Timeline Scenarios for Vaccine Development
May 1, 2020 8:54 AM   Subscribe

How Long Will it Really Take to Develop a Covid-19 Vaccine? "Our record for developing an entirely new vaccine is at least four years — more time than the public or the economy can tolerate social-distancing orders. But if there was any time to fast-track a vaccine, it is now. So Times Opinion asked vaccine experts how we could condense the timeline and get a vaccine in the next few months instead of years." The timelines charted in the article show the consequences of telescoping the development schedule by compressing academic research times, starting trials early, using concurrent Phase trialing, building factories before vaccines are proven effective, and fast-tracking FDA approval.
posted by storybored (98 comments total) 38 users marked this as a favorite
 
I read this article this morning right when I woke up and it's crushed me for the whole day. I think it's right, and realistic, and also awful.

I am very, very angry that the US government has no plan to fight Covid-19. All we seem to have is "keep it spreading slowly and wait for a vaccine". But if a vaccine is 1-20 years away, time really unknown, that is not tenable. Even 12-18 months of waiting for a vaccine is going to be devastating: on health, or the economy, or both.

Meanwhile, civilized countries like South Korea and Germany and New Zealand are implementing plans. They are testing people. They are tracing contacts. We could do that in the US too. Estimates are it'd take 300,000 people to contact trace America (based on a 1:1000 ratio). But no one is going to do that. The federal government is doing very little to staff up contact tracing. If you add up all the states' efforts, we're going to get maybe 35,000 eventually. 10% of what we need.

I was hopeful we could at least have a meaningful plan in California. But we're going very slow and not thinking big enough. We're talking about 10,000 tracers, far short of the 40,000 a 1:1000 ratio requires.

America has failed this test. We'll be paying the consequences for years.
posted by Nelson at 9:32 AM on May 1 [47 favorites]


Everyone is talking about vaccines, but is there any chance an effective treatment could be developed sooner? Not a cure-all, but something to alleviate/shorten symptoms and keep more people out of hospitals, bringing Covid-19 back to "just like the flu" risks, or closer to it? Or is that even more difficult than developing a vaccine?

I don't know anything about medicine or science and am sure I'm wrong, but was just wondering if this would be more/less feasible than a vaccine to get us back to having a Society again.
posted by windbox at 9:58 AM on May 1 [5 favorites]




Everyone is talking about vaccines, but is there any chance an effective treatment could be developed sooner? Not a cure-all, but something to alleviate/shorten symptoms and keep more people out of hospitals, bringing Covid-19 back to "just like the flu" risks, or closer to it? Or is that even more difficult than developing a vaccine?

One of the first people I read about in Washington recovering from COVID-19 was treated with this stuff, and that was over a month ago.

It already exists, it has one US manufacturer, there are no generics.

Murica.
posted by deadaluspark at 10:08 AM on May 1 [4 favorites]


I wish I hadn't read this when I have 6 more hours of work to go through because I want to cry yet again.
posted by jenfullmoon at 10:13 AM on May 1 [2 favorites]


I hope more people read this, because this is why I had my freakout about this shit early on. About a month ago I was realizing that this shit was not going away anytime soon and anyone who thought different was deluding themselves and not facing reality.

Yes, tears are appropriate, because most of us here live in a country where there is literally no plan to face this, because we would rather let people die than let capitalism suffer or consider another option than capitalism.

The Greatest Depression is upon us.
posted by deadaluspark at 10:16 AM on May 1 [30 favorites]






something to alleviate/shorten symptoms and keep more people out of hospitals, bringing Covid-19 back to "just like the flu" risks, or closer to it?

There are lots of studies underway, including some proper randomized controlled trials. Results from those better studies will start coming in over the next few months. Some of studies are "throw it at the wall and see what sticks" of approved drugs with low(-ish) side-effect profiles, on the theory that it can't hurt to try, you can go straight to a study of human efficacy because safety is already established, and there's already production capacity for those drugs. This is the theory behind, e.g, studying the heartburn drug famotidine.

Several hospitals are trialling plasma from recovered patients. This is a very plausible treatment, but there are lots of limitations. There are limits to how much can be produced (only so many donors available and they can only donate so often), it's expensive to transport from where it's available to where it's needed, it can't really be self-administered, etc.
posted by jedicus at 10:26 AM on May 1 [5 favorites]


To the question about treatments above: there are numerous treatment trials underway as well, of widely varying quality of course. TheSOLIDARITY trial from WHO is a very cleverly designed study to allow international participation and study the 4 most promising existing drugs. Just like with vaccines, we don't know how long it will take to find effective treatments. (Remdesivir, also mentioned above, is one drug being tested. We currently have little meaningful evidence of its efficacy)
posted by latkes at 10:31 AM on May 1 [5 favorites]


Everyone is talking about vaccines, but is there any chance an effective treatment could be developed sooner? Not a cure-all, but something to alleviate/shorten symptoms and keep more people out of hospitals, bringing Covid-19 back to "just like the flu" risks, or closer to it? Or is that even more difficult than developing a vaccine?

From the article, this link shows 254 therapeutics in development. Plus, what I'm reading and hearing from lot of health-care workers about the current hellscape: with every patient they treat, regardless of the outcome, they're learning about what works and what doesn't work, and with every passing day we understand the virus (even if it's knowing what we don't know) a little better. Those anecdotes, plus expanded hospital capacity, are reasons for optimism. If they live in an area with resources, a person's chances of making a good recovery are a lot better in May 2020 than they were in March 2020.
posted by witchen at 10:32 AM on May 1 [7 favorites]


It already exists, it has one US manufacturer, there are no generics.

