Tuesday, August 24, 2021

The Ethics of "Off-Label" Vaccinations for Kids

The WSJ reports that some parents hope to get their kids (under 12) vaccinated against Covid, as "the FDA’s approval generally means vaccines are eligible for off-label use, meaning beyond approved populations."  However, "the FDA and Centers for Disease Control and Prevention have emphasized that the safest thing for this group of children is to wait for more data to be analyzed."

I'm curious whether it's really true that waiting is "safest", or whether these advisories ignore status quo risk. I don't have the empirical knowledge to answer what really would be safest here, but questions worth asking include:

(1) How many kids in this age group are expected to (i) suffer serious ill-effects, or (ii) die from Covid during this "wait"?

(2) Given our background knowledge of similar vaccines, including the results of clinical trials for this vaccine on adolescents, what proportion of kids would you expect to (i) suffer serious ill-effects, or (ii) die if administered a "best guess" fractional dose of this vaccine?

It would be pretty extraordinary if the vaccine posed a greater risk of death than Covid.  But if it doesn't, that would surely go some way towards undermining the assumption that waiting is necessarily "safer": it increases your child's risk of death!  Perhaps the risk of non-lethal but still serious vaccine side-effects could be great enough to outweigh the (typically mild) risks from Covid for this age group?  Maybe... The comparative risk is something I'd really want to hear explicitly addressed by medical experts before trusting the FDA/CDC advice, given how ethically incompetent these agencies are.

Put another way: it could be worth asking your pediatrician: "Given all that we currently do and don't know about the possible risks of each, would it likely be overall safer for my kid to get the Covid vaccine off-label or to get infected with the Delta variant while unvaccinated and waiting for more data?"

I would be amazed if they suggested the latter.  Granted, that doesn't settle the matter because infection during this time frame isn't certain.  But the rates are very high in a lot of places.  So discount in proportion to whatever probability you assign to your kid's risk of infection.  E.g., if 25%, you could ask: "Would it be overall riskier for four kids to get vaccinated off-label or for one to get infected with Delta while unvaxxed?"

I'd be willing to bet that the FDA/CDC do not in fact have any data to suggest that the latter is safer, and that their announcement instead reflects a failure to account for status quo risk.  Especially once you take into account the positive externalities of vaccination (e.g. if there are high-risk / immunocompromised family members to be protected) I suspect that many families actually ought to pursue off-label vaccination (at reduced dosage) contrary to the FDA/CDC advice.  But that's merely a guess. (Ask your doctor!)  It would be really nice to have medical experts or the public health community address the relevant comparative questions, so that we could have a better idea of what the actually safest option is for families at this time.

A final point.  Consider the following passage (from the WSJ article):

Parents have been clamoring for months to vaccinate their children under 12, says Scott Krugman, a pediatrician at Sinai Hospital in Baltimore. He says that while parents might point to other drugs that are routinely used off-label for children, such as acid blockers or asthma medicines, pediatricians “have never really used vaccines in an off-label way.”

A vaccine is different from medicine used to treat an existing illness or condition, he said.

“If you are giving something to someone who is perfectly healthy, the burden is on making sure there is no potential side effect,” he says.

This is very much the wrong way to think about the question. In the midst of a raging pandemic, nobody unvaccinated is "perfectly healthy".  They are vulnerable to infection.  If you place a "burden" on "making sure there is no potential side effect" to vaccines then you are going to leave more people vulnerable, with predictably worse health outcomes as a result.

Remaining unvaccinated risks very serious side-effects.  So there should be no special "burden" weighing against vaccination.  The only question is whether the side-effects of vaccination are worse (in expectation) than the side-effects of non-vaccination.  Anyone who isn't answering this question simply isn't telling you what you need to know in order to determine the safest course of action.


  1. I think you'd win that bet about the CDC, given that the CDC does not appear to assess vaccine risk matters properly, based on what I've seen so far.
    In terms of what is the safest option for children, I'm no expert in vaccines, but I think 'safest' has to be 'safest based on the available information'*, so I reckon vaccination is the safest option, at least on the basis of the information I have - which is general information about vaccines and covid, not specific about vaccination of children. For many parents, vaccination for their kids is probably also the safest option.

    *For example, sometimes a person dies due to a vaccine, but wouldn't have died or suffered a worse consequence due to the illness the vaccine was meant to prevent. In that case, full information (i.e., knowing all there is to know about how the universe work and about that person at that time) at the time of vaccination almost certainly would have been enough to predict death as a result of the vaccine, and probably also nothing worse as a result of the illness. Or at least, it would have been enough to say the former was much more probable. But that doesn't mean they didn't go with the safest option by taking the vaccine, as 'safest' doesn't mean 'safest by full info'.

