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Covid-19’s stop-gap solution until vaccines and antivirals are ready
- DarmokJalad1701 7y agoThis may be a stupid question. But can the antibodies be synthesized based on samples from recovered patients? If not, why?
- jliptzin 7y agoDefinitely not a stupid question
- felipemnoa 7y agoFollowing your train of thought, could the synthesis be done in the same way that insulin is currently created? i.e. Have some germs synthesize the antibodies.
- chispamed 7y agoYes, that’s a possibility and currently many monoclonal antibodies are produced that way (basically all drugs ending in “-mab”). However the process is costly and current capacities are not sufficient to supply a whole population regularly with antibodies which is why we still use some older drugs for certain diseases (think MTX for rheumatoid arthritis) and reserve monoclonal antibodies for treatment-resistant cases. I hope that it’ll be possible to protect high risk HCW and ICU patients through antibodies and thereby bring down Covid’s mortality soonish but we still need to buy some time until then and work on a vaccine to protect the population long-term. Right now what we need to do is stay at home and invest in medical care and drug development but with emphasis on the staying at home part because it’s the necessary condition for everything else to work.
- felipemnoa 7y agoThanks for your reply. Very informative.
- ethbro 7y agoNot stupid. NOTE: Not my field, so speaking off basic knowledge here. Happy to be corrected. Tl;dr: because biology at scale is complicated. Longer-form, because antibodies and immunological response are somewhat complicated. Knowing what an antibody looks like, how to produce it, and how to scale that production in a safe and reliable way are all very different things. Older article, but general concepts: http://neobiolab.com/research/in-vitro-and-in-vivo-production-of-antibodies http://neobiolab.com/research/in-vitro-and-in-vivo-productio... ... And because the in vivo methods we know of are ethically dicey. To rephrase it in rough terms -- creating custom cancers that produce the thing we want and giving them to mice, then harvesting concentrated antibodies from the tumors. See: https://en.wikipedia.org/wiki/Hybridoma_technology https://en.wikipedia.org/wiki/Hybridoma_technology
- snowmaker 7y agoYes, and there are companies working on exactly this. Abcellera is furthest along: https://www.fiercebiotech.com/biotech/lilly-taps-abcellera-to-get-coronavirus-drug-into-clinic-4-months https://www.fiercebiotech.com/biotech/lilly-taps-abcellera-t...
- boticus_prime 7y agohttps://www.fiercebiotech.com/research/fast-moving-regeneron-eyes-summer-clinical-trial-for-covid-19-antibody-cocktail-therapy https://www.fiercebiotech.com/research/fast-moving-regeneron... >Regeneron scientists have isolated hundreds of neutralizing antibodies against the SARS-CoV-2 virus from a humanized mouse model as well as from humans who have recovered from COVID-19, the company said Tuesday.
- whoisjuan 7y agoYes. Synthetic antibodies are a thing, but they are very expensive and very hard to produce (from what I inderstand). Using animals when possible (for example horses, for the production of snake venom antidotes) seems more efficient in cost, volume and time. Take for instance this crisis. They just need the plasma of immune individuals to give temporary immunity to sick or at risk individuals. It doesn’t scale but it works. Some good basic reads: Antigens - https://en.m.wikipedia.org/wiki/Antigen https://en.m.wikipedia.org/wiki/Antigen Humoral Inmunity -https://en.m.wikipedia.org/wiki/Humoral_immunity https://en.m.wikipedia.org/wiki/Humoral_immunity Synthetic antibodies -https://en.m.wikipedia.org/wiki/Synthetic_antibody https://en.m.wikipedia.org/wiki/Synthetic_antibody Antibodies memetic - https://en.m.wikipedia.org/wiki/Antibody_mimetic https://en.m.wikipedia.org/wiki/Antibody_mimetic
- andreareina 7y agoProtein synthesis is complicated. Antivenom is still produced in the same way: inject an animal with small doses of venom, collect the antibodies from the plasma. [1] https://en.wikipedia.org/wiki/Antivenom https://en.wikipedia.org/wiki/Antivenom
- ars 7y agoThat's basically what a https://en.wikipedia.org/wiki/Monoclonal_antibody https://en.wikipedia.org/wiki/Monoclonal_antibody is - and those are by far the most expensive drugs there are, with costs in the $100,000/person range.
- freepor 7y agoWhat would the costs look like if the market scaled up by 1000 or 10000x?
- acqq 7y agoThe cost comes from the nonscalability of both the production and the use.
