near my area of expertise.
- klipt 7y ago
  I hate the way this drug has been politicized by Trump yapping it up before there were any good studies. Politicians should shut up about unproven medicines and leave it to the professionals to actually practice, you know, evidence based medicine.
  - betterunix2 7y ago
    "Politicians should shut up and leave it to the professionals" FTFY.
    - giardini 7y ago
      A political leader's role is not to choose medications but to give people hope and to keep the wheels of society rolling. But no matter what, there will always be more questions about what will be done. I think Trump was sufficiently vague yet optimistic in his answers, as befits his role. Consider how different it would have been had he said "We know of nothing that works against this virus." or even worse, "We're screwed! Go home and tell your children we're all gonna die!".
sna1l 7y ago
n = 11?
- michael_storm 7y ago
  Believe it or not, it's pretty hard to conduct a large-scale study in the middle of the largest pandemic in modern history.
  - rattray 7y ago
    Why is that?
  - monadic2 7y ago
    I'd estimate they were commenting on the quality of the results, not critiquing the personal efforts of the researchers.
  - SpicyLemonZest 7y ago
    I don’t believe it. Studying how to effectively treat coronavirus patients is literally the most important problem in the world right now, and I’m sure a lot more than 11 severe cases are being treated with hydrochloroquine.
    - kilbuz 7y ago
      While your point is a good one, meaningful clinical research is hard enough under normal conditions. Forms, enrollment, protocols, data collection, statistical analysis plans, reporting, etc. It's an entire industry used to operating in scales that often span years for a single meaningful study.
      - SpicyLemonZest 7y ago
        And I agree with that as far as it goes, but I think it reflects the problem - clinical research contains a bunch of hurdles that have nothing to do with uncovering the truth. So in a sudden emergency, where clinical research starts to diverge from the treatment decisions of doctors and the drug supply actions of governments, I'm not going to put much weight on clinical research.
trhway 7y ago
[IANAD] hydroxychloroquine is an immunosuppressant and shouldn't be combined even with vaccines ( https://www.medicinenet.com/hydroxychloroquine/article.htm#which_drugs_or_supplements_interact_with_hydroxychloroquine_plaquenil https://www.medicinenet.com/hydroxychloroquine/article.htm#w... ), so using it when immune system is really fighting an infection may happen to be very antiproductive unless it is a case of COVID triggered cytokine storm (hyperinflammation) when such immunosuppressant is probably what you'd really want. May be it is a reason why in come cases of COVID it works and in some doesn't. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6... "However, in hyperinflammation, immunosuppression is likely to be beneficial. Re-analysis of data from a phase 3 randomised controlled trial of IL-1 blockade (anakinra) in sepsis, showed significant survival benefit in patients with hyperinflammation, without increased adverse events.8 A multicentre, randomised controlled trial of tocilizumab (IL-6 receptor blockade, licensed for cytokine release syndrome), has been approved in patients with COVID-19 pneumonia and elevated IL-6 in China " Notable fact is that majority of the deaths of the second wave (the deadliest, which in addition to children/weak/elderly was also strongly hitting healthy 25-35 years old) of Spanish flu was due to cytokine storm.
- orwin 7y ago
  Yes, obviously in case of hyperinflammation doctor are giving immunosuppressing drugs, HCQ or other depending on the stocks (and of course the patient history and other drugs given prior). They are very capable people in most cases, urgentists are often very knowledgable, and reanimation doctors are probably the best at interfering/preventing coktail effect. They are not available in all cases, but they try to be there for the most important ones. No one, no scientist is saying with certainty that HCQ does not work at all. However, the maxim is primum non nocere. Are HCQ effects important enough to use it in every case when you can do otherwise? Well, according to the last Raoult study on 80 mild cases, no. 3 hospitalisation, 1 death for 80 cases is around the same result as German/S.K. mild cases who are given no treatment at all (a bit superior, even, but n=80 is clearly not enough). Maybe HCQ reduce contagiosity. In this case, is HCQ more efficient than interferon? I know that i would prefer interferon as my liver and kidneys can take more hit than my heart atm (i already have a medication that cause tachycardia when i overdose it a little + some minor heart issues). Is HCQ more efficient than rinovir? this particular article seems to say that it's not but why should i trust this article more than Raoult and some French articles? Should i take everything (interferon, rinovir, HCQ, CQ) and hope for the best? Or, since i can afford to as i live in a rich country, should i wait the different study results?
sunsu 7y ago
By the time it's severe, it's often too late: https://twitter.com/yishan/status/1244717172871409666?s=20 https://twitter.com/yishan/status/1244717172871409666?s=20
webmobdev 7y ago