  2. For additional support, note that the official FDA/CDC line implies that participants in the current clinical trials are sacrificing their own safety, but I doubt that many actually believe that of this case.

    Put another way: should parents of the current clinical trial participants really hope that their kid is merely getting placebo? You'd have to think so if you buy the FDA/CDC line. If you instead think it makes sense for these parents to hope that their kid is getting the real vaccine (and believe that this is the safer option), then it must also make sense for many other parents to likewise believe that it would be overall safer for their kids to get vaccinated at this time.

  3. Hello Prof Chappell.
    I would like to add something to the following statement of yours:
    “it could be worth asking your pediatrician: "Given all that we currently do and don't know about the possible risks of each, would it likely be overall safer for my kid to get the Covid vaccine off-label or to get infected with the Delta variant while unvaccinated and waiting for more data?" I would be amazed if they suggested the latter. “

    A dimension in the expected values calculation that may be making a difference is the following: leaving aside for the moment the risks that the Delta may be posing for children, natural infection may be conferring a long term benefit that the current vaccines maybe cannot. I am quoting a distinguished Israeli Professor of immunology, Cyrille Cohen of Bar Ilan University in Israel. It should be noted that the date of the interview is July 17, so the information may already be dated, but it serves the broader point I want to make. I quote him:


    “We need more solid data regarding the efficacy of a third shot for healthy and low-risk people. We need to draw our conclusions from data, and not jump to conclusions just because Pfizer has put out a press release.
    “We’re not injecting orange juice; this is a vaccine and we need to know whether it will really boost immunity and whether it’s needed.

    [T]he companies are working on it [to adjust the vaccines to give extra protection against new variants], working on making a comprehensive vaccine. It’s possible that boosters will be adjusted to cover a broader part of the spike protein than current shots.

    “We will not vaccinate kids without the results of clinical trials, which are currently underway with 4,600 children. But even then, you have to make a risk-benefit calculation, which is very different with kids, who don’t tend to get seriously sick within COVID-19, than with teens and adults. Mortality for kids has been very low and you don’t want to take risks with vaccines if the disease poses very little risk.
    “We don’t have enough understanding on these vaccines for kids and to base our decisions only on a 4,600-child trial, especially as half of these will receive a placebo.”

    ““I’m not overly concerned about the contagion among kids per se. But we have to take into account that they could infect their surroundings and people at risk. ... And while I am certainly not saying that anyone should expose their kids on purpose to the virus, there may be a positive side to infection of kids by a variant that isn’t causing them harm. Because in a sense this boosts their immunity against possible future variants that could be worse.“For adults also, while I stress again that no one should get infected on purpose, if people are vaccinated and catch a variant that doesn’t harm them, it can serve as something akin to a third dose, helping to protect against future variants that could be worse.

  4. PART 2
    Now, he is not explicitly making the point that the positive side effect of an unplanned natural infection to which he referred, namely the side effect of acquiring protection against a future variant that is more dangerous, could be the sort of protection that couldn’t have been gotten by a vaccine, but it is a common talking point that I have encountered among epidemiologists and immunologists(for a different view see (1) ), namely that natural infection typically confers “broader” immunity but at prohibitively high risk – in other words, it may typically protect more than vaccination against future variants or even novel similar pathogens, but it should be avoided because it is far more risky than vaccination. As an example, I quote a leading infectious disease epidemiologist, Oxford Professor Sunetra Gupta, along with Stanford Professor Jay Bhattacharya and Harvard Prof Martin Kulldorff :


    “Natural infection typically confers better and broader protection, but this comes at a cost to those who are vulnerable to severe illness and death. For those in the vulnerable group, including the elderly and those with chronic disease, it is safer to acquire future protection against the disease via vaccination than by recovering from the disease.

    The point of the Israeli Professor about the possible innocuousness of natural infection for children is explicitly made by an independent expert advisory committee that advises the United Kingdom health departments on immunisation, Professor Robert Dingwall (the date is June 30, 2021, the info may be dated):


    “Allowing children to catch Covid-19 naturally may be better for them than vaccination, according to a member of the committee deciding whether to offer jabs to teenagers.
    Professor Robert Dingwall, of the Joint Committee on Vaccination and Immunisation, said that given how mild illness was in teenagers, vaccines had to be “exceptionally safe” not to do more harm than good.