- jlokier 7y agoWhat are the main obstacles to scalability of production and of use? Could the former be amenable to treatment as an engineering problem? There are a lot of motivated engineering minds right now.
- acqq 7y agoI'm not a professional in that area, just based on what I've read, so in case of doubt, check better sources: If you use human donors, you need trained doctors spending time and equipment to select the donors, handle the donors, take care of them during the donation which takes hours (the needle is stuck in their vein during that time), trained professionals using expensive equipment to process the donation, and then trained doctors to perform the infusion on the patient, an hour or two, but you still want keep the patient in the hospital overnight in case of complications, which do happen often enough that it was practice to do so: as in, once in thousand. At the end all that work, it is relatively sure that the described work could result in protection of exactly one patient more than before you started. The percentage of known complications and the potential for failure in every step is what makes it non scalable. With non human donors you can avoid some work, but the second part remains: it's not "just a shot" like when you do a vaccination which is scalable. And while vaccination is scalable, if you're going to vaccinate billions, you also want to be very sure you aren't harming them, that's why speeding up vaccine production is not scalable. Even producing the vaccines is not easy at all to scale. It's not that nobody has attempted hard to achieve this up to now.
- echelon 7y agoYou need to create a cell line. Many medicines today use murine (mouse) monoclonal antibodies.
- mtsr 7y agoA monoclonal antibody (-mab) already existed in a lab in the Netherlands, because it had been developed for SARS and turned out to work for SARS-CoV-2. But it will take weeks before this can be industrialized, let alone approved.
- dnautics 7y agoNot really in time. In principle, yes, but antibodies are more complicated than normal molecules (glycosylation, protein folding) so you can really only industrially prepare them in certain types of cells (pretty much Chinese Hamster Ovary, last I checked). Another problem is retrieving the correct antibody gene sequence. All immunoactive antibodies have been subjected to a process of internal evolution and artificial selection. Their DNA is not the same as your germline DNA, through shuffling and active mutation events, and indeed every immune cell that produces antibodies has different DNA than the other ones (that haven't been told to clone themselves) so it's really difficult to retrieve the correct gene sequence. In practice I wouldn't estimate it to be possible to do this in the 4-6 month timeframe. Maybe in the 6-12 month timeframe under emergency duress situations.
- fernly 7y agoCould somebody with medical knowledge speak to the lifetime of exogenous antibodies in another person's blood? And, does their presence in any way "train" the host immune system to make more? Or is the benefit solely from the introduced antibodies?
- ghufran_syed 7y agoThe half-life of exogenous antibodies is around one month: https://pubmed.ncbi.nlm.nih.gov/3183495/ https://pubmed.ncbi.nlm.nih.gov/3183495/ The benefit is solely from the antibodies attacking and reducing the level of virus in the body, it does NOT induce an immune response from the body (though that will happen anyway as the body mounts it's normal immune response to the virus)
- rootusrootus 7y agoSo it does not interfere with the body's own immune response, and in the end the patient should be immune in their own right (for however long that lasts)? Almost sounds too good to be true. I wonder what the real downside risks are.
- maxerickson 7y agoWe used to use horse serum to treat infections. Inject the horse with the disease and then filter the antibodies out of the blood. https://en.wikipedia.org/wiki/Antiserum https://en.wikipedia.org/wiki/Antiserum
- zaroth 7y agoIVIG is an extremely common treatment, used for immunocompromised patients, or sometimes after a stem cell transplant to bolster the immune system while it recovers. It’s not typically used in healthy adults as a way to treat a specific known pathogen because, well, we usually have much better options. Aside from being somewhat pricey, side effects are mild and it should be fairly effective.
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- Retric 7y agoWhile viable and potentially lifesaving, the risks associated with this type of treatment are significant and should not be downplayed. Edit: This is the line I am objecting to: “it can be used for prevention of infection for people who are being exposed or it could be used for therapy for those who are sick.” This is not something to generally be handing out to people after simple exposure. For one thing the benifit is short term.
- scotth 7y agoFor example?
- Retric 7y agoYou’re injecting blood products from another person so catching some other deadly disease is a real risk. Plasma is tested for AIDS and several other diseases, but prions for example are much harder to detect. Further, when you consider the risk of someone messing up on the supply side that opens up a host of issues.
- booi 7y agoThat’s why there is comprehensive screening of donated blood which has essentially eliminated pathogen transfer and it’s used en masse everyday.