One thing of which I am very certain is that if -- and it is still "if", because there's still no randomized controlled trial of remdesivir, nor any large study -- remdesivir turns out to be useful in controlling symptoms, no other country is going to respect their patent on it. They'll either nationalize it outright or just copy it and weather the lawsuit another day.
posted by The Pluto Gangsta at 10:34 AM on May 1 [20 favorites]


My adult (40) nephew is in jail. Again. Drug charges, parole violation, etc. His fault, I get it. But this last time he's been in, he's now been diagnosed with Coronavirus—twice... he's due to be out, but they won't let him go. I don't know all the details, but he has nowhere to live, so he's trapped in jail. He's not had super-horrible symptoms, but still. His mom is trying her best to get him out, but she doesn't have any big resources, she's not a very high-functioning person in many ways herself. She's even contacting news stations. It's a goddamned mess. I'm sure the prison system is more messed up with this than any of us could know. His girlfriend/daughter's-mother wants him out but doesn't want him living with her and her 5 kids. She's barely making ends meet. She's still working but barely.

That's a face of Covid-19. The little people are taking it on the chin—again—and until there's a vaccine/cure this is going to be a slow motion train wreck of unprecedented magnitude. I'm so fucking angry. But all we are seeing is little snapshots in time... we won't know anything about this for years. Our entire system (government, media, social) is unprepared for a disaster this long-term, this ongoing. My sense is we are still in the very beginning.
posted by SoberHighland at 10:44 AM on May 1 [31 favorites]


According to Wikipedia the limited trials of remdesivir so far have shown little to no positive effects and troubling side-effects.
posted by sjswitzer at 10:51 AM on May 1 [2 favorites]


This is mentioned, specifically in relation to HIV treatment, where we have yet to develop a working vaccine, but do have effective treatment options after years of research.
posted by snofoam at 10:57 AM on May 1 [2 favorites]


And, crucially, we also have PrEP, an effective HIV preventative.
posted by sjswitzer at 11:00 AM on May 1 [2 favorites]


Well that was a depressing reality check. Damn.
posted by lazaruslong at 11:05 AM on May 1


Fauci was in the news yesterday talking about a vaccine by January. It sounds like they're planning on a hail Mary sort of effort to run flat out to a vaccine, like in the movie Contagion. It's a classic America strategy of trying to beat nature with brute technology. Meanwhile, Vietnam has managed to control this thing at least as well as we have. Vietnam!

Even if the vaccine works, failing to pour federal billions into testing and tracing is just deciding that it's fine to let tens of thousands more die before then. And we know that such an effort would help, immediately. Right now. Not months from now.
posted by BungaDunga at 11:08 AM on May 1 [14 favorites]


It's possible we will develop a synthetic antibody treatment, which might both act as prophylaxis and cure. There's one for Ebola, and it works well. They're expensive and take a long time, but it may be that we have a working artificial antibody before a vaccine.
posted by BungaDunga at 11:14 AM on May 1 [4 favorites]


As I scan the report on possible drug therapies, I often see the phrase "prevention and treatment." But I suspect that prevention and treatment may be two very different problems. Prevention will involve preventing the virus from taking hold or muting its effects. Treatment will mean dealing with the body's runaway immune response, among other things.

To make this point absurd, nobody expects ventilators to prevent COVID-19. And an eventual vaccine will be of little to no use when you're already ill.

I have seen reports of efforts to identify drugs (or vaccines) that people are already taking that seem to reduce incidence. For instance, the TB vaccine BCG is being looked at since there are indications it may have some preventative effect.

But retrospective studies like that require a lot of data that we don't really have yet. We hardly have a grasp on how many people get infected but never get seriously ill.

Nevertheless, it appears to me--though this could just be where the media is focussing--that the bulk of the effort is on treatment, as it should be at this acute stage of the epidemic. I wish I were confident that researchers are quietly investigating preventative measures with sufficient urgency and resources.
posted by sjswitzer at 11:15 AM on May 1 [1 favorite]


Along those lines, while the tide has turned on mask usage in the US, it would be nice to know if mask usage (and what kind of mask usage) would be sufficient to drive R low enough that talking mass transit to work is "safe." Maybe it is or can be, but I don't think we really know that yet.

Just knowing what measures actually do make it safe to work, shop and travel could go a long way toward getting this thing under control. And since it's all we have for now and the foreseeable future I hope we're making progress on that.
posted by sjswitzer at 11:23 AM on May 1


This link goes into the regulatory reasons why a vaccine may take time to develop, less about the virus. Dr. David States wrote a pretty decent Twitter thread explaining a bit more about the technical difficulties around vaccine development, as it relates to the virus itself.

According to Wikipedia the limited trials of remdesivir so far have shown little to no positive effects

Apparently there can be some improvement of symptoms with remdesivir.

There is also an early paper out in Nature where researchers did parallelized trials of existing drugs — some of which have known safety profiles and are approved, and so can be repurposed quickly:
In this study, we have identified 332 high-confidence SARS-CoV-2-human PPIs connected to multiple biological processes, including protein trafficking, translation, transcription and ubiquitination regulation. Against these targets we found 69 ligands, including FDA approved drugs, compounds in clinical trials, and preclinical compounds. Antiviral tests in two different laboratories reveal two broad sets of active drugs and compounds; those impinging on translation, and those modulating Sigma1 and Sigma2 receptors. Within these sets are at least five targets and over ten different chemotypes, suggesting a rich landscape for optimization.
Even without a vaccine at the ready, we may be able to find antivirals in the meantime, which can help give us time to treat infections and get public policy to ramp up social distancing and contact tracing.

We're also seeing fast improvements in vaccine technology — there are trials of mRNA vaccines underway here in Seattle, for instance. Their advantage lies in the ability to ramp up vaccine production quickly and cheaply, key factors for making them usable.

It's early days and I don't think pessimism is warranted until we know more about this virus. Trump and his accomplices failed us, but we can — and will — use science to fight back and get people healthy again.
posted by They sucked his brains out! at 11:26 AM on May 1 [11 favorites]


Just knowing what measures actually do make it safe to work, shop and travel could go a long way toward getting this thing under control.

Sometimes it might be better just to adopt a measure even if we don't know for sure if it works well or not, if that measure seems reasonable and is of relatively low cost.

Masks fall into that category, it seems. They reduce droplet spread which is the known major vector for infection. How much? We don't know. But if even a simple paper mask makes a small reduction, that cost would be worth it.
posted by storybored at 11:31 AM on May 1 [1 favorite]


The country is currently hiring about 600K-700K workers to conduct Census 2020. We need about half that for contact tracing the entire country.
posted by RobotVoodooPower at 11:35 AM on May 1 [8 favorites]


Scott Griffin at TWIV says remdesiver studies are in conflict. Additionally, the most effective timeframe for antiviral therapies is within the first few days of infection.

