CharonY

Well, that depends. When it comes to vaccines much of the donkey work is done anyway. E.g. safety of certain adjuvants or delivery methods is pretty well established, though it is still generally required to provide data that in combination they still remain safe (but requirements at that point are fairly low). Assuming it was effective to begin with, the question with mutations is why it renders it ineffective. And it is possible that new antigens need to be targeted then. And then one has to check whether the new target is actually effective.

Nah, folks don't panic, they just stock up on essentials, like toilet paper.. oh. But in all seriousness, the turnaround for vaccines is usually quite a bit faster as desired reaction is (i.e. showing immune responses) is fairly easy to measure (at least in principle). According to Pharm folks quite a few assume that the vaccine is not going to be used recurrently so there is a focus on cheap and easy. With the accelerated stream efficacy can also be tested faster which basically can allow a fast rollout of phase III. Essentially first a few hundred than a few thousand folks will be treated and tracked. There it will show whether there is a likely acquisition of immunity (i.e. in essence it is already a low roll out of vaccination and at least theoretically this could could happen this year). Say May/June first safety results, if all is well on accelerated Phase II say two months to ensure that titers are there and high enough to indicate immune response. While results roll in start recruiting and one might have the first rollout for III maybe as early as August (say a few hundred patients). If efficacy and safety is still alright at this step a next wave could roll out a few months later with a few thousand patients. While the vaccine is not available for the population as such, I am pretty sure some would claim at that point that success at this point already. However, in principle we would need more time to gather sufficient info from Phase III to evaluate how much protection the vaccine actually delivers. That could be tricky as at that time it is possible if not likely that the number of infections are already declining. Actual full production and rollout normally proceeds after it is known to offer at least some level of protection. One should also not neglect the psychological value of the development itself. It provides folks with a sense of potential control over the situation and even if it does not come out in time, at least it feels like someone is doing something. Oh, and I should add that the accelerate trials are (AFAIK) all sponsored by the respective governments, so it is not like the involved companies are hurting from doing it.

As usual, I am going to guess what you might mean. If the question is whether it is profitable if it gets developed but too late, the answer is how likely the disease is to become either endemic or perhaps seasonal. In these cases a working vaccination could be quite profitable. In a broader sense, many of these trials do not make money. This is part of the inefficiency of the pipeline and this is why most companies only commit after at least very promising pre-clinicals. In that respect these approaches are not very different from other biomedical pipelines. SARS vaccines were in development for a long time, but some shut down because there were no major outbreaks and money dried up, for example. Other than that, having more things in pipelines is generally a good thing, especially novel ones.

Actually there are several concurrent bets on the market, assuming that is what you meant.

As briefly discussed in dog another thread, this phase I is an abridged trial which is supposed to test safety. Data collection will take at least two month. After that they need another cohort to establish efficacy (and suitable concentrations) which takes even longer. As Kartazion said the projected overall time line is the often mentioned 12-18 months. In addition other trials are underway (many in China) for other vaccinations as well as treatment.

If they were freely and universally available and you make training available and you can make sure that folks understand risk and benefits then yes, they can be net beneficial. Thing is, I teach student labs which includes biosafety training. From what I have seen I have a hard time believing that sufficient folks would get it right. I mean I could be wrong and there may be net benefits but I do have my doubts.

That is why they allowed the phase I to proceed, there was a balance between need and risk. However, phase II is still needed. In this phase folks look into whether it actually has an effect. A harmless but useless vaccine can exposure folks to additional risk, as they think they are safe, while they are not. It is likely that Phase III can be cut short, essentially because there is nothing to compare it to. But again, the ~12-18 months time line is roughly what is needed to get the minimum information (and you also need to ramp up production) It does not really matter under which regulatory guideline you fall into. You always have to make sure that a) whatever you inject is not worse than the disease b) that it actually does something and c) figuring how and how much you need to apply to get and maintain the desired response. Just observing the responses even if you could inject everyone instantenously would take some time, otherwise you have no clue how you should deploy a potential vaccine. With regard to China I think I mentioned earlier that there are Chinese trials underway using a variety of approaches (inkl. using specific candidate antigens, most within Shenzhen). But as mentioned, I would be extremely surprised if someone somehow could bring anything to market by November (therapies would potentially be something, if only for severe cases). I should also add that having an immunogenic response does not mean that immunity has been acquired. On top there are international efforts in testing existing antiviral therapies some of which are intervention studies (i.e. they recruit sick folks as part of the cohort).

