Machu Peach

Strict enforcement of "the line" greatly slowed things down in some areas and lead to a lot of waste (before those policies were relaxed). Israel and UAE, arguably the two countries with most successful vaccine rollouts, have been very flexible about who gets vaccinated in what order. The Israeli system has often been described as "organized chaos" and my friend (an MD) in UAE has said the process to get vaccinated was "show up with an ID and if we enough vaccine we'll vaccinate you." For all the concern, the US as a whole has had one of the more successful rollouts by many objective measures. It seems that Wisconsin has been/is a disaster, but I don't believe that's the case everywhere.

Certain states are doing well, others are doing poorly. From comments here it seems like Wisconsin is towards the low end.

For this disease and vaccine it's extremely likely have any vaccine that reduces disease severity will also reduce the number of infections, asymptomatic or otherwise. The Pfizer and Moderna trials were designed to look at disease severity because twice weekly PCR COVID screening of tens of thousands of people for 8+ months to detect asymptomatic infections isn't feasible.

This depends on what you mean by "treatments for viruses." Small molecule anti-virals remain difficult to invent and mass produce, but biologics like IFNa and IL2 (and even monoclonal antibodies) have show great success as therapies for specific diseases and their use is an area of great research.

That idea spontaneous vaccine-escape mutations would occur and spread without any sort of selective/evolutionary pressure seems extremely unlikely. Not completely impossible, but certainly quite implausible and I can't think of any examples of that occurring with any other disease. Once the vaccine is in widespread use (and if the vaccine does not offer sterilizing immunity) then you could potentially see escape mutations, but not now. Escape mutations are something that are always discussed. The COVID spike protein is quite large and has many epitopes (an epitope is what the immune system can 'see'). Generally the immune system will generate a strong immune response to one epitope and secondary responses to other epitopes. If the secondary responses are also able to control the infection than escape mutations become quite unlikely. (A 1 in 1,000,000 mutation is pretty much guaranteed to occur in an infection. Two 1 in 1,000,000 mutations, occurring simultaneously, is much much rarer. Three 1 in 1,000,000 mutations, occurring simultaneously, is near impossible. ...and so on.) The other thing to consider is escape mutations can (typically?) have major impacts on the fitness of the virus. Viruses have to outcompete their sister-virus in the same infection, so generally they quickly evolve to be very optimized and streamlined (compared with other diseases). Forcing them to make even a single, small genetic change will often severely hamper their ability to replicate and spread. So even if a vaccine resistant strain does evolve it likely will be less pathogenic than the wildtype virus.

I'm responding to this proposal. I can't speak for anyone else.

I don't have access to a lot of information specific to WI, so I would be grateful if someone could run the numbers without my estimates (and double check my math). If we pretend that 58k of vaccine was magically available pre-pandemic and it could either to go "teachers" or "people over 65" in Wisconsin... Option 1) If you randomly vaccinated 58k people over age 65 (assuming 90% vaccine efficacy) you'd expect to save roughly 340 lives. Option 2) If you randomly vaccinated 58k teachers (assuming 95% vaccine efficacy) you'd expect to save roughly 16 lives. It's not taking into account spread of disease, which is certainly an important variable. Teachers come into contact with more people (classrooms) than people over 65, but people over 65 come into contact with more vulnerable people (other people over 65 in social groups) than teachers, so that could go either way. This is about as simple of an analysis as one can do and I'm certain there are many other important variables, but it does highlight: 1) Having 58k people vaccinated before people over 65 will have a major, significant impact on mortality. 2) Protecting even a small fraction of people over 65 could save many lives. 3) If your goal is to save lives then to justify vaccinating anyone before the elderly they must either A) have an extreme risk increase (people with immunodeficiencies), B) be needed to care for COVID or the elderly (healthcare and nursing home workers), C) be at increased risk of spreading disease to people over 65 (healthcare and nursing home workers).