So (if the drug is even useful), everyone who is in early phases is being sent home to ride it out until it gets bad - not admitted and put on IV remdesivir.

Antivirals are not as good as vaccines.
posted by j_curiouser at 11:39 AM on May 1 [8 favorites]



My adult (40) nephew is in jail. Again. Drug charges, parole violation, etc. His fault, I get it.


My wife is up for jury duty next fall. Let's just say if there's a risk of a de facto death penalty for minor offenses on account of Covid, some of us will be harboring in our minds a much more stringent definition of certainty beyond a reasonable doubt when we get empaneled.
posted by ocschwar at 11:43 AM on May 1 [21 favorites]


(Bill) Gates' notes on how long it'll take to get a vaccine (posted yesterday) is a another look at the question, as well as additional background on the RNA-based approach, and imo has a bit more of a positive outlook.

One thing that's fascinating (to me) is to conceptualize the sheer scale involved. Hand-waving that the vaccine exists and that we're able to manufacture it in quantity, there's still the issue of how on Earth to distribute 7-billion (or so) of something. At a rate of 1 shot a second, that would take 221 years!
posted by fragmede at 11:45 AM on May 1 [5 favorites]


Oh yes, certainly masks are helpful and people should use them! Sorry if I seemed to be implying otherwise.

What I'm looking for is more research on effective mask usage, I mean surely we'll want to be using the right kinds of masks in the best way that is possible/practical.

And I'm also hoping there'll be a point where we know whether they're effective enough to get on a subway with confidence. It may well be that they are, and it would be really nice to know that. Also, procedures for office workers... how to hold meetings, etc. None of these things require any new drugs and all of them could be effective.
posted by sjswitzer at 11:48 AM on May 1


there's still the issue of how on Earth to distribute 7-billion (or so) of something

McDonald's manages to sell ~2.3 billion burgers every year, which involves quite a lot of supply chain logistics. It's certainly complicated, but doable.
posted by jedicus at 11:50 AM on May 1 [10 favorites]


It's possible we will develop a synthetic antibody treatment, which might both act as prophylaxis and cure. There's one for Ebola, and it works well. They're expensive and take a long time, but it may be that we have a working artificial antibody before a vaccine.

Probably the closest analogue in routine use in North America is palivizumab, aka Synagis, a monoclonal antibody against respiratory syncytial virus (RSV) which causes bronchiolitis, a pneumonia-like illness in infants and small children.

The main thing it’s good for us reducing hospital admissions, which it does by 50-60%. It doesn’t reduce infectivity, may or may not reduce overall mortality, requires a monthly injection, can have serious side effects, and costs a fortune. It’s only used for high-risk patients (preemies, babies with heart or lung problems) because they’re the ones likeliest to do badly if they get RSV.

So if we get a monoclonal antibody for COVID, it’s likely to be the same sort of situation: possibly helpful on the individual level but probably not on the public health level.
posted by saturday_morning at 11:55 AM on May 1 [7 favorites]


In winters past, when I've had some variation of the flu, I've been told that it's not bacterial so there's nothing we can do. While it's still true that antibiotics won't do anything for a viral infection, it's been news to me that there are anti-virals that exist and could be used to reduce the viral infection. I'm not sure how I feel, that I've never been offered them (well, Tamiflu) to reduce the duration and intensity of the flu. FWIW, I have been offered, and taken, the flu vaccine.
posted by fragmede at 11:56 AM on May 1


The thing about Tamiflu is that you have to take it really really quickly for it to have any meaningful effect. If you wait to see the doctor until you've felt sick for a bit it's essentially too late. (This isn't directed at you fragmede, just general info.)
posted by Justinian at 11:59 AM on May 1 [4 favorites]


The story last week about remdesivir was that it (maybe) helps during recovery, and that it's not effective for people in COVID's upswing.
posted by rhizome at 12:03 PM on May 1


I asked for and got Tamiflu within 24 hours of getting flu A this winter (I only knew I should get tested for flu A because my son had it too). I woke up the second morning with a 103 fever and within an hour of the morning Tamiflu dose, it was down to 99, so I think it definitely did something. I was definitely less sick than when I had the flu 15 years ago, although maybe that was also because I'd had a flu shot this season.

But if we're just telling everyone with COVID to go home until they can't breathe, how could a treatment like this help anyone?
posted by Ralston McTodd at 12:03 PM on May 1 [6 favorites]


Antivirals are not as good as vaccines.

The medications in PrEP are real-world examples of antivirals proving as useful as a vaccine, insofar as 1) they and other ART and prophylactic antivirals are reducing HIV-1 infection numbers, and 2) we have no vaccine for HIV-1. Some public health entities are working to make them available easily and at very low or no cost. It seems like there is a place for them in public health policy, for lack of a vaccine.
posted by They sucked his brains out! at 12:13 PM on May 1 [12 favorites]


I don't know all the details, but he has nowhere to live, so he's trapped in jail.

This is what I keep wondering about with regards to "we have to get people out of prisons or they'll get it." If they have nowhere to go and will be homeless when they are let out, how much of an improvement is that?
posted by jenfullmoon at 12:22 PM on May 1 [5 favorites]


Unfortunately prisons often won't release people who don't have an address to go to. Causing them to have to serve their parole inside, for the crime of being homeless. Some society we have.
posted by tiny frying pan at 12:32 PM on May 1 [9 favorites]


I read that Remdesivir is only available as an IV treatment. Doesn't that complicate trials? I one needs to be admitted for a treatment when only space for the worst cases, testing if it's helpful in the early stages of the illness is logistically complicated.
posted by sammyo at 12:38 PM on May 1 [1 favorite]


Yes, Remdesivir is an IV treatment so dosing prophylactically is troublesome.