Wonder when the Indian Council of Medical Research will release more papers - there were a few patients who responded positively under their suggested treatment plan: > “We used a combo of Lopinavir and Ritonavir drugs which are usually given as a second line of treatment for HIV with drugs meant for curing malaria and swine flu. We administered this line of treatment to a 70-year-old Italian woman, who had come as a tourist to Rajasthan, who tested positive and was being treated by us, as well as another Italian, who is 69-year-old,” said Dr Sudhir Bhandari. > ... “The team of doctors under the leadership of Dr Sudhir Bhandari, Principal of SMS Medical College held consultations with the ICMR and tried a combination medicines given for malaria, swine flu (Tamiflu) along with drugs for HIV and it worked well. All three persons including the Italians were cured this way,” said Rohit Kumar Singh, additional chief secretary, health of Rajasthan government. Source: https://www.nationalheraldindia.com/india/three-coronavirus-afflicted-patients-recover-due-to-innovative-treatment-by-doctors-at-jaipur-govt-hospital https://www.nationalheraldindia.com/india/three-coronavirus-... > ... The three persons who tested positive were administered a combination of 200mg Lopinavir and 50 mg of Ritonavir twice a day besides Oseltamivir and Chloroquine that are given to the swine flu and malaria patients. > However, the doctors at the SMS Hospital warned that this was only an emergency treatment and the HIV medicines were used only as an emergency measure that could help in regaining normalcy. Source: https://www.nationalheraldindia.com/india/covid-19-magic-medicine-of-jaipurs-hospital-cures-3-patients-draws-attention-in-medical-world https://www.nationalheraldindia.com/india/covid-19-magic-med...
- webmobdev 7y ago
  Update: The Indian Council of Medical Research has also given the go ahead to try out plasma therapy for the really serious, and some hospitals and institute are waiting for clearance of the same from the Drug Controller General of India: > ... Blood for the plasma therapy will be collected from recovered patients at SCTIMST and the medical colleges and donated to critical patients with sanction from Blood Transfusion Council. Plasma would be separated from blood and taken to other hospitals under refrigeration. > ... When a person suffers from COVID-19, antibodies are created in his or her body as defence. Such B lymphocytes would be present in plasma. After a patient recovers from the disease, these antibodies remain in blood to prevent another attack by the virus. The plasma collected from such people and given to another patient would have antibodies which target the virus and prevent the recipient from slipping into a more serious condition. According to researches, plasma taken from one donor would have sufficient doses for two patients. Source: https://english.manoramaonline.com/news/kerala/2020/04/09/kerala-plans-trials-in-convalescent-plasma-therapy-against-covid.html https://english.manoramaonline.com/news/kerala/2020/04/09/ke...
rodgerd 7y ago
So a bunch of people who have medical conditions which actually respond to HCQ have lost access to it, for no benefit to anyone else. Great.
- transreal 7y ago
  Unfortunately, I'm one of those people. My last refill ran out last week, and my pharmacist doesn't think I can get a refill anytime soon :-( Fortunately my condition is not life threatening or severe, but it's something I've been living with for many years, and the HCQ was just finally getting it under control, so it's a bummer that there is so much hoarding going on before we even know if it really works for Covid-19. Also, it is not a risk free medication. While it's generally safe, my doctor makes me get frequent lab work & a vision test because the side effects can be pretty bad for a small minority of people.
rpiguy 7y ago
COVID-19 attacks hemoglobin and that is how it damages the lungs. With your hemoglobin unable to exchange oxygen with blood in the lungs, it causes terrible damage. 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... Chloroquine prevents the virus from affecting hemoglobin, or reduces the effect. This is also how Chloroquine treats malaria. The problem with a study on severe cases is that the damage is already done and the hemoglobin is already compromised. It is best to start treatment with chloroquine prior to reaching the severe stage. By the time you are severe you’ve gotten permanent lung damage and the immune system is in a race condition unable to keep up with the virus. If you want to detour into tinfoil hat territory, you could posit that these studies on severe patients were designed knowing it would show low or no efficacy, because it’s too late to protect the patient’s hemoglobin. Azithromycin slows ribosonal RNA replication in bacteria. It is unclear how it helps with a Covid. Antivirals are much more promising for severe cases, but even they can’t heal ground glass in the lungs.
- tonfa 7y ago
  > If you want to detour into tinfoil hat territory, you could posit that these studies on severe patients were designed knowing it would show low or no efficacy, because it’s too late to protect the patient’s hemoglobin. I would think it is still useful because from what I've read, this protocol is often used for severe cases at the moment, so it's useful to know if it has no impact.