Ah but here is the rub. Dust masks only need to be fitted well and that is about it. However, a) for single use you discard them after the procedure requiring it and b) usually it is not a biohazard. Now if you wear them during your usual day, how likely is it that you do not fiddle with it, because you are not used to wearing them? How many fit the mask properly without someone checking? Also how certain are folks disposing them safely? And if they want to do that, through how many masks a day do they go? In hospital you have rather clear usage and dispose them after patient visits/treatment. Same under hazardous use. But casual use is likely result in re-use, and the moment you handle or put a potentially contaminated mask on, you increase infection risk. If it is not contaminated, it won't have helped in the first place... Procedures are not only putting on and taking off, it also includes safe usage while wearing them, disposal and renewal. For casual use the beavioural protocols are more difficult to establish and compliance is even harder. As such I doubt a net-benefit from common usage. One of the cases where it tilts towards benefit if folks are used to use them in a proper way and have sufficient supply to use fresh ones every time. Another is probably if one is an emitter in the first place (though of course the mask would become highly contaminated). However, for the general public just wearing them is likely to accomplish little to nothing. Also note that for common non sealed surgical masks various studies have shown that particles (representing aerosol droplets) can be recovered, which indicates that they have limited utility against airborne pathogens to begin with. The discussion whether surgical masks make sense for operations have been hotly debated for decades, for example. Some additional concerns are a false sense of safety, after all distancing is more effective than wearing masks in the first place and if wearing one creates a false sense of security, it increases risk again.

The capsid refers to the protein structure that encapsulates the nucleic acid (whether RNA or DNA). Some have additional lipids from their hosts. That latter part is what is considered the envelope.

Maybe one should consider them additive.

So pretty much in the same boat, we have starting to offer lectures via Zoom where you can share a whiteboard. It works well with a table attached, and other wise it is a bit awkward but workable.

It won't happen before November, and in this case in collaboration with the NIH, the pre-clinicals will run in parallel to phase I. Roughly speaking, the next steps tend to be more expensive (money and time wise) before a full roll-out can happen. Always assuming that these vaccines actually work. Also note that they are testing three different concentrations to ascertain safety and there is not guarantee that an of them will elicit an immune response (though they will also look at that as a secondary goal at day 57).

On a related note, Trump denied to be responsible for disbanding a task force that would deal with pandemics (similar to what other more sucessful countries have in place). Not sure what is worse at this point. Not knowing what they did out outright lying about it.

That is often a bit meaningless- after all it depends on how many folks are being tested and how widespread it already is and the latter is often an unknown. Symptoms alone are not sufficiently diagnostic. General recommendation is generally to self-isolate. Whether one should or even can get tested depends on how prepared the country is. In some enough test kits are around to test folks even with more than second degree contact. In others it is so limited that barely those in direct contact can be tested.

Just so you know, the phase I trial (which tests for safety) has a completion date in June. However, the follow up is supposed to take about a year.

That is a bit tricky. For coated viruses folks often see seasonality and it is suspected that at lower absolute humidity the viral particles stay infectious for longer (there are various hypotheses as to why, incl. osmotic pressure, staying longer in the air as aerosols etc., but no definitive answer AFAIK). While seasonality have been observed in various coronaviruses, there have been (as you noted) sustained transmission in humid regions. So folks by now assume an at best modest slowdown, but not a sharp decline.

Different markets in various countries have taken a range of measures, including limiting the number of folks allowed in, reserving hours for vulnerable persons, waiving delivery fees and so on. Not every country has a system for online pickup delivery and trying to implement it now is likely going to go badly. Some supermarkets in Germany are looking for help restocking since they cannot keep their shelves full.

I am not sure what you are seeing there, the first unbolded part is also true, as most folks are probably not handing them correctly thus providing no benefit (or in some cases increase risk) but those who could put them to good use then don't get them either. Edit: Do you mean the increase risk part? In my mind it makes sense - per standard biosafety procedure inproper use of face protection is a common risk (i.e. you should only use it when properly fitted, for the right application etc.). But do you mean that folks can misinterpret it somehow?

I read up in German articles in case of mistranslation and it does not look much better there. As usual nativism and cruelty go hand in hand (not to mention stupidity, as if nature adheres to borders).

Coronaviruses are RNA viruses. On the RNA strand they encode everything they need to replicate and form the capsids. I have mistyped earlier (ironically i did not proofread) and one of the genes it encodes a proof reading exoribonuclease. It excises mismatched nucleases. Other proteins required for basic processes such as ribosomes are hijacked from the host rather than being encoded in the viral genome.

