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Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro

Jia Liu, Ruiyuan Cao, Mingyue Xu

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Xi Wang, Huanyu Zhang, Hengrui Hu, Yufeng Li, Zhihong Hu, Wu Zhong, Manli Wang

2020 · Cell Discovery

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Original HN comments, with labels from simple text rules. A label describes the whole comment and may miss context or irony. Read the discussion to make up your own mind. About the labels

10 selected excerpts · 10 total mentions

squibbles
Neutral mention · rule
I don't think the mass media is a reliable or accurate source for learning about or promulgating scientific findings. Most medical research is fraught with ambiguity and mixed messages, simply because of the phenotypic variance found in humans (and other organisms). (See more about phenotypic variance here: [0]) Generally speaking, different organisms will respond differently to the same environmental stimuli. This is why drug trials require large sample sizes and extended periods of time to assess efficacy and safety. With regard to hydroxychloroquine (HCQ), there is nothing that could be considered definitive about its efficacy or safety for all people when used as an…
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off-label treatment for COVID-19. While there is evidence that (in some people) is does not reduce the viral load ("Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues." [1]), there is evidence that HCQ "... can significantly decrease the production of cytokines and, in particular, pro-inflammatory factors" [2] and HCQ has "... potential, but controversial, characteristics to combat pathological inflammation associated with COVID-19." [3] Of course, raw research does not give a definitive answer about efficacy and safety for all people, but it does suggest that HCQ may be one possible treatment (perhaps preventative, perhaps in vitro) for inflammation, which is one of the serious complications of COVID-19. It will likely be years before the mechanisms of COVID-19 are well understood. In fact, it is likely that some other urgent calamity will come along and compete for research funds currently used for COVID-19 research, which could significantly extend the time it takes to understand the SARS-CoV-2 virus. [0] https://www.nature.com/scitable/topicpage/adaptation-and-phe... [1] https://www.nature.com/articles/s41586-020-2558-4 [2] https://www.nature.com/articles/s41421-020-0156-0 [3] https://www.nature.com/articles/s41419-020-2721-8
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jamesblonde
Neutral mention · rule
My immediate reaction was that I would not expect to see an effect if you are giving HCQ to patients after they have been hospitalized by the virus. You are now into the inflamation/cytokine storm phase of COVID-19. The best chance of HCQ working is very early, ideally before or directly after exposure. The jury is still out if you take HCQ after the onset of sympthoms if that is also too late. Based on this in-vitro study - https://www.nature.com/articles/s41421-020-0156-0 - if I hypothetically had both Chloroquine (CQ) and Hydroxychloroquine (HCQ), I would prefer HCQ for prophylaxis/pre-sympthoms, but if I was sympthomatic, I would choose CQ. The loading time or HCQ is longer and it appears less effective at higher MOIs "the data suggest that the anti-SARS-CoV-2 activity of HCQ seems to be less potent compared to CQ, at least at certain MOIs."
Original comment Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients
apendleton
Neutral mention · rule
There's some evidence now that viral load peaks in the first week, and it's the second week that tends to be a problem for people with very serious cases. By the time many of these patients are hospitalized, their viral load is already going down on its own, and their serious complications are either due to immune overreaction (the so-called "cytokine storm"), or some sort of opportunistic co-infection like bacterial pneumonia. It's decently likely from what I've been reading that there might end up being effective pharmaceuticals for each stage, but that they'll be totally different from one another: maybe HCQ and antivirals like remdesivir or favipiravir early, and…
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maybe immune-modulators like tocilizumab or even corticosteroids in this second phase. But again, the devil will be in the details, as it looks like HCQ doesn't work late, and steroids or other immune modulators might be actively harmful in that first stage when the virus is still surging. As for mechanism: nobody is really sure. HCQ does have some immune-modulating effects (that's what makes it useful for lupus), but there's also speculation that it might have some effect on the interaction between the ACE2 receptor and the coronavirus spike protein, and so somehow inhibit viral entry (see, e.g., https://www.nature.com/articles/s41421-020-0156-0).