  - rpiguy 7y ago
    Very true. It does make sense to look at those in the most dire need first. That did not occur to me.
- nodamage 7y ago
  Isn't that paper highly theoretical at this point since it's based on computer simulations? Are there any studies on actual humans confirming the virus's effect on hemoglobin?
tgafpc2 7y ago
Maybe don't let them get that severe? One can still starve after eating.
- orwin 7y ago
  Thank you, i'm sure they are incompetent idiots that could not prevent their patients to die, after all they have graduated from a third world country and are probably not capable doctors. /s
  - ReptileMan 7y ago
    Some of the best medical minds with best education rejected evidence that washing hands before surgery saves lives for like 50 years. Anyway X doesn't work on severe cases when there is compelling anecdotal evidence that X helps on medium cases to not progress to severe is, so give them X earlier is what I read in the OP word.
deleted 7y ago
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raphlinus 7y ago
A really excellent review, published today, of the current state of knowledge on HCQ: https://blogs.sciencemag.org/pipeline/archives/2020/04/06/hydroxychloroquine-update-for-april-6 https://blogs.sciencemag.org/pipeline/archives/2020/04/06/hy... Note this is by Derek Lowe of "Things I won't work with" fame, an extremely informative series about entertainingly dangerous chemicals. And here's a new piece of candy for people who want to get their hopes up about a promising treatment: https://stm.sciencemag.org/content/early/2020/04/03/scitranslmed.abb5883 https://stm.sciencemag.org/content/early/2020/04/03/scitrans... (h/t Helen Branswell of STAT news, who is very much worth following, who retweeted Timothy Sheahan)
- dang 7y ago
  That review article was posted at https://news.ycombinator.com/item?id=22794850 https://news.ycombinator.com/item?id=22794850. We'll put it in the second-chance pool (https://news.ycombinator.com/item?id=11662380 https://news.ycombinator.com/item?id=11662380), so it will get a random placement on HN's front page. Thanks!
- deleted 7y ago
  [deleted]
- robocat 7y ago
  > a promising treatment https://stm.sciencemag.org/content/early/2020/04/03/scitranslmed.abb5883 https://stm.sciencemag.org/content/early/2020/04/03/scitrans... That is frightening. Increasing the mutation rate must carry a large unknown risk. Also surely the first thing to mutate will be self-defeating resistance to that drug...
  - raphlinus 7y ago
    The thought occurred to me as well, I got a strong sense of "playing with fire." However, viruses have a very high mutation rate as it is [1], so I'm not sure how much difference it makes. Btw, one of the best markers for overconfident but uninformed analysis is overinterpreting the fact that we have all these strains of SARS-CoV-2 as suggesting they have different degrees of infectiousness or health impacts. Certainly the different flu strains do, and, thanks to fine-grained sequencing efforts (Nextstrain in particular is doing awesome work) we can see lots of strains of this one, but Trevor Bedford has estimated that we have about a year or more before the variation in strains has an impact other than being able to "fingerprint" the chains of transmission. [1]: https://jvi.asm.org/content/92/14/e01031-17 https://jvi.asm.org/content/92/14/e01031-17
SrslyJosh 7y ago
Not very surprising given the quality of the studies that this fad is based on: https://respectfulinsolence.com/2020/04/03/zelenko-smith-abandoning-evidence-based-medicine-for-covid-19/ https://respectfulinsolence.com/2020/04/03/zelenko-smith-aba... That's a long read, but it's pretty damning. TL;DR: China says "hey, this stuff might work". French doctor conducts two very sketchy rapid-fire studies, then starts promoting himself on TV, including on Dr. Oz. No red flags there, right?
- gridlockd 7y ago
  Pretty much every virologists I listened to said "this stuff might work", because it's entirely plausible that it might work. > That's a long read, but it's pretty damning. It actually isn't. All it says is that the evidence is poor and done by people with questionable reputation. It doesn't say "it doesn't work". What if it does work, but only in the early stages, when symptoms aren't severe (yet)? You wouldn't know. Chloroquine and hydroxychloroquine are somewhat dangerous drugs and are therefore far more likely to only be given as a "last resort" rather than as a "precautionary measure", given their unproven status. What are the odds that a reputable person is going to put their reputation on the line, doing such a dangerous trial on patients that aren't at high risk? Early on, a disreputable person is way more likely to do it. There won't be any good evidence for a while, in the meantime it's all a gamble. This study is important, but limited in its scope. It shouldn't poison the well.
podgaj 7y ago
If the patients have a zinc deficient they can make all the zinc channels they want, it won't matter. It is one thing to inhibit the virus, but zinc is needed to reduce the over active immune response,
Cantbekhan 7y ago