Gas station attendants (don't most people pay at the pump with a credit card?) -Remote work not possible. Indoor contact with many people, same as grocery workers who you put in the higher category. Construction workers (aren't most of them outside anyway, and how many are working on any one job?) - These assumptions are very very incorrect City workers (some, maybe, but not most) - Indoor contact with many people, same as teachers. Meat processors (lots of people in the factory, but not in a small enclosed room like teachers - they're spread out over a lot more square feet) - Remote work not possible, in person, indoors. Massive, massive COVID outbreaks in the spring and summer. Data show this is an extremely at risk group (for infection). "..but not in a small enclosed room like teachers" You've clearly never been to one of the plants. Truck drivers (how many people do they actually come in contact with?) - Remote work not possible. Vectors for long distance spread of new strains. Servers (indoor dining is banned where I live, and most places have limited capacity) - Remote work not possible. Teachers where I live have been insisting that they need to work remotely Clinical researchers(see: meat processors) - Remote work not possible, in-person interactions with at-risk groups constantly, generally in a hospital or clinical environment Warehouse workers (see: meat processors) Remote work not possible, indoors, with many many people (same as the meat processors that had massive massive outbreaks). To be clear, I AGREE that teachers are essential workers. I'm sure we can quibble about the risk ratio (both for death and for spread) in both a data-based or theoretical manner forever, but they're not fundamentally more at-risk than a host of other essential workers. In fact, serology data shows that they have the same or less risk than the average public service worker (for infection). I DO think it's extremely questionable to vaccinate any essential worker not directly involved in COVID or elder care (or care of specific vulnerable populations). I DON'T think that teachers are uniquely vulnerable (data agrees) or uniquely essential among essential workers.

Why would teachers get their own category? First responders, grocery store clerks, gas station attendants, construction workers, city workers, bus drivers, people who work in meat processing (or any sort of food prep), truck drivers, servers, clinical researchers, warehouse workers, etc... are all at the same level (or more) of risk. I don't understand this logic. It's like saying "Not all people born on May 8th 1990 (or whatever random characteristic) are healthy 28-year-olds. Many people born on May 8th 1990 have underlying health conditions that put them at an increased risk of serious infection. "Wisconsin has 700,000 people age 65 and older, and less than 300 people born on May 8th 1990. Vaccinating people born on May 8th 1990 isn't going to pose any significant delays in vaccinating people 65+."

Vaccinating anyone in any occupation not directly related to in-person COVID treatment or elder care (or the immunocompromised if they require care) before the elderly and immunocompromised is debatable. If everyone over 85 was vaccinated it would represent roughly 2% of the population. Roughly 32% of all COVID deaths have been people over 85. Over 75 would be roughly 7% and have been over 59% of all deaths. Over 65 would be roughly 16% and have been over 80% of all deaths.

This is simply not true. FDA meets in February to select the vaccine strains for the next fall. They're also based on surveillance data, often from strains circulating in the Southern Hemisphere's flu season, and are certainly not a "guess". As far as not getting the flu vaccine because one is not in a high risk category, it's the same logic people use when not complying with COVID mitigation efforts (and the same counterargument). One may not be in a risk category, but if infected one could spread it to someone who is.

The majority of current flu vaccine research is toward generating a universal flu vaccine, so I thought thats what you were referring. mRNA vaccine approaches could be part of that, but they would not address the main problems. As far as a shorter manufacturing time time leading to more accurate predictions of the seasonal flu strains, yes I suppose it could help. The current flu vaccine production strategies are archaic and better alternatives have existed for decades. Maybe this will finally generate enough motivation to update them.

It's easy to induce antibodies against either flu or HIV, but it's difficult to specifically induce protective antibodies. For flu you'll want to look into the concepts of "antigenic drift", "antigenic shift", and "original antigenic sin." Basically, flu strains can interact and trade surface components such that an effective antibody response against one strain can be completely ineffective against a new strain, even if they still bind. HIV has a massive glycan shield which protects it from most antibodies. This is further confounded by the fact that it's hard to get synthesized HIV proteins to fold exactly correctly. Additionally it has a famously low fidelity polymerase such that there can be multiple quasispecies within a single individual, leading to rapid immune escape mutations.

I am significantly more skeptical. Both flu and HIV have specific features that make them very difficult to vaccinate against. COVID does not have those type of features. mRNA vaccines have already been extensively tested against both flu and HIV and failed. I'm hopeful that eventually effective vaccines will be designed against both, but using mRNA doesn't solve the underlining problems with flu and HIV vaccine design.

For those interested in post-infection immunity. https://science.sciencemag.org/content/early/2021/01/06/science.abf4063

It's not that strange at all. There's no reason to assume you've had COVID if the tests were negative. It certainly possible that you had a low level infection that isn't detectable via the 3 rapid tests, but it isn't likely. The false negative rates of the rapid tests are only around 20%. I think many people overestimate the infectivity of COVID (and viral diseases in general). Think of how colds or the flu spread; sometimes everyone in a household is infected but sometimes only one person. Edit: I should add that I don't really trust the at-home rapid tests. I'm sure kits themselves are ok, but I'm skeptical that they'll be used appropriately by everyone.