That Nature paper with drug repurposing is full of unwarranted hope. Interrupting cellular processes that the virus depends on is usually fairly toxic. Sometimes you can make a drug on that basis but rarely. Those pathways exist elsewhere and your body won't appreciate them being shut off. Do not trust in vitro assays at all for proof of efficacy. If in vitro cellular assays were all that was needed to find drugs we would have cured every disease by now. The hard part is finding drugs that can get to the right place and concentration in your body without killing you in the process.

I'd use HIV timelines for drug development as a pessimistic view of how long it takes to get very safe prophylactic antivirals (at least a few years).
posted by benzenedream at 12:51 PM on May 1 [11 favorites]


Remdesivir is only for hospitalized patients and is actively being studied and as yet lacks enough evidence for anyone, least of all us non specialists on metafilter, but also even specialists, to draw meaningful conclusions about. Headlines are bad folks.
posted by latkes at 12:57 PM on May 1 [7 favorites]




Remdesivir is only for hospitalized patients and is actively being studied and as yet lacks enough evidence for anyone, least of all us non specialists on metafilter, but also even specialists, to draw meaningful conclusions about.

Every time I hear anybody say anything about any drug being a potential treatment, I just want to yell, "YOU DON'T KNOW THAT, SHUT THE FUCK UP". Last week it was something about famotidine. This week it's remdesivir, and honestly I thought Dr. Fauci of all fucking people would know better. I'm just so goddamned furious at all these irresponsible assholes right now.
posted by tobascodagama at 1:29 PM on May 1 [5 favorites]


There was a decent Twitter thread on the difficulties of a vaccine.

On Reddit a lot of people seem to be expecting a super-effective vaccine within months, they excitedly post every optimistic estimate from a VC firm.

Another thing is that even if there is a vaccine it may well be like the flu jab: something that's partially effective and just reduces your chances of getting the virus.

A lot of people seem to expect The Vaccine to not just be super-fast, but also super-safe and super-effective.
posted by TheophileEscargot at 1:39 PM on May 1 [4 favorites]


honestly I thought Dr. Fauci of all fucking people would know better. I'm just so goddamned furious at all these irresponsible assholes right now.

Fauci doesn't work at the FDA. Also, Fauci spent a good portion of his career getting death threats for having the exact view of experimental medicine as you think he should have.
posted by sideshow at 2:01 PM on May 1 [7 favorites]


Radio NZ ran a discussion with several NZ and Australian virologists a couple of days ago, I heard most of it (reasoned and clear, worth a lioster, 54mins). It's focus is whether NZ should at least try to develop a vaccine, because the world doesn't even know we exist - reddit-MapsWithoutNZ - so we'll be very last in the queue.

It was pessimistic about a short time-frame and the need to be very realistic.
posted by unearthed at 2:03 PM on May 1 [4 favorites]


I keep telling people: If we have the Perfect Anti-COVID-19 Drug today, it will take over a year for that to be verified, and another several months (at best) to be put into widespread use.

We do not, however, have the Perfect Anti-COVID-19 Drug today. And we are not likely to find or make one in the next year, because most "find a medicine" processes aren't "by pure luck, the third compound they put in the petri dish worked perfectly." Instead, the early results with some useful effects (but not enough, or not on a wide enough range of patients, or with too many side effects) get adjusted and the new version goes through the same process.

And in the meantime, sigh, we're going to have a whole lot of "X treatment works somewhat, on patients with some of the symptoms," followed by "we have the PAC19D so let's make a few hundred million doses of it and get it to everyone NOW!!!!"

...Chickenpox vaccine took 40 years to be licensed in the US. Flu vaccines take 5-6 months to develop and distribute after the new strain is identified. Effective AIDS treatment in the US took more than 8 years after the President admitted it was a big problem (...ignoring the first 5-8 years of buildup).

Even with enthusiastic gov't support and a whole lot of money, research just doesn't move that fast.

There is no going back to business-as-usual as we had at the beginning of 2020. (Which. Ahh. May be the first time since November 2016 that I've even thought the concept of "business as usual" for what's been going on in the US.) If we get The Perfect Vaccine ready for widespread distribution in a year - which would take more than one miracle - society will have been permanently altered.

We need to figure out which alterations we want to keep around.
posted by ErisLordFreedom at 2:10 PM on May 1 [16 favorites]


Every time I hear anybody say anything about any drug being a potential treatment, I just want to yell, "YOU DON'T KNOW THAT, SHUT THE FUCK UP". Last week it was something about famotidine. This week it's remdesivir, and honestly I thought Dr. Fauci of all fucking people would know better. I'm just so goddamned furious at all these irresponsible assholes right now.

I mean, it's not a perfect study by any means, but a reduction of mortality by 3.6 percentage points, with p=0.059, is actually really promising at this stage of research. Whether or not this will really pan out in the long term, the other result, of 31% faster recovery time, p<0.001, is extremely important from a public health perspective of not overloading hospitals.

I'm not big on the 24 hour news cycle and all the fake science being dredged up, but honestly this looks very likely to be mildly helpful, and I have a hard time getting mad about people enjoying a bit of probably-good news right now.
posted by thegears at 2:12 PM on May 1 [9 favorites]


I mean, it's not a perfect study by any means, but a reduction of mortality by 3.6 percentage points, with p=0.059, is actually really promising at this stage of research.

Sure, it's promising! There's another study from China that did not show improvement though, and even this study did not show statistical significance in mortality difference between the placebo and drug arms. Soo.. yes, exciting possiblity! I am all for people feeling optimistic! Please do so! But be cautious of the impact of spreading a false sense that we already have an established effective treatment. This leads to all kinds of hijinx that can ultimately impact medical practice and policy in a dangerous way. But I hope we continue to see more research showing the efficacy of this drug!
posted by latkes at 2:51 PM on May 1 [2 favorites]




Vietnam has managed to control this thing at least as well as we have. Vietnam!


Woah you're underselling what Vietnam has done, by like several orders of magnitude. Vietnam has started easing restrictions - they've beaten the virus with just 270 infections and 0 deaths, which is remarkable for a nation of 97 million people who share a border with China and was the site of the first mass outbreak outside of China. LA Times link, summary below.