Nobody seems to be talking about the actual reason Chinese doctors found chloroquine (and HCQ) interesting and it has nothing to do with it's immunosuppressing effect: 1) Chloroquine (and HCQ) is a zinc ionophore: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/ 2) Zinc seems to inhibit RNA polymerase of Coronaviruses in vitro https://www.researchgate.net/publication/47794995_Zn_Inhibits_Coronavirus_and_Arterivirus_RNA_Polymerase_Activity_In_Vitro_and_Zinc_Ionophores_Block_the_Replication_of_These_Viruses_in_Cell_Culture https://www.researchgate.net/publication/47794995_Zn_Inhibit... Their conclusion was that chloroquine could indeed allow zinc to enter the cell and then inhibit replication (and therefore that the treatment needed to be administered early). Nobody seems to be talking about a very easy way to verify chloroquine (and HCQ) efficiency by just using the same method used in China: Cross-check the list of patients infected with Lupus (lupus erythematosus) and with chronic HCQ treatment (they take it for years) with the list of known infected COVID19 patients. In China (and specifically in Wuhan), this is how they (team of Dr Zhang Zhan) found out about the efficiency of HCQ. They noticed that there were no patients with chronic HCQ treatment for lupus (lupus erythematosus) infected with covid19. This was in peoples Hospital of Wuhan University (source: https://www.jqknews.com/news/388543-The_novel_coronavirus_pneumonia_has_short_term_curative_effect_on_the_treatment_of_new_crown_pneumonia.html https://www.jqknews.com/news/388543-The_novel_coronavirus_pn...) This alone would be enough to prove some efficiency even as prophyalxis (as they are advocating officially in India). This should be quite trivial to check with the current amount of confirmed infection. These details were all explained in this medcram vid: https://www.youtube.com/watch?v=Eeh054-Hx1U https://www.youtube.com/watch?v=Eeh054-Hx1U
- nradov 7y ago
  In principle that would be a great thing to check but due to lack of clinical systems interoperability it's not at all trivial to check. Surescripts and the various pharmacy chains have data on who has been taking chloroquine but researchers will still have to get access, and then do a bunch of record linkage work to compare outcomes. In the hardest hit areas I suspect healthcare providers have also fallen behind on data entry so there's going to be a data quality problem.
anigbrowl 7y ago
The lack of productive discussion around a potential treatment tells us more about our bad decision-making under anxiety conditions than it does about the efficacy or not of the medical proposal. Although I posted a preprint of the French micro-study to HN a few weeks ago when this first became a topic of discussion, I now regret doing so due to the subsequent public confusion and imho very irresponsible promotion of it as a harm-free prophylactic by Trump.
OniBait 7y ago
Nobody is going to point out that of the 11 patients, "8 had significant comorbidities associated with poor outcomes (obesity: 2; solid cancer: 3; hematological cancer: 2; HIV-infection: 1)"? I don't even understand what the point of this study was except as a rebuttal to the prior study. I mean, if people thought the prior study was cherry picking results. I don't even know what I'd call this... There's _some_ anecdotal evidence that it _may_ work if treated early. Hopefully there are some real studies that are being done on that.
libpcap 7y ago
Prescribe it before it gets severe then.
perl4ever 7y ago
I have no medical expertise, but there's something that is confusing me. From what I read, typically, you get the virus, then an opportunistic bacterium gives you pneumonia, and that's what you die from. But this study seems to be saying "someone else found these meds reduced the virus and we didn't". But the meds are more or less antibiotics, aren't they? So could the explanation simply be that while the virus is the same, the bacteria are not, in the two tests?
- Gibbon1 7y ago
  My understanding is what you said is true for influenza and to a lesser extent colds. Those virus tend infect the upper respiratory system. COVID19 though can infect the lower lungs and directly causes pneumonia. And viral pneumonia is no joke even before COVID19.
- jfnixon 7y ago
  Some antibacterials have antiviral properties. https://erj.ersjournals.com/content/36/3/646 https://erj.ersjournals.com/content/36/3/646
ruggi 7y ago
An in-vitro pre-print study ( https://www.biorxiv.org/content/10.1101/2020.03.29.014407v1 https://www.biorxiv.org/content/10.1101/2020.03.29.014407v1 ) showed that administering Hydroxychloroquine only after Covid-19 infection is not helping much, while administering it both before the infection and after the infection gives great outcomes. They tried different administration modalities of HCQ to in-vitro infected cells: some cells got nothing (control), some got HCQ only before infection, some got HCQ only after infection, some got HCQ both before and after infection. THe cells that got HCQ only before or only after infection had just slightly better outcome than control (they appear as heavily infected), while cells that received HCQ both before and after contagion were in much healthier conditions. If that would be the same in vivo as in vitro, that would entail that it would be possible to use HCQ as prophylaxis, given that the patients never stop taking the drug. Of course the caveat is "IF that would be the same in vivo as in vitro", that they didn't (yet) tested.