- javagram 7y agoScreening is not perfect. https://www.redcrossblood.org/faq.html#eligibility-medicaltreatments https://www.redcrossblood.org/faq.html#eligibility-medicaltr... “ You may not donate if you received a blood transfusion since 1980 in the United Kingdom or France (The United Kingdom consists of the following countries: England, Wales, Scotland, Northern Ireland, Channel Islands, Isle of Man, Gibraltar or Falkland Islands). This requirement is related to concerns about variant CJD, or 'mad cow' disease.”
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- koolba 7y ago>> You're making sure that there are antibodies in there and that they would be effective? > Exactly. Exactly—that we have a potent unit. We think that one person can treat two people. Does this work in an ongoing chain? For example if person A’s plasma is used to treat B, can we take from B and treat C as well? Or does the quality of the anti-bodies depend purely on the immune system of the hose?
- zaroth 7y agoOnce someone has been exposed and recovered, they should have the antibody concentration required to be become a donor themselves. The required number of cells we’re taking about is high enough that you’re not transfusing A->B and then recovering A from B’s plasma and going on to give A->C. But while B is infected they will make their own antibodies and after they recover they could then be a donor as in B->C. As TFA mentions, China doesn’t even bother testing the level of antibodies, they just collect the plasma from anyone recovered. 90 tons to Italy... is a lot of plasma. At least for IVIG the plasma is pooled from a large number of donors for each transfusion ultimately given to a patient. So it’s more a question of the average antibody load than needing to gauge each individual donor’s levels. > Each IVIG preparation is made from the pooled plasma of 3,000-10,000 blood donors, which is then purified to contain more than 90% antibodies. [1] I think we need to start collecting plasma from recovered positive cases today. I get that for a trial you do want to have a measured baseline of antibodies. But we can start stockpiling and pooling COVID antibody plasma even without the antibody testing. [1] - https://www.rheumaderm-society.org/ivig/ https://www.rheumaderm-society.org/ivig/
- rsfern 7y agoFormal writeup here: https://www.jci.org/articles/view/138003 https://www.jci.org/articles/view/138003 Edit: lots of interesting details. a couple takeaways: 1. “Depending on the antibody amount and composition, the protection conferred by the transferred immunoglobulin can last from weeks to months.” 2. One of the proposed deployments is to protect frontline health care workers from infection (and remove their need to quarantine) until a vaccine can be developed 3. This treatment was apparently used for quite a few other outbreaks, including the 1918 flu epidemic, MERS, and there is a report of it being used against the novel Coronavirus in China
- koheripbal 7y agoIt's really only a solution for healthcare workers due to the amount of work required to harvest and transfer immunoglobulin. I think a far more scalable solution for the general public is the use of existing anti-viral drugs.
- stjohnswarts 7y agoI don't see why people think we will hold out 18 months for a vaccine to be developed and tested, society would fall apart by then. I don't see it lasting longer than 2-3 months quarantine and then the common people will just go out anyway, especially in the USA where there's not much of a safety net.
- ltbarcly3 7y agoThere won't be a safety net anywhere if they require everyone to be quarantined for 18 months. The government can print money by changing a number in a computer, but they can't print sandwiches that way. Eventually dumping money into the economy where very little is being produced just leads to runaway inflation.
- matwood 7y agoI don't think anyone is expecting an 18 month quarantine (and no country in the world has a safety net for people to sit home for 18 months). I expect 2-4 weeks at best in an attempt to 'flatten the curve', and then isolation of vulnerable population going forward. The spread will also slow as more and more people have the mild version and can no longer be a vector.
- _bxg1 7y agoThis crisis is the first event in my lifetime that's given me any optimism about our ability, as a global civilization, to solve problems and get things done. I don't feel like we've seen humanity at its best in several decades. Shame it always takes a catastrophe (and an immediate one at that; see climate change) to bring it out.
- captainbland 7y agoI think it is basically inevitable that a cure/vaccine will be found. That's not to downplay it, obviously the teams involved will deserve huge congratulations and will have done something great and it is badly needed. But the real test is how we handle it until that cure/vaccine becomes available, which is certainly something that a lot of places are struggling with, particularly here in the UK where we spent weeks spectating on our neighbours struggling with it and racking up deaths (particularly in Italy) before realising that exponential growth also works here.
- ehsankia 7y agoI think it has the potential to, but so far, there hasn't really much of it, or have I been missing it? Obviously progress is slow, but I think there's also a lot of fluff being thrown around, so we won't really know for some time. I haven't noticed any extra amount of cooperation though between countries, more so than the usual.