Original comment Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients
ph0rque
Neutral mention · rule
It irks me to see chloroquine and hydroxychloroquine being used interchangeably in the media. This study used chloroquine. Trump touted hydroxychloroquine. "Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro" https://www.nature.com/articles/s41421-020-0156-0
Original comment Chloroquine trial halted after 11 patients die on high dose
jojo2000
Neutral mention · rule
Hello, and thank you ! Exploring the dependency graph of this paper is a good starter [0] [0] https://www.nature.com/articles/s41421-020-0156-0 Yes, you start with molecular studies, then in-vitro, then in-vivo, then in humans, and in the end, sometimes it gives good results, sometimes not.
Original comment More on chloroquine/azithromycin and on Dr. Raoult
Reelin
Neutral mention · rule
CQ (and HCQ, etc) have multiple potential mechanisms of action. I don't believe we know how it works in this particular case yet, or if it even works at all. It is indeed a zinc ionophore, [1] and those are known to impair the replication of a number of RNA viruses. [2] However, there are a number of other mechanisms at play here as well. [3] > Both CQ and HCQ are weak bases that are known to elevate the pH of acidic intracellular organelles, such as endosomes/lysosomes, essential for membrane fusion5. In addition, CQ could inhibit SARS-CoV entry through changing the glycosylation of ACE2 receptor and spike protein6. Time-of-addition experiment confirmed that HCQ…
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effectively inhibited the entry step, as well as the post-entry stages of SARS-CoV-2, which was also found upon CQ treatment (Supplementary Fig. S2). [1] https://journals.plos.org/plosone/article?id=10.1371/journal... [2] https://journals.plos.org/plospathogens/article?id=10.1371/j... [3] https://www.nature.com/articles/s41421-020-0156-0
Original comment First hydroxychloroquine randomized controlled trial: results disappointing
swebs
Neutral mention · rule
>Note that there doesn't appear to be any evidence yet that chloroquine is effective in COVID-19 treatment. So far it has been studied only for other types of coronavirus. Seriously? It seems like every few days a new study pops up here. https://www.nature.com/articles/s41421-020-0156-0.pdf https://www.mediterranee-infection.com/wp-content/uploads/20... https://clinicaltrials.gov/ct2/show/NCT04307693 https://www.sciencedirect.com/science/article/pii/S092485792... It seemed like there was no shortage of praise for this drug in the media, until president Trump mentioned it and then all the talking heads did a complete 180.
Original comment Man dies after self-medicating with chloroquine
ekianjo
Neutral mention · rule
Is there a reason to believe the viral load in the throat and the lungs would not follow the same trend? And you also forget to mention this (CQ and HCQ concentrate in certain organs): > It has been reported that oral absorption of CQ and HCQ in humans is very efficient. In animals, both drugs share similar tissue distribution patterns, with high concentrations in the liver, spleen, kidney, and lung reaching levels of 200–700 times higher than those in the plasma10. It was reported that safe dosage (6–6.5 mg/kg per day) of HCQ sulfate could generate serum levels of 1.4–1.5 μM in humans11. Therefore, with a safe dosage, HCQ concentration in the above tissues is likely to be achieved to inhibit SARS-CoV-2 infection. https://www.nature.com/articles/s41421-020-0156-0
Original comment About that Hydroxychloroquine for Covid-19 trial
jamesblonde
Neutral mention · rule
Yes, that was my immediate take on the paper. However, the jury is still out if you take HCQ after the onset of sympthoms if that is also too late. Based on this in-vitro study - https://www.nature.com/articles/s41421-020-0156-0 - if I hypothetically had both Chloroquine (CQ) and Hydroxychloroquine (HCQ), I would prefer HCQ for prophylaxis, but if I was exposed and likely infected or developed sympthoms, I would choose CQ. The loading time or HCQ is longer and it appears less effective at higher MOIs "the data suggest that the anti-SARS-CoV-2 activity of HCQ seems to be less potent compared to CQ, at least at certain MOIs."
Original comment No evidence of clinical efficacy of hydroxychloroquine in Covid-19 Patients [pdf]

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