123 points by aazaa 7y ago

I am not in any way qualified in the medical domain but these methods look similar to the other Study that was viewed as flawed that showed it did work. Seems there is no solid data either way.

archgoon 7y ago
Which, in itself, is probably a valuable take-away.
arrrg 7y ago
These studies tell me mostly that if there is an effect it’s probably not a large one.
malpighien 7y ago
Well this one seems more rigorous. They monitored concentration in blood for 4 days, they checked viral presence two following days at the end. They don't mention viral load though and I don't know if they have a threshold for cycles in QPCR to estimate that. This kind of paper is not here to say here is the proof it works or it does not work, it is meant to say: this what we had with us, this how we did it, this is the results we observed and whether or not it validates the hypothesis stated.

sdiq 7y ago

https://abc7news.com/amp/coronavirus-drug-covid-19-malaria-hydroxychloroquine/6079864/ https://abc7news.com/amp/coronavirus-drug-covid-19-malaria-h... Not a study but just another anecdote. Using zinc this time round rather than azithromycin.

snapetom 7y ago
Yeah, I don't know what's the point of these studies that don't look at HCQ+zinc when the hypothesis is that HCQ promotes zinc absorption.
- HarryHirsch 7y ago
  The hypothesis is that hydroxychloroquin interferes with glycosylation of cell surface proteins that are essential for entry of the virus into the cell. The zinc notion is total bunk, intracellular zinc concentration is tightly controlled. Random zinc excursions just don't happen, if they did they would result in death.
  - podgaj 7y ago
    This is so wrong I do not know where to start. ADAM17 is responsible for shedding of ACE2 from the cell which creates soluble ACE2. If ACE2 is not ON the cell the virus cannot infect the cell. ADAM17, like ACE2 is a zinc finger protein and uses zinc as a cofactor. Also, zinc is widely understood to lower the immune response by affecting interferon levels. It is not only about intracellular zinc. But in a deficiency intracellular zinc has even less chance of being brought into the cell, right? To say that zinc does not matter because hydroxychloroquin is absurd.
  - giardini 7y ago
    HarryHirsch says "The zinc notion is total bunk..." I am unclear what you mean here but this in-vitro experiment. which studied interaction of zinc ions with chloroquine in a human ovarian cancer cell line. shows far more zinc entering cells that are exposed to chloroquine: "Chloroquine Is a Zinc Ionophore": https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/
- pengaru 7y ago
  Isn't there always going to be some ambient zinc available even without additional supplementing? I imagine there'd be some evidence of efficacy regardless, but this is nowhere near my area of expertise.
klipt 7y ago
I hate the way this drug has been politicized by Trump yapping it up before there were any good studies. Politicians should shut up about unproven medicines and leave it to the professionals to actually practice, you know, evidence based medicine.
- betterunix2 7y ago
  "Politicians should shut up and leave it to the professionals" FTFY.
  - giardini 7y ago
    A political leader's role is not to choose medications but to give people hope and to keep the wheels of society rolling. But no matter what, there will always be more questions about what will be done. I think Trump was sufficiently vague yet optimistic in his answers, as befits his role. Consider how different it would have been had he said "We know of nothing that works against this virus." or even worse, "We're screwed! Go home and tell your children we're all gonna die!".

sna1l 7y ago

n = 11?

michael_storm 7y ago
Believe it or not, it's pretty hard to conduct a large-scale study in the middle of the largest pandemic in modern history.
- rattray 7y ago
  Why is that?
- monadic2 7y ago
  I'd estimate they were commenting on the quality of the results, not critiquing the personal efforts of the researchers.
- SpicyLemonZest 7y ago
  I don’t believe it. Studying how to effectively treat coronavirus patients is literally the most important problem in the world right now, and I’m sure a lot more than 11 severe cases are being treated with hydrochloroquine.
  - kilbuz 7y ago
    While your point is a good one, meaningful clinical research is hard enough under normal conditions. Forms, enrollment, protocols, data collection, statistical analysis plans, reporting, etc. It's an entire industry used to operating in scales that often span years for a single meaningful study.
    - SpicyLemonZest 7y ago
      And I agree with that as far as it goes, but I think it reflects the problem - clinical research contains a bunch of hurdles that have nothing to do with uncovering the truth. So in a sudden emergency, where clinical research starts to diverge from the treatment decisions of doctors and the drug supply actions of governments, I'm not going to put much weight on clinical research.

trhway 7y ago

[IANAD] hydroxychloroquine is an immunosuppressant and shouldn't be combined even with vaccines ( https://www.medicinenet.com/hydroxychloroquine/article.htm#which_drugs_or_supplements_interact_with_hydroxychloroquine_plaquenil https://www.medicinenet.com/hydroxychloroquine/article.htm#w... ), so using it when immune system is really fighting an infection may happen to be very antiproductive unless it is a case of COVID triggered cytokine storm (hyperinflammation) when such immunosuppressant is probably what you'd really want. May be it is a reason why in come cases of COVID it works and in some doesn't. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6... "However, in hyperinflammation, immunosuppression is likely to be beneficial. Re-analysis of data from a phase 3 randomised controlled trial of IL-1 blockade (anakinra) in sepsis, showed significant survival benefit in patients with hyperinflammation, without increased adverse events.8 A multicentre, randomised controlled trial of tocilizumab (IL-6 receptor blockade, licensed for cytokine release syndrome), has been approved in patients with COVID-19 pneumonia and elevated IL-6 in China " Notable fact is that majority of the deaths of the second wave (the deadliest, which in addition to children/weak/elderly was also strongly hitting healthy 25-35 years old) of Spanish flu was due to cytokine storm.