- _bxg1 7y agoI guess I primarily mean the people on the ground. Not the politicians - the best that can be said about them is that they're getting out of the way (in some, not all cases) - but the doctors and nurses, the scientists, the grocery store workers, the companies converting their factories to make medical supplies, and yes, even the bureaucrats who are pushing this stuff through. There are still lots of people out there to be disappointed in, but we're also seeing those who do care about the greater good coming out of the woodwork and really taking real action, and it's inspiring.
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- tcbawo 7y agoSome emerging theories of pathology suggest that lung function can be increased by reinflating collapsed alveoli with constant pressure: https://emcrit.org/pulmcrit/cpap-covid/ https://emcrit.org/pulmcrit/cpap-covid/. It describes cases where oxygen supplementation could be reduced or eliminated. This development (https://www.isinnova.it/easy-covid19-eng/ https://www.isinnova.it/easy-covid19-eng/) looks very promising for 'sub-intensive' cases -- adapting decathlon mask/snorkel with a 3D printed valve to provide positive air pressure (to help reinflate lungs) without intubation or leaking contaminated exhaust. If the closed mask method could be used successfully to prevent serious cases from progressing to ICU (or more importantly, keep people in their homes a little longer), it could have a huge impact on reducing load in the hospital system.
- agumonkey 7y agoI don't know where to ask.. is vaporized cbd helpful ? it's said to be a potent anti inflammatory compounds and also help cleansing cells through apoptosis.
- DrAwdeOccarim 7y agoI doubt it, though I don't have any references. Do you have any peer reviewed papers on CBD and lung function?
- agumonkey 7y agoI'm not on my laptop but the are a few studies on cannabinoids and lung tissue. I'll edit this later
- jeltz 7y agoI am not a doctor but if it is indeed anti-inflammatory and causes apoptosis it sounds more likely to be harmful than to be helpful. I suspect apoptosis (or rather what happens is that cells get hijacked by the virus and then the immune systems kills the hijacked cells) is what causes most of the lung damage and inflammation is an important part of the response from the immune system so I would not mess with that more than necessary.
- ltbarcly3 7y agoWhy do they keep saying 'until vaccines are ready' as though it's a foregone conclusion that we can make a vaccine for this? Is this type of virus always a good one to make vaccines for? There are tons of viruses we have failed to vaccinate for, despite trying for 30 or 40 years. People seem to be universally saying a vaccine is '12-18 months away'. Is this just misinformation? I would love to hear from an expert about this.
- dmarchand90 7y agoNot an expert. It's not guaranteed but it seems like covid19 has a lowish mutation rate, similar or perhaps lower than the flu. So it would seem reasonable that this a vaccine-amenable virus. But there are no guarantees.
- funcDropShadow 7y agoBecause, there are multiple teams of companies and scientists around the globe, that all report that they'll have candidates ready in the very near future, i.e. 3-4 weeks. Which means they are convinced the vaccines work. But since vaccines are given to a large number of people, you have to make sure that there is a very low number of adverse effects. And that takes most of the time. But the vaccine candidates are almost ready.
- oli5679 7y agoThis thread is quite encouraging. Argues that reason why we don't have one for other coronaviruses is because of cost-benefit not high enough, rather than technical hurdles. 20% colds caused by 4 different Coronaviruses, so hard to justify making a vaccine that reduces cold risk by a few %. Agree that there is uncertainty though. "Covid is so technically doable we already have vaccines for dog & cow coronaviruses. We’ll definitely make one for covid, trials will be simple since we’ll be specifically trying to prevent Covid, which is only caused by SARS-CoV-2 (not by dozen different viruses)" https://twitter.com/PeterKolchinsky/status/1240498037958545410 https://twitter.com/PeterKolchinsky/status/12404980379585454...
- ekianjo 7y agoWhy this article does not mention chloroquine at all, though?
- tyingq 7y ago"Yes. In fact, the Chinese sent 90 tons of plasma to Italy." That's impressive. I wonder how many individual donations that maps to. And how many people that could treat. Edit: Trying to answer my own question. Typical blood donation is 470ml. That weighs about 0.5 kilograms. Plasma is roughly half of what's in your blood, so half that again... 0.25 kilograms. So assuming they meant metric ton (1000Kg), 4000 individual donations per ton. 90 tons is then 360,000 donations. Did I miss some math? That's, um...wow. Maybe the 90 tons includes bags, boxes, pallets, etc? No idea how many that treats though.
- funcDropShadow 7y agoThere don't exist 360.000 recovered humans at the moment. At least officially.
- tyingq 7y agoYeah, that's why I keep looking at my math, though it seems straightforward. That 90 tons must be off somehow.