I think it is too early to calculate mutation rates. However, coronavirus have something that is called a proof-reading polymerase. These reduce errors in while they replicate and thereby cut down errors (and hence, mutations). Right now we are pretty much past the point of containment. Even without draconian measures it can be possible to contain it, some countries managed to achieve that. However, what one need to do is quick testing and near perfect contact tracing. While Singapore, Taiwan and also South Korea did well on that end, many countries (incl USA and Europe) botched that, even with the time bought by China.

Iirc the Spanish flu put the immune system on overdrive, resulting in massive inflammation, which caused damages. Personally, I think with Covid-19 the issue is less about immune responses alone, but comorbidities. Preexisting conditions are highly correlated with worse outcomes and my guess is that those in conjunction with Covid-19 mediated lung damages are what is causing the fatalities. I.e.younger folks with those issues might also be vulnerable.

This is the basic idea for attenuated vaccines. However, ascertaining how is not trivial. That is unclear. If the dosage is too low it may not result in disease, but may also not trigger immune responses. Again, same idea for attenuated vaccines, but without studying what levels of inactivation and required dosages, it is rather risky (or useless). You can think in terms of inactivation. If you destroy their structure they become ineffective. As discussed before, cold is a not a specific disease and given the wide range of viruses causing such mild symptoms there was little incentive to develop a vaccine for each of these viruses. However, there have been work on SARS and from what I remember it was difficult but they were close. But funding effectively dried up as outbreaks were small and there was no sufficient economic incentives, I imagine. Any level of immunization as well as immune population reduces the transmission rate. Even if no perfect herd immunity is achieved it would make other measures (such as contact tracing) more effective.

So the paper discussing the use of cholorquine (and Remdesivir) is authored by Wang et al. (Cell Research volume 30, pages269–271 2020). The mechanism is not actually known but based on other viral data it is suspected to work by increasing the endosomal pH and interfering with glycosylation. The authors also speculate that modulating the immune system may also play a factor. Edit: apparently some studies with SARS suggest a role of zinc in inhibition, but from the looks of it most are in vitro data and I am not sure whether there are more studies out there.

Note that the spread was predominantly along trade routes. While there is decent evidence supporting the use of (black plague) bodies (which, btw. were already spreading in Asia and the Middle East), the entry of the plague was likely independent of that (or it may have contributed it, but was not the major driver). The narrative of the use of cadavers and the spread of the bubonic plague to Europe following the the siege of Caffa was strongly based on the account by Gabriele de' Mussi. Historians disagree whether he was actually physically present during the siege, but it appears that they think it is at least plausible that cadavers were hurled into the city. There is also the possibility that the plague arrived with the army and was subsequent transmitted by rodents, but despite overall uncertainties it is (from what I have read) not the favoured explanation. In the accounts de' Mussi also said that those escaped from Caffa were bound to Genoa Venice and so on and thereby spread the disease. However that clashes with what I think is now fairly well established understanding how the plague spread into Europe. It is well established that the plague spread over the Crimea, but cases in Genoa and Venice appeared well over 2 years after the siege of Caffa. Since even under unfavourable conditions the voyage should have not taken more than a few months, the timeline does not line up well. Another aspect that even if that timeline would have worked out, the time required would still have resulted in a substantial outbreak on the ships themselves. But again, around that time, there were no records of something that must have been considered to be a significant event. There are also folks who dispute that corpses were used in the first place (as there are no reports from folks fleeing from Caffa describing it aside from de' Mussi's account) or that there is no indication that it was knowingly used as a bioweapon (some dispute that bodies would be effective, they should have flung rats instead...). There is for example the speculation that the plague may have entered Caffa via the waterways. The Mongols were not able to fully block those and this where Caffa was getting resupplied. Also historians report that a step-wise entry of the plague into Europe is more likely which makes a spread over trade routes via Crimean ports even more likely. Well established reports pinpoint spring 1347 as the start of the plague in Constantinople, for example. I.e. there are quite a few reports that contradict the strong narrative of warfare-mediated spread, which is quite fascinating actually as not only historians have been working on it, but also epidemiologists and microbiologist, who use the documents to establish timelines and spread, not dissimilar to modern epi-studies (just with scarcer data). What is rather neat is that a fairly recent PNAS paper actually described genome evolution in Yersinia pestis which is consistent with repeated introduction via migratory and trading routes.