orwin 7y ago
Yes, obviously in case of hyperinflammation doctor are giving immunosuppressing drugs, HCQ or other depending on the stocks (and of course the patient history and other drugs given prior). They are very capable people in most cases, urgentists are often very knowledgable, and reanimation doctors are probably the best at interfering/preventing coktail effect. They are not available in all cases, but they try to be there for the most important ones. No one, no scientist is saying with certainty that HCQ does not work at all. However, the maxim is primum non nocere. Are HCQ effects important enough to use it in every case when you can do otherwise? Well, according to the last Raoult study on 80 mild cases, no. 3 hospitalisation, 1 death for 80 cases is around the same result as German/S.K. mild cases who are given no treatment at all (a bit superior, even, but n=80 is clearly not enough). Maybe HCQ reduce contagiosity. In this case, is HCQ more efficient than interferon? I know that i would prefer interferon as my liver and kidneys can take more hit than my heart atm (i already have a medication that cause tachycardia when i overdose it a little + some minor heart issues). Is HCQ more efficient than rinovir? this particular article seems to say that it's not but why should i trust this article more than Raoult and some French articles? Should i take everything (interferon, rinovir, HCQ, CQ) and hope for the best? Or, since i can afford to as i live in a rich country, should i wait the different study results?

sunsu 7y ago

By the time it's severe, it's often too late: https://twitter.com/yishan/status/1244717172871409666?s=20 https://twitter.com/yishan/status/1244717172871409666?s=20

webmobdev 7y ago

Wonder when the Indian Council of Medical Research will release more papers - there were a few patients who responded positively under their suggested treatment plan: > “We used a combo of Lopinavir and Ritonavir drugs which are usually given as a second line of treatment for HIV with drugs meant for curing malaria and swine flu. We administered this line of treatment to a 70-year-old Italian woman, who had come as a tourist to Rajasthan, who tested positive and was being treated by us, as well as another Italian, who is 69-year-old,” said Dr Sudhir Bhandari. > ... “The team of doctors under the leadership of Dr Sudhir Bhandari, Principal of SMS Medical College held consultations with the ICMR and tried a combination medicines given for malaria, swine flu (Tamiflu) along with drugs for HIV and it worked well. All three persons including the Italians were cured this way,” said Rohit Kumar Singh, additional chief secretary, health of Rajasthan government. Source: https://www.nationalheraldindia.com/india/three-coronavirus-afflicted-patients-recover-due-to-innovative-treatment-by-doctors-at-jaipur-govt-hospital https://www.nationalheraldindia.com/india/three-coronavirus-... > ... The three persons who tested positive were administered a combination of 200mg Lopinavir and 50 mg of Ritonavir twice a day besides Oseltamivir and Chloroquine that are given to the swine flu and malaria patients. > However, the doctors at the SMS Hospital warned that this was only an emergency treatment and the HIV medicines were used only as an emergency measure that could help in regaining normalcy. Source: https://www.nationalheraldindia.com/india/covid-19-magic-medicine-of-jaipurs-hospital-cures-3-patients-draws-attention-in-medical-world https://www.nationalheraldindia.com/india/covid-19-magic-med...

webmobdev 7y ago
Update: The Indian Council of Medical Research has also given the go ahead to try out plasma therapy for the really serious, and some hospitals and institute are waiting for clearance of the same from the Drug Controller General of India: > ... Blood for the plasma therapy will be collected from recovered patients at SCTIMST and the medical colleges and donated to critical patients with sanction from Blood Transfusion Council. Plasma would be separated from blood and taken to other hospitals under refrigeration. > ... When a person suffers from COVID-19, antibodies are created in his or her body as defence. Such B lymphocytes would be present in plasma. After a patient recovers from the disease, these antibodies remain in blood to prevent another attack by the virus. The plasma collected from such people and given to another patient would have antibodies which target the virus and prevent the recipient from slipping into a more serious condition. According to researches, plasma taken from one donor would have sufficient doses for two patients. Source: https://english.manoramaonline.com/news/kerala/2020/04/09/kerala-plans-trials-in-convalescent-plasma-therapy-against-covid.html https://english.manoramaonline.com/news/kerala/2020/04/09/ke...

rodgerd 7y ago

So a bunch of people who have medical conditions which actually respond to HCQ have lost access to it, for no benefit to anyone else. Great.

transreal 7y ago
Unfortunately, I'm one of those people. My last refill ran out last week, and my pharmacist doesn't think I can get a refill anytime soon :-( Fortunately my condition is not life threatening or severe, but it's something I've been living with for many years, and the HCQ was just finally getting it under control, so it's a bummer that there is so much hoarding going on before we even know if it really works for Covid-19. Also, it is not a risk free medication. While it's generally safe, my doctor makes me get frequent lab work & a vision test because the side effects can be pretty bad for a small minority of people.

rpiguy 7y ago

COVID-19 attacks hemoglobin and that is how it damages the lungs. With your hemoglobin unable to exchange oxygen with blood in the lungs, it causes terrible damage. 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... Chloroquine prevents the virus from affecting hemoglobin, or reduces the effect. This is also how Chloroquine treats malaria. The problem with a study on severe cases is that the damage is already done and the hemoglobin is already compromised. It is best to start treatment with chloroquine prior to reaching the severe stage. By the time you are severe you’ve gotten permanent lung damage and the immune system is in a race condition unable to keep up with the virus. If you want to detour into tinfoil hat territory, you could posit that these studies on severe patients were designed knowing it would show low or no efficacy, because it’s too late to protect the patient’s hemoglobin. Azithromycin slows ribosonal RNA replication in bacteria. It is unclear how it helps with a Covid. Antivirals are much more promising for severe cases, but even they can’t heal ground glass in the lungs.