---

American officials have been struck by Vietnam’s low infection rate. Experts from the U.S. Centers for Disease Control and Prevention in Vietnam — who have provided assistance in testing, data analysis and contact tracing — say they “don’t have any indication that those numbers are false,”

---

“Only a few countries can control and mobilize resources on this scale,” said Le Hong Hiep, a Vietnam analyst at the ISEAS-Yusof Ishak Institute in Singapore. “In Vietnam they can do it, and partly because of a political system that’s designed to respond to such situations. It’s not always good, but in a crisis it helps.”

---

My own thoughts - it's nearly impossible to separate fact from fiction nowadays. Ultimately public opinion is becoming a worthless currency: you can always manipulate it if you control the media narrative, after all. In the end the only thing that matters is power: if a nation can safeguard its health system, and its most important resource - its people - it will grow stronger - and through history, the strongest survive. Who knows - Covid has a relatively mild fatality rate, but it's reassuring that some countries are able to rapidly deal with a pandemic. If the world ever gets hit by a super disease at least we will know some nations will survive
posted by xdvesper at 7:16 PM on May 1 [7 favorites]


It's my understanding that this coronavirus is like most others - it mutates, albeit slowly, so - even if we get a vaccine in a year, that vaccine may only last another year. This may well be the rest of our lives.
posted by Dashy at 11:49 PM on May 1




It's my understanding that this coronavirus is like most others - it mutates, albeit slowly, so - even if we get a vaccine in a year, that vaccine may only last another year. This may well be the rest of our lives.

I would guess that once they have one working vaccine they will be able to roll out updated versions like flu shots. I think it's fairly plausible that this thing won't go away entirely, though, but rather become a more controllable episodic disease.
posted by atoxyl at 2:55 AM on May 2 [4 favorites]


-variolation?
-convalescent plasma therapy?


I think the problem with that is that using both at once is that it's working with two moving targets. Antibody affinity can vary from person to person. That's why CP doses are usually pretty damn huge (200mL of the stuff) since the object is to neutralize as many antigens as possible to give the person the biggest chance they have of survival. Even with CP therapy, it still relies on the immune system to continue ramping up to finish the job since cytotoxic cells and phagocytes are still required to clean up the mess.

If one uses variolation and is given a CP that's too good the immune system may not be challenged. If one is given a CP that has a poor affinity the virus may end up running rampant and it might turn into a full blown infection anyway.

I personally think the fastest and most effective treatment is going to come from CP until monoclonal antibody mass production gets into gear (this will be months but far faster than a vaccine, mAbs can be produced en masse EXTREMELY quickly once the production line is fully operational) and will probably buy us time until a vaccine. Infection won't be stopped but an mAb will let us basically give an injection and then the severity of the infection should immediately start to decline making survival rates much higher.

Vir Biotech, Regeneron, and AbCellera are all using their tech to try and sort through the masses (trillions) of antibodies trying to find the most effective and highest affinity antibodies they can. Most of them are scheduled to start human trials in the summer. I believe Vir is also trying to alter the antibodies to last longer in the blood which will make them a good candidate for prophylaxis and would act almost like a limited vaccine. The problem is that mAb cannot be administered orally so administration would stretch the healthcare system. AbCellera is using some insane machine learning tech to sort through the trillions of antibodies more quickly than ever before. Once they have their candidates they're going to pass them off to Eli Lilly to bring their massive resources to bear.

I'm kind of hopeful that this will be the turning point in the fight until the rest of the medical industry can finish the job.
posted by Your Childhood Pet Rock at 6:35 AM on May 2 [6 favorites]


I would guess that once they have one working vaccine they will be able to roll out updated versions like flu shots. I think it's fairly plausible that this thing won't go away entirely, though, but rather become a more controllable episodic disease.

Well the other thing is that in the process of becoming endemic a virus typically needs to breed the lethality out of itself. A virus that causes isolation because of severe symptoms doesn't propagate well. The reason the flu is so successful in our biome is because it maintains a relatively low lethality. Yes we have more lethal strains going through the population every so often but in general it sticks around because on a relative scale of mild cold to ebola it's more of a nuisance rather than a danger. It's similar for a lot of our other endemic diseases.
posted by Your Childhood Pet Rock at 6:41 AM on May 2 [2 favorites]


mAbs can also be given subcutaneously and IM (there was one experiment dosing remdesivir this way on macaques but it didn't work nearly as well as IV) which means they can be easily self administered, potentially with autoinjectors. My predictions is that remdesivir is not going to work well in practice because antivirals have to be given early in the infection, at which point most covid patients will be at home. Self injecting IV drugs is not going to be a widespread solution, self injecting a mAb with an autoinjector is something hundreds of thousands of people do all the time (adalimumab among others comes this way).
posted by atrazine at 7:06 AM on May 2 [1 favorite]


Sure, it's promising! There's another study from China that did not show improvement though, and even this study did not show statistical significance in mortality difference between the placebo and drug arms.

So the study in question did show an improvement, but it was not statistically significant. That improvement was also found and was significant in a larger study very much means that the two studies don't disagree at all--the effect was small enough that the first study didn't have the statistical power to determine significance.
posted by thegears at 10:54 AM on May 2 [7 favorites]


One thing that's fascinating (to me) is to conceptualize the sheer scale involved. Hand-waving that the vaccine exists and that we're able to manufacture it in quantity, there's still the issue of how on Earth to distribute 7-billion (or so) of something. At a rate of 1 shot a second, that would take 221 years!--fragmede

The thing is, we did this once, with the swine flu shot in 1976. I remember getting a shot like that shown in the picture in the link--it was an injector gun type thing and it only took a few seconds per person. They vaccinated 1/4 of the US in short time, until they figured out that the flu wasn't as deadly as they thought and the shot was not as safe as they thought.

It is because of that second point that you want to make sure they take as long as necessary to make sure the vaccine is safe before they start giving it to everyone.
posted by eye of newt at 11:04 AM on May 2 [6 favorites]


Well the other thing is that in the process of becoming endemic a virus typically needs to breed the lethality out of itself.