    “Although Dingwall is a sociologist, his views have significant support among epidemiologists, who suggest natural infection among young people would be a good way of “topping up” immunity in the population in the long term”.

    “Teenagers are at intrinsically low risk from Covid. Vaccines must be exceptionally safe to beat this,” he wrote on Twitter. “Given the low risk of Covid for most teenagers, it is not immoral to think that they may be better protected by natural immunity generated through infection than by asking them to take the possible risk of a vaccine.”

    1. PART 3
      It should be noted that his point rests only on the possible downsides of vaccination for children given their very low risk from Covid, he is not making any claim about the positive side effect of natural infection that the Israeli Professor made.
      But there is also a possibility, if I understand correctly what I read, that natural infection from Covid is indeed preferable for children, given their very low risk (1 in a million, according to Prof John Ioannidis(2), similar with the initial estimates of the CDC, 1 in 500 thousand according to Prof Bhattacharya, if I remember correctly his statement—sorry, no link for Prof Bhattacharya--), not on account of the “broadness” of the immunity that natural infection confers, but due to the different route of infection that natural infection offers, compared to the present vaccines. I am referring here to what I have seen referred to as “mucosal immunity”, and I am quoting a science journalist that I had seen being retweeted by philosopher Mark Alfano on another Covid subject in the past, so I take it he is a credible science journalist (this link is recent, August 10, 2021):


      “And vaccines do not offer 100 per cent protection against catching it [Covid].

      Why is this? Because the vaccine is given in the arm, but the antibodies are needed in the nose.
      “It will stop a systemic infection. But it’s hard to keep those antibodies up in the nose,” says Nobel laureate immunologist Professor Peter Doherty. “And you can’t keep high antibody levels in the nose with a vaccine you give in the arm.”
      A word on this, before you worry too much: this data is just for catching the virus. The evidence we have suggests both Pfizer and AstraZeneca do a great job of protecting us from dying from the virus, which is what really matters.”

    2. PART 4

      So if the immune system is taught by natural infection it may learn to develop antibodies in the nose, because the route of entry of the virus in the body in natural infection is through the nose or mouth. If that’s the case, doesn’t this count as a benefit in case a future very dangerous variant shows up?(the question is not rhetorical, I am really asking, but I speculate the answer is yes).

      Here is another reference to mucosal immunity by scientists, which also makes a tacit reference to the fact that being infected by the natural virus, leaving aside the greater risk that it poses compared to vaccination, confers the positive benefit of teaching the immune system in a very appropriate way. The link was in a study I saw retweeted by former Yale University’s Preventive Medicine expert Dr David Katz, who I hasten to say supports (non-mandated) child vaccination (3):


      Factors such as age, genetics, and comorbidities appear to reduce the effectiveness of vaccines, including those against influenza, in certain individuals, Memoli said. “What I think is the problem is that every person is unique, and their immune system is unique.”
      The solution, Memoli said, is to stimulate multiple aspects of the immune system, which could be done using inactivated whole virus or multiple antigens from a variety of viruses or combining different vaccine strategies. He and Taubenberger have decided to pursue the killed whole virus approach, using a cocktail of several killed whole coronaviruses.
      They’d like to be able to deliver a pancoronavirus vaccine via a nasal spray. “All of these viruses, they get in through your mucosal system,” Memoli said. “The big problem is we don’t understand enough about mucosal immunity for respiratory viruses. This is a big unexplored area.”
      Rather than killed whole viruses, biopharmaceutical company VBI Vaccines uses synthetic virus-like particles (VLPs) in its candidate pancoronavirus vaccine.

      “Conceptually, we know that VLPs are very effective vaccines,” VBI Vaccines Chief Scientific Officer David Anderson, PhD, said in an interview. “They’re just really great ways to educate the immune system, because they look so much like the virus.

      More on mucosal immunity and on the value of vaccine design mimicking the process of natural infection so as to take into account the route of entry of the virus (which means that natural infection does indeed teach wisely, albeit dangerously, otherwise there wouldn’t be such attempts to make vaccines imitate in detail the way that natural infection teaches) at the Atlantic (4).