tonfa 7y ago
> If you want to detour into tinfoil hat territory, you could posit that these studies on severe patients were designed knowing it would show low or no efficacy, because it’s too late to protect the patient’s hemoglobin. I would think it is still useful because from what I've read, this protocol is often used for severe cases at the moment, so it's useful to know if it has no impact.
- rpiguy 7y ago
  Very true. It does make sense to look at those in the most dire need first. That did not occur to me.
nodamage 7y ago
Isn't that paper highly theoretical at this point since it's based on computer simulations? Are there any studies on actual humans confirming the virus's effect on hemoglobin?

tgafpc2 7y ago

Maybe don't let them get that severe? One can still starve after eating.

orwin 7y ago
Thank you, i'm sure they are incompetent idiots that could not prevent their patients to die, after all they have graduated from a third world country and are probably not capable doctors. /s
- ReptileMan 7y ago
  Some of the best medical minds with best education rejected evidence that washing hands before surgery saves lives for like 50 years. Anyway X doesn't work on severe cases when there is compelling anecdotal evidence that X helps on medium cases to not progress to severe is, so give them X earlier is what I read in the OP word.

deleted 7y ago

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raphlinus 7y ago

A really excellent review, published today, of the current state of knowledge on HCQ: https://blogs.sciencemag.org/pipeline/archives/2020/04/06/hydroxychloroquine-update-for-april-6 https://blogs.sciencemag.org/pipeline/archives/2020/04/06/hy... Note this is by Derek Lowe of "Things I won't work with" fame, an extremely informative series about entertainingly dangerous chemicals. And here's a new piece of candy for people who want to get their hopes up about a promising treatment: https://stm.sciencemag.org/content/early/2020/04/03/scitranslmed.abb5883 https://stm.sciencemag.org/content/early/2020/04/03/scitrans... (h/t Helen Branswell of STAT news, who is very much worth following, who retweeted Timothy Sheahan)

dang 7y ago
That review article was posted at https://news.ycombinator.com/item?id=22794850 https://news.ycombinator.com/item?id=22794850. We'll put it in the second-chance pool (https://news.ycombinator.com/item?id=11662380 https://news.ycombinator.com/item?id=11662380), so it will get a random placement on HN's front page. Thanks!
deleted 7y ago
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robocat 7y ago
> a promising treatment https://stm.sciencemag.org/content/early/2020/04/03/scitranslmed.abb5883 https://stm.sciencemag.org/content/early/2020/04/03/scitrans... That is frightening. Increasing the mutation rate must carry a large unknown risk. Also surely the first thing to mutate will be self-defeating resistance to that drug...
- raphlinus 7y ago
  The thought occurred to me as well, I got a strong sense of "playing with fire." However, viruses have a very high mutation rate as it is [1], so I'm not sure how much difference it makes. Btw, one of the best markers for overconfident but uninformed analysis is overinterpreting the fact that we have all these strains of SARS-CoV-2 as suggesting they have different degrees of infectiousness or health impacts. Certainly the different flu strains do, and, thanks to fine-grained sequencing efforts (Nextstrain in particular is doing awesome work) we can see lots of strains of this one, but Trevor Bedford has estimated that we have about a year or more before the variation in strains has an impact other than being able to "fingerprint" the chains of transmission. [1]: https://jvi.asm.org/content/92/14/e01031-17 https://jvi.asm.org/content/92/14/e01031-17

SrslyJosh 7y ago

Not very surprising given the quality of the studies that this fad is based on: https://respectfulinsolence.com/2020/04/03/zelenko-smith-abandoning-evidence-based-medicine-for-covid-19/ https://respectfulinsolence.com/2020/04/03/zelenko-smith-aba... That's a long read, but it's pretty damning. TL;DR: China says "hey, this stuff might work". French doctor conducts two very sketchy rapid-fire studies, then starts promoting himself on TV, including on Dr. Oz. No red flags there, right?

gridlockd 7y ago
Pretty much every virologists I listened to said "this stuff might work", because it's entirely plausible that it might work. > That's a long read, but it's pretty damning. It actually isn't. All it says is that the evidence is poor and done by people with questionable reputation. It doesn't say "it doesn't work". What if it does work, but only in the early stages, when symptoms aren't severe (yet)? You wouldn't know. Chloroquine and hydroxychloroquine are somewhat dangerous drugs and are therefore far more likely to only be given as a "last resort" rather than as a "precautionary measure", given their unproven status. What are the odds that a reputable person is going to put their reputation on the line, doing such a dangerous trial on patients that aren't at high risk? Early on, a disreputable person is way more likely to do it. There won't be any good evidence for a while, in the meantime it's all a gamble. This study is important, but limited in its scope. It shouldn't poison the well.

podgaj 7y ago

If the patients have a zinc deficient they can make all the zinc channels they want, it won't matter. It is one thing to inhibit the virus, but zinc is needed to reduce the over active immune response,