There used to be widely distributed viruses far more lethal on a per-case basis than this though - smallpox being the obvious one. My understanding is that it's not just about viral evolution but viral evolution and human immunity and, uh society reaching a certain equilibrium? The global isolation response to COVID is sort of a unique situation because there's no existing herd immunity and when you isolate sick people it's too late, so there was a real possibility that it would rapidly sweep through the majority of the global population in a way that would completely saturate medical resources - or of course some places it did. If we end up at a point where a large number of people have had it, maybe there's a vaccine with the effectiveness of an average flu vaccine, it seems plausible that it will still sometimes pop up and be a problem for people but be a more manageable problem.

(Not pretending to be an expert on this so if my reasoning is incorrect let me know.)
posted by atoxyl at 1:59 PM on May 2


The global isolation response to COVID is sort of a unique situation

Sort of a unique situation in that this sort of spread was a possibility and we had some strategy for averting it, as opposed to historical cases of a dangerous virus being introduced to a population and then just killing a huge swath of people until that equilibrium was reached.
posted by atoxyl at 2:03 PM on May 2


Self injecting IV drugs is not going to be a widespread solution

Can't say I was expecting that particular skill to come in handy...
posted by atoxyl at 2:09 PM on May 2 [4 favorites]


remdesivir is not going to work well in practice because antivirals have to be given early in the infection, at which point most covid patients will be at home

There are some data that suggests it reduces severity of symptoms in those afflicted, even later during the infection phase.

It is a terribly difficult compound to synthesize in volume, however, and Gilead already seems to be voicing its patent rights over this drug very aggressively.

It would be straightforward for the government to go ahead and infringe those patents during a time of national emergency, though it is unlikely we would see the current industry-friendly regime do so, even if it meant saving lives.

A multifront search for other drugs is going to be helpful, esp. those approved with known safety profiles.
posted by They sucked his brains out! at 3:18 PM on May 2


Yeah, the sensible reaction to patent rights would be, "You know how eminent domain works during times of emergency, when the state has decided it really needs a piece of property for public purposes? Well, welcome to the intellectual property version. Here's a lump-sum payment we think is reasonable; this medication will be produced and distributed widely during the emergency. Later, you can have your monopoly back."

But it ain't gonna happen.
posted by ErisLordFreedom at 4:34 PM on May 2 [1 favorite]


There used to be widely distributed viruses far more lethal on a per-case basis than this though - smallpox being the obvious one. My understanding is that it's not just about viral evolution but viral evolution and human immunity and, uh society reaching a certain equilibrium?

But we did see it with smallpox. Variola minor. It displaced variola major in many endemic areas precisely because of its low lethality rates. Because patients didn't die and weren't so debilitated by the virus it was able to spread and started to cause far more milder infections.

Also, smallpox did keep dying out and reappearing as well. For smallpox to remain endemic required especially large populations where it could keep finding susceptible people to infect. Smaller areas had epidemics but the virus couldn't establish its endemicity. Japan for instance didn't have endemic smallpox up until very late in the game. As the disease did establish endemicity the death rates among the general population fell as the primary source of infections and deaths becomes children.

It was a scourge but one of the reasons the virus didn't have huge disruptions within endemic populations is because it didn't affect the breadwinners of the families who were largely immune. Children dying from it was a fact of life. Even during epidemic years within endemic areas the death rates struggled to top 1% of the population at large compared to an epidemic within a newly introduced population where a plurality or majority of the population could be killed off.
posted by Your Childhood Pet Rock at 8:02 PM on May 2 [4 favorites]


It is a terribly difficult compound to synthesize in volume, however, and Gilead already seems to be voicing its patent rights over this drug very aggressively.

The synthesis in the patent is like a laundry list of shit no person should ever want to use in a synthesis.

N-butyllithium (loves to decompose violently in water or in anything above sub-polar conditions)
Boron trichloride (Hydrolyzes to hydrochloric acid)
Trimethylsilyl trifluoromethanesulfonate (reacts violently with water and has a flash point a few degrees above room temperature, have fun with that one)
Trimethylsilyl cyanide (an organosilane that hydrolyzes to hydrogen cyanide, for when a regular organosilane isn't hazardous enough)

It reads like a senior chemist decided to try and kill the lab assistants by making them do reactions with all the most hazardous things they could think of.
posted by Your Childhood Pet Rock at 8:21 PM on May 2 [9 favorites]


It was a scourge but one of the reasons the virus didn't have huge disruptions within endemic populations is because it didn't affect the breadwinners of the families who were largely immune. Children dying from it was a fact of life. Even during epidemic years within endemic areas the death rates struggled to top 1% of the population at large compared to an epidemic within a newly introduced population where a plurality or majority of the population could be killed off.

This second paragraph is more or less what I was trying to say but I didn't realize that there was also an organic displacement of variola major by variola minor.
posted by atoxyl at 11:30 PM on May 2


There used to be widely distributed viruses far more lethal on a per-case basis than this though - smallpox being the obvious one. My understanding is that it's not just about viral evolution but viral evolution and human immunity and, uh society reaching a certain equilibrium?

Pathogens have critical community sizes below which they die out. This depends on a whole range of factors, like how well connected people are (the social graph), incubation period, transmission dynamics, etc. Some diseases have pretty high CCSs under historical circumstances and first emerged in humans only when human populations got large and inter-connected, this includes the wave of horrific diseases that afflicted the late Roman empire, and indeed that probably led to the collapse of the Eastern Roman empire as well.

This is also one theorised explanation for why we did not see novel Old World diseases hit the New World with contact by "Vikings". They were sailing on small ships, having coming from small communities in Greenland and Iceland which meant several serial intervals for most diseases had passed with small host populations. They then landed on the Canadian East coast, probably in communities not nearly as connected as the large urban societies of Central America or the dense trade networks of the Northeastern US.