- DigitalSea 7y agoPresumably, they also have to keep the plasma cool, I am guessing some of that 90-tonne wait could be attributed to cooling gels/liquids of some kind to keep it stable for transport. Admittedly, I don't know how they would even transport this over long distances like that.
- saalweachter 7y agoHmmm, Googling seems to indicate that private donation centers in the US allow donations twice a week. Multiple donations per donor?
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- tomohawk 7y ago> clinical trials could begin in 3–4 weeks provided that they clear all the regulatory steps. If that happens ... Can someone break this down day by day as to why 3-4 weeks are necessary and proper to get through the very first regulatory hurdle?
- alok-g 7y agoDoes someone know how much of this needs to be injected to be effective?
- samsonradu 7y agoMy knowledge about industrial manufacturing is slim to none so can someone explain please why is it not possible to (globally) ramp up production of face masks and ventilators to a virtually unlimited quantity? What exactly is the bottleneck? Are we lacking materials, labour or the technical know-how? Are the factories currently producing them so advanced and hard to reproduce?
- raverbashing 7y agoI think you can ramp production of those but it will still require people to work them and the most severe cases are still fatal even with the ventilators.
- samsonradu 7y agoWell, there is no silver bullet here is it? If we're to solve this we'll probably need to tackle it from all sides - isolation, vaccine and treatment.
- throwaway_pdp09 7y agoAKA there's no 100% guarantee for anything. Your point being what?
- raverbashing 7y agoMy point is that you don't need to scale production of ventilators beyond the capacity of the medical system of deploying them.
- fulafel 7y agoSame as many other problems (eg global warming) - the market economy can't deliver a solution because it's not short teem profitable for the relevant actors.
- lotsofpulp 7y agoIt could be priced to be short term profitable, but then the sellers would get accused of price gouging.
- rurban 7y agoAntivirals are ready. HCQ was mass produced for decades, and ramping it up is trivial, and already done. The first vaccines, BGM, will be ready in summer. This was already applied en masse in the UK in the 60ies, and is in stage 3 testing. What else: Vitamin C is ready. Self made masks are better than no masks. Ramping up tests kits are the most important part until summer. There's a new faster one in testing, which needs 20min, and will cost €15. Contact-less thermometers can be imported en masse from China. Creating antibodies from plasma is not really viable for billions. The rest is.
- Jemm 7y agoProblem with vaccines is that there is as yet no evidence that humans develop immunity to COVID-19. No immunity, no vaccine. Hopefully that changes soon.
- AntonStratiev 7y agohttps://twitter.com/NAChristakis/status/1240689935557865472 https://twitter.com/NAChristakis/status/1240689935557865472 Details a study on a different Coronavirus in 1990. There is definitely some immunity, but its complicated.
- cleeus 7y agoChina now has a lot of donors for plasma with antibodies. That's why they can stop the shutdown and start tracing outbreaks and treating patients.
- znpy 7y agoDumb question: infusing someone with antibodies-containing plasma from a recovered patient will help the receiver develop their own antibodies ?
- tmalsburg2 7y agoChina sent 90 tons of plasma to Italy? I don't understand. A ton is 1000 liters. A single blood donation is usually 500ml , not sure how much plasma that would produce. But this means that they had at least 180K donations which seem implausible. Could someone please explain?
- Guidii 7y agoPerhaps the plasma is packaged? I'd expect there'd be a fair amount (20-50%?) of non-plasma in those 90 tons.
- woadwarrior01 7y agoI’m going out on a limb here. One possibility would be mandatory blood donations at “re-education” camps and prisons.
- snehapa 7y ago21 days lock down the best prevention. However, In India, the train and other transport and the PM said to make a 21 days lockdown. I think its the best preventive measure. Look at the report what will be the situation if the public transport works under this condition. https://quintdaily.com/2020/03/train-services-stopped-due-to-corona-outbreak/ https://quintdaily.com/2020/03/train-services-stopped-due-to... Even though, not only the government can only prevent this issue. Self-protection by taking care of their business for some days, until this issue get into a stable position is also the right choice. My suggestion as my thought by checking with my doctor's circle is that: Preventive medicines for Ebola, Polio Vaccines that gives under age of 10 can be a better solution to stop far away virus issue.
- arjunvr54 7y agoVaccines should be the better idea rather go behind launching tons of ventilators. Even there were people not educated and still not care about the issues. For those people antivirals don't be the right choice, looks like vaccines are the best prevention - Early vaccines. How about trying the Ebola vaccines - I think that can be a preventive measure right.?