Cantbekhan 7y ago

Nobody seems to be talking about the actual reason Chinese doctors found chloroquine (and HCQ) interesting and it has nothing to do with it's immunosuppressing effect: 1) Chloroquine (and HCQ) is a zinc ionophore: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/ 2) Zinc seems to inhibit RNA polymerase of Coronaviruses in vitro https://www.researchgate.net/publication/47794995_Zn_Inhibits_Coronavirus_and_Arterivirus_RNA_Polymerase_Activity_In_Vitro_and_Zinc_Ionophores_Block_the_Replication_of_These_Viruses_in_Cell_Culture https://www.researchgate.net/publication/47794995_Zn_Inhibit... Their conclusion was that chloroquine could indeed allow zinc to enter the cell and then inhibit replication (and therefore that the treatment needed to be administered early). Nobody seems to be talking about a very easy way to verify chloroquine (and HCQ) efficiency by just using the same method used in China: Cross-check the list of patients infected with Lupus (lupus erythematosus) and with chronic HCQ treatment (they take it for years) with the list of known infected COVID19 patients. In China (and specifically in Wuhan), this is how they (team of Dr Zhang Zhan) found out about the efficiency of HCQ. They noticed that there were no patients with chronic HCQ treatment for lupus (lupus erythematosus) infected with covid19. This was in peoples Hospital of Wuhan University (source: https://www.jqknews.com/news/388543-The_novel_coronavirus_pneumonia_has_short_term_curative_effect_on_the_treatment_of_new_crown_pneumonia.html https://www.jqknews.com/news/388543-The_novel_coronavirus_pn...) This alone would be enough to prove some efficiency even as prophyalxis (as they are advocating officially in India). This should be quite trivial to check with the current amount of confirmed infection. These details were all explained in this medcram vid: https://www.youtube.com/watch?v=Eeh054-Hx1U https://www.youtube.com/watch?v=Eeh054-Hx1U

nradov 7y ago
In principle that would be a great thing to check but due to lack of clinical systems interoperability it's not at all trivial to check. Surescripts and the various pharmacy chains have data on who has been taking chloroquine but researchers will still have to get access, and then do a bunch of record linkage work to compare outcomes. In the hardest hit areas I suspect healthcare providers have also fallen behind on data entry so there's going to be a data quality problem.

anigbrowl 7y ago

The lack of productive discussion around a potential treatment tells us more about our bad decision-making under anxiety conditions than it does about the efficacy or not of the medical proposal. Although I posted a preprint of the French micro-study to HN a few weeks ago when this first became a topic of discussion, I now regret doing so due to the subsequent public confusion and imho very irresponsible promotion of it as a harm-free prophylactic by Trump.

OniBait 7y ago

Nobody is going to point out that of the 11 patients, "8 had significant comorbidities associated with poor outcomes (obesity: 2; solid cancer: 3; hematological cancer: 2; HIV-infection: 1)"? I don't even understand what the point of this study was except as a rebuttal to the prior study. I mean, if people thought the prior study was cherry picking results. I don't even know what I'd call this... There's _some_ anecdotal evidence that it _may_ work if treated early. Hopefully there are some real studies that are being done on that.

libpcap 7y ago

Prescribe it before it gets severe then.

perl4ever 7y ago

I have no medical expertise, but there's something that is confusing me. From what I read, typically, you get the virus, then an opportunistic bacterium gives you pneumonia, and that's what you die from. But this study seems to be saying "someone else found these meds reduced the virus and we didn't". But the meds are more or less antibiotics, aren't they? So could the explanation simply be that while the virus is the same, the bacteria are not, in the two tests?

Gibbon1 7y ago
My understanding is what you said is true for influenza and to a lesser extent colds. Those virus tend infect the upper respiratory system. COVID19 though can infect the lower lungs and directly causes pneumonia. And viral pneumonia is no joke even before COVID19.
jfnixon 7y ago
Some antibacterials have antiviral properties. https://erj.ersjournals.com/content/36/3/646 https://erj.ersjournals.com/content/36/3/646

ruggi 7y ago

An in-vitro pre-print study ( https://www.biorxiv.org/content/10.1101/2020.03.29.014407v1 https://www.biorxiv.org/content/10.1101/2020.03.29.014407v1 ) showed that administering Hydroxychloroquine only after Covid-19 infection is not helping much, while administering it both before the infection and after the infection gives great outcomes. They tried different administration modalities of HCQ to in-vitro infected cells: some cells got nothing (control), some got HCQ only before infection, some got HCQ only after infection, some got HCQ both before and after infection. THe cells that got HCQ only before or only after infection had just slightly better outcome than control (they appear as heavily infected), while cells that received HCQ both before and after contagion were in much healthier conditions. If that would be the same in vivo as in vitro, that would entail that it would be possible to use HCQ as prophylaxis, given that the patients never stop taking the drug. Of course the caveat is "IF that would be the same in vivo as in vitro", that they didn't (yet) tested.