RE: Remdesivir, if it turns out to work, it'll just be compulsorily licensed (or actually Gilead will license it to third party manufacturers to avoid the embarrassment). The real bottleneck is the synthesis which is a fucking nightmare. Every reagent is nasty, every step is low yield. That doesn't mean they don't get any royalties for it but if it really works then it'll be so widely used that a very low per dose royalty will be << cost of manufacture so I don't see that being an obstacle to availability.
posted by atrazine at 4:08 AM on May 3 [1 favorite]


N-butyllithium (loves to decompose violently in water or in anything above sub-polar conditions)

Doesn't it also burst into flames on contact with air, or am I thinking of something else?
posted by Mr. Bad Example at 5:58 AM on May 3


Doesn't it also burst into flames on contact with air, or am I thinking of something else?

You're probably thinking of tert-Butyllithium which is EXTREMELY pyrophoric .
posted by Your Childhood Pet Rock at 6:54 AM on May 3


There used to be widely distributed viruses far more lethal on a per-case basis than this though - smallpox being the obvious one. My understanding is that it's not just about viral evolution but viral evolution and human immunity and, uh society reaching a certain equilibrium?

But we did see it with smallpox. Variola minor. It displaced variola major in many endemic areas precisely because of its low lethality rates. Because patients didn't die and weren't so debilitated by the virus it was able to spread and started to cause far more milder infections.


It's about viral evolution as a function of transmissibility and population density. Basically, pathogens evolve within a certain kind of trade-off: not virulent enough fast enough, and your odds of being transmitted before a host clears the infection are minimized; too virulent too fast, and you kill the host before you can be transmitted to a new one. (Virulence = how fast the pathogen replicates and takes over the cells of the host.)

Now, where your sweet spot is, as a pathogen, depends on a couple of things. One is how dense your population of hosts is: if you have a lot of hosts, packed tightly together, you can get away with being REALLY virulent and ripping through them quickly, because the odds are that you'll encounter a new host to spread to before you've quite used the old one up. Another is how you spread: if you are spreading via a vector like a mosquito, for example, you can get away with being much nastier and sickening your host quite badly, because you don't need your host to be up and mobile while infectious to find a new host.

So viruses working with host populations that are very densely packed in big groups can afford to be much more virulent than viruses working with host populations that are sparsely scattered in small groups. By enforcing social distancing, we can actually artificially decrease our density and create incentives for the virus to evolve towards decreased virulence even if we can't test enough to completely eradicate and quarantine it. But evolving towards decrease virulence will not "just happen" over time no matter what we do--in fact, if it rips through cities or densely populated places without that distancing, it may indeed evolve towards higher virulence than it otherwise might.
posted by sciatrix at 8:08 AM on May 3 [7 favorites]


It would be straightforward for the government to go ahead and infringe those patents during a time of national emergency.

Wrong framing. There is no infringement. The award of a patent is a gift defined and granted by by congress. It is not an inherent right of the patent holder. Congress can change the rules regarding patents any time they like or eliminate them completely.
posted by JackFlash at 8:18 AM on May 3 [2 favorites]


While technically true the US via assorted trade agreements has been locking patents and copyright down for decades. Are they really unencumbered in that way? (I mean sure it's the Cheeto so they could just tell every other country to pound sand but that'll have a lot of fall out I imagine.

Remdesivir, if it turns out to work, it'll just be compulsorily licensed

Is there a mechanism in place for this already or would legislation have to be passed?
posted by Mitheral at 10:19 AM on May 3


Is there a mechanism in place for this already or would legislation have to be passed?

By my quick Google, in place for about 25 years, via the TRIPS agreement.
posted by rhizome at 1:38 PM on May 3


That is amazingly citizen friendly (if you have a non-corrupt government).
posted by Mitheral at 2:04 PM on May 3


Hostile states trying to steal coronavirus research, says UK agency.
Meanwhile, a dossier prepared by governments for the so-called Five Eyes nations, an intelligence alliance between Australia, Canada, New Zealand, the UK and the US, alleges that China deliberately suppressed or destroyed evidence of the coronavirus outbreak. Please note that the Australian Daily Telegraph is a Murdoch rag so this could well be part of Trump's China war.
posted by adamvasco at 2:35 PM on May 3


Chatter about China suppressing information is ramping up because the deplorables are trying to use it to shift focus of the Trump Administration's failures but of course the USA is suppressing information on their outbreak. Right Now.
posted by Mitheral at 4:41 PM on May 3 [2 favorites]




Holy shit that video is apropos and the graphics person that decided to make the Statue of Liberty's torch into a very Trump Hair-ian shaped flame.

*chef kiss*

Now if you'll pardon me while I go away to mourn for the hope of an intelligent sociological reaction.
posted by RolandOfEld at 9:24 AM on May 4


Wrong framing. There is no infringement. The award of a patent is a gift defined and granted by by congress. It is not an inherent right of the patent holder. Congress can change the rules regarding patents any time they like or eliminate them completely.

On behalf of those infected, soon to be infected, and those who may die, I hope you're right. I just don't see Congress acting to save lives, but on paper I hope you're right, for the sake of those who will otherwise die.
posted by They sucked his brains out! at 9:47 PM on May 4


Coronavirus is a very illustrative test of which governments value capital over constituents' lives.
posted by benzenedream at 10:35 PM on May 4 [2 favorites]




Wrong framing. There is no infringement. The award of a patent is a gift defined and granted by by congress. It is not an inherent right of the patent holder. Congress can change the rules regarding patents any time they like or eliminate them completely.

Which would lead to a 5th Amendment takings lawsuit for the value of the lost property right.

But it wouldn't come to that, anyway. There's already a simple mechanism for this: the federal government hires a contractor to make and distribute the drug, and the patentee either gives the government a license or sues the government in the Court of Federal Claims. The contractor itself is immune from suit and neither the contractor nor the government can be enjoined. The government is also immune from punitive damages. Since the end result is typically that the government pays a royalty, there's a strong incentive for the patentee to negotiate a license rather than sue.
posted by jedicus at 8:52 AM on May 7 [1 favorite]


Which would lead to a 5th Amendment takings lawsuit for the value of the lost property right.