Sorry if I'm misunderstanding, however I believe you are saying that there are concerns about side effects with older people and the immunocompromised. The data include a 65+ cohort segregated from the 18-65 population. The trends seen there are similar, but reduced. This makes sense as immunity generally wanes with age. Thus one would generally expect a vaccine to have reduced efficacy with the elderly, and also to have reduced side effects. The effects of vaccination on the immunocompromised would depend greatly on the exact nature of their immunodeficiency so it's hard to draw conclusions. I suspect that most people with severe immunodeficiencies would not be eligible for the vaccine.

I agree completely. It maybe says something about the testing protocols in place, but even with that it's flawed. From my point of view it's a largely useless statistic.

Systemic adverse reactions fall into 'solicited' and 'unsolicited' categories. With solicited adverse reactions the investigators ask questions like "Did you have a headache?" and so on. With unsolicited they ask "Do you have any other symptoms?" I think it would surprise no one to learn that people are far far more likely to report solicited adverse reactions than unsolicited. In the Moderna trial linked in the Vox website 57% of people reported a solicited adverse reaction after receiving the first vaccine. That may seem crazy high until one sees that over 44% of the placebo group also reported a solicited adverse reaction. ...think about that for a moment. With these criteria almost half the people who got a single injection of saline (or similar inert formulation) reported a systemic adverse reaction. "Severe" reactions (also called grade 3) refer to anything prevents your normal daily activity (and above). So if you take a painkiller for a headache or injection site tenderness or if you feel fatigued and skip a workout or take a nap you've had a "severe" reaction to the vaccine. In this study 17.4% of people reported "severe" reactions after the 2nd injection with the vaccine group and 2.1% for the control. These are almost completely of the headache, fatigue, muscle pain, and joint pain variety. (As an aside, these are all 'symptoms' of a strong immune response and as a result I am a lot more optimistic about the duration of immunity than I was before seeing these data). There is no difference in grade 4 reactions (things that require an ER visit or hospitalization) between vaccine and control groups.

As far as I am aware the first and second dose are an identical product. Any sort of longer term boost would very likely be just a 3rd dose of the exact same vaccine (though getting the FDA to agree to using it like this would require an additional or modified EUA). There's no immunological reason to think you'd have to prime/boost again.

Both the Pfizer vaccine and the Moderna vaccine are two doses. The vaccines are extremely similar in most respects. They do differ in the type of delivery system, though that is also conceptually similar. That difference allows the Moderna vaccine to be more stable at standard freezer temperatures. There's also a slightly different in schedule with the two doses of the Pfizer vaccine given 21 days apart and the two doses of the Moderna vaccine given 28 days apart. I suspect that this is due to a difference in protocols during testing and that the timing difference is mostly nonconsequential. Patients pretty much get a choice to refuse whatever treatment they receive, so I'm sure you'll have to right to refuse (though it might be required by other organizations). I suspect the receiving the alternative vaccine would depend on availability, so getting it in a reasonable timeline might not be possible. I would bet that over 99% of primary care physicians would not be able to tell you the mechanistic differences between the two vaccines and would have no reason to recommend one over the other at this time. Edit: Found another difference. Pfizer's vaccine is authorized for those 16 and up and it looks like Moderna's vaccine will be for those 18 and up. ...again, I think this is a result of trial design (who was enrolled in the trials) and not any mechanistic difference.

For what it's worth, we were taught one meter for respiratory diseases in grad school (of course it's all probability). I've never figured out how that got adjusted to 6 feet for COVID.

I see. It looks like most of the studies pertaining to the spring semester were published a couple months after that semester ended. I imagine that collecting and analyzing student achievement data in realtime is very difficult. Maybe we'll start to see more quantitative studies about the fall semester in Jan/Feb 2021?

Is there any legitimate evidence of this at this point beyond personal assumptions and anecdotal experiences/opinions? Here's a statement from AAP in August. I'm not sure one could consider it legitimate evidence, but it an informed opinion from a relevant professional organization. They don't describe e-learning as a 'trainwreck', but do highlight negative consequences. https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/covid-19-planning-considerations-return-to-in-person-education-in-schools/ Edit: This is first time I've bothered looking into in personal vs remote learning as it seems highly emotionally (sometimes politically) charged and I don't really have a dog in the fight. However it seems well documented that e-learning exacerbates the achievement gap experienced by minority students. That's not really an issue for a lot of places in WI, but it is for a large fraction of the country.