You are assuming that they have an inherent property right other than what congress grants.
posted by JackFlash at 9:56 AM on May 7


A friend of mine works for Gilead. Looks like it helps a bit in recovery, that's it. But, reading the thread, and having had the thought a while ago that "holy shit, we are living through a major historical event!", has there ever been a pandemic before where we have realized what is happening, and have taken the measures we all have as it is happening? Was there mass social distancing during the Kansas Flu in 1918? Thinking back to Swine Flu, H1N1, SARS, MERS, etc, none went pandemic worldwide, and none saw this level of personal behavior changes that COVID has resulted in.

Maybe we are getting better? Hope it helps.
posted by Windopaene at 10:55 PM on May 7


You are assuming that they have an inherent property right other than what congress grants.

Getting to be a derail, but this is pretty well-trod legal territory. Patents are a property right ("patents shall have the attributes of personal property" 35 USC § 261), and in a line of cases stretching from 1882 to as recently as 2015 the Supreme Court has held that patents are a property right protected against government takings without compensation:
“[A patent] confers upon the patentee an exclusive property in the patented invention which cannot be appropriated or used by the government itself, without just compensation, any more than it can appropriate or use without compensation land which has been patented to a private purchaser.
Horne v. Department of Agriculture, 569 U.S. 513 (2013) (quoting James v. Campbell, 104 U.S. 356, 358 (1882)).

You can make a normative argument about this, but as a legal descriptive matter it is absolutely and unambiguously the case that in the US the government cannot use or revoke a patent without compensating the patent owner (except as provided for in the patent statute e.g. the government can certainly find a patent invalid for various reasons, but the government can't revoke a patent unilaterally just because it wants to use the invention for free).
posted by jedicus at 10:50 AM on May 8 [3 favorites]


Again, you are ignoring the fact that congress writes the law as to what constitutes a patent, what is patentable, how long the patent lasts, what rights attach to a patent.

I agree with you about existing law. But laws can be changed. What I object to is the notion that patents are an inherent right of patent holders. Patents rights are whatever congress says they are.
posted by JackFlash at 7:09 PM on May 8 [1 favorite]


Unless you're arguing for a constitutional amendment, no change Congress can make to the patent laws would allow Congress to revoke or appropriate an existing patent without liability under the 5th Amendment. Full stop.
posted by jedicus at 8:53 AM on May 9 [2 favorites]


Full stop! My, my. That's certainly definitive.

It's quite astonishing the deference some people give to patent and copyright holders, a corrupt system that is at the heart of much of the income inequality.
posted by JackFlash at 9:52 AM on May 9


no change Congress can make to the patent laws would allow Congress to revoke or appropriate an existing patent without liability under the 5th Amendment.

This is an opinion some people have, but it should not be confused with the law. Indeed, it has very little precedential support at all, as the Court of Federal Claims recently noted in Christy v. United States (currently on appeal): "The Supreme Court’s recent decision in Oil States does not disturb the principle that patents (including patent rights) are not property for Takings Clause purposes."
posted by Not A Thing at 9:59 AM on May 9 [1 favorite]


Just invoking the takings argument in a discussion sounds like Ammon Bundy. It's embarrassing.
posted by JackFlash at 10:10 AM on May 9


They sucked his brains out!: It would be straightforward for the government to go ahead and infringe those patents during a time of national emergency, though it is unlikely we would see the current industry-friendly regime do so, even if it meant saving lives.

There isn't a national emergency. If anything, there is an international emergency and there's more than one government involved. Some parts of this thread read as if this were just about the US...
posted by Too-Ticky at 2:48 PM on May 11 [1 favorite]


It would be straightforward for the government to go ahead and infringe those patents during a time of national emergency, though it is unlikely we would see the current industry-friendly regime do so, even if it meant saving lives.--
hey sucked his brains out!

Well that got me thinking. I remember reading about how a bunch of helicopter patents got purloined in the name of national defense during WWII (or was it Vietnam war? I read that article long ago). The implication was that companies tied to certain lawmakers could ignore the patents and end up dominating the industry while the patent holders went bankrupt.

Maybe a fair-minded pro-industry government might prevent the infringement of patents, but a corrupt government would be all for it if it benefited friends and family. Of course, that never happens nowdays.
posted by eye of newt at 9:39 PM on May 11


There isn't a national emergency. If anything, there is an international emergency and there's more than one government involved.

I'm not sure I disagree with you. Just noting that Gilead is very aggressive about ownership of this potential drug, and that the one country where related patents are held, which has the largest number of infected — internationally speaking — could do a lot to make that drug available to a lot of people, by ignoring or suspending those patents. *shrug*
posted by They sucked his brains out! at 12:08 PM on May 14


More than 140 world leaders and experts have called for future Covid-19 vaccines to be made available to everyone free of charge, amid growing tensions between drug companies and governments and a boycott of vaccine summits by the US.
The plea came as a French pharmaceutical company stirred outrage by saying any vaccine it discovered would be reserved for Americans in the first instance.
posted by adamvasco at 1:41 PM on May 14 [4 favorites]


Hannah Kuchler, Financial Times: Scientists vs politicians: The reality check for “warp speed” vaccine research
But many scientists feel a duty to damp the enthusiasm. They say a vaccine could take much longer because little is known about the disease and how bodies will react to attempts at immunization. In fact, some warn we may never create a vaccine for Covid-19.

Soumya Swaminathan, chief scientist for the World Health Organization, believes an optimistic scenario is a vaccine produced in the “tens of millions” next year, which would be mainly distributed to healthcare workers, and far larger volumes in 2022. To inoculate the world and defeat Covid-19 could take four to five years, she says.
posted by mbrubeck at 10:46 AM on May 25 [1 favorite]


But we "have to" find a vaccine "soon," there is "no way" we'll be sheltering in place for a long time. It "can't" go on forever, because it has gone on "long enough."

It's like a new school of thought: stupefactive governance.
posted by rhizome at 11:52 AM on May 25 [1 favorite]




US sanctions are hindering the distribution of Cuban drugs combating Covid-19
As biotechnology labs in Havana develop drugs to thwart the pandemic, the US blockade threatens further research and production.
"We joke in Cuba that if we discovered the remedy for the coronavirus, Donald Trump would choose to let all Americans die before buying it”, quipped Ernesto.
posted by adamvasco at 1:27 PM on May 29


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