    3. PART 5

      A final point to be taken into account: the death rate from the Astra Zeneka, according to a study in Norway that Prof Ioannidis had cited in April 2021 as a very credible country in pharmacovigilance (5), was one in 43 thousand – an ultralow risk. Now, the deaths were concentrated among people between(approximately) 30 and 50 years old, and I would like to ask if anyone thinks that this is important. I mean, if the particular vaccine or other vaccines, unlike Covid, is not tracking degraded immune systems when it kills, then how optimistic should we be that the data about the safety from the vaccine trials in children that we await will improve dramatically upon the Norway death rate number for adults? Let us remember that we are trying to beat the one-in—million death rate of Covid for children (or at least healthy children) or the one-in-500 thousand (I am using either Prof Ioannidis’s or Prof Bhattacharya’s estimates). How likely is it that a vaccine will do better than the 1 in 500 thousand death rate for children, given that it was killing 1 in 43 thousand while concentrating the death on relatively young adults(30-50) ? If the vaccine was harming in the same way with Covid (i.e. less and less as we move lower on the age ladder) we could be optimistic. But with the deaths from the vaccine accumulated among 30-50 years old, according to the study cited by Prof Ioannidis, I wouldn’t be. But I have no clue about the science, these are questions I would address to people with knowledge of Medicine. I would be interested though to know if you find my rationale plausible.
      To conclude, Prof Chappell, do you think we should take into account the possibility that natural infection in healthy children may be arming them better than vaccination against future dangerous variants? Whatever your answer, I agree with you that the vaccine should be available to both teenagers who want it and to parents who want it for their young child. The issues seem to me quite distinct, I would never use any vaccine on my child for this level of threat that children now face from Covid, but I also think it is impardonable that the vaccine is not made available for parents who crave it for their child or for teenagers who crave it for themselves. I think it’s safer to not vaccinate children, but I also think that the right to decide about one’s own health trumps safety. We cannot arrange our society in a way that people will feel aggrieved towards the State on issues so fundamental as their bodily well-being. This is a recipe for making people bitter or even hostile.

    4. PART 6

      1: I quote Dr Gideon Meyerowitz-Katz, aka Health Nerd, Epidemiologist at University of Wollongong:


      “Vaccines give us immunity against diseases, often to a greater extent than contracting the disease itself, and without the nasty consequences of being sick.”

      From what I have seen on the internet, his position regarding “the extent” of immunity is atypical among epidemiologists and infectious disease scientists that I see quoted on the internet (as opposed to Dr Meyerowitz’s view about the lower risk of vaccination vs natural infection which is unanimously accepted), but I have no clue what’s the established scientific view (or sentiment) on the issue of the extent/broadness of the immunity. I had asked here, at Prof Chappell’s blog, a variant (no pun intended 😊) of the same question in case anyone knew the dominant view, but I I got no answer (March 22, 2021):


      ““But in case someone is interested let me motivate a future discussion with a question of scientific fact that I have been unable to find a definite answer for: Is the immunity from natural infection always better, always worse, or sometimes better and sometimes worse from the immunity that is developed from vaccines? The answer to this question of scientific fact is philosophically relevant for deciding on issues of rationality about certain people’s refusal of vaccinations: is there a way of knowing now for sure which from the two possible immunities (immunity from natural infection, immunity from vaccines) is better? I am asking here that we leave aside temporarily the different level of risk involved in getting each type of immunity (the natural infection on average represents far greater risk compared to vaccine-acquired immunity) and concentrate only on the question which of the two immunities is more protective against future reinfections, and/or against future mutations, and/or against future novel pathogens. In the last case, the case of protection from future novel pathogens, I am assuming that it could be in principle possible that the immunity that one develops now to Covid can act as cross immunity against a future different pathogen. I have no clue if this is even possible, I extrapolate from what I have read about immunity to previous viruses acting as a shield against other viruses (cross immunity). If someone happens to have a link, any answer is welcome, the comment sections of analytic philosophy blogs are the most epistemically responsible comment sections I have ever come across. My own impression is that there is no definite answer as of the time we are speaking, judging from conflicting statements from Professors of Medicine that I have encountered.”

    5. PART 7

      2: Prof Ioannidis, min 5:05, says the chance of death for children is around 1 in a million (the statement made on May 11, 2021). He is saying it is not wrong to vaccinate children (but he is against mandating it) but he does not consider it a priority (the video is in Greek, he is on the News):

      The CDC in July 2020 was citing the same figure:


      A few days ago (Aug 24, 2021) Prof Ioannidis repeated his claim (again in Greek) that children have “exceptionally low risk [“danger”, “κίνδυνος»”] of dying from Covid (but did not repeat the 1 in a million claim), he said the decision to vaccinate one’s child should not be feared but should be voluntary.


      3: Dr David Katz, August 4, 2021, min 6:00


      4: From the Atlantic,, on the benefits of mimicking Nature re the route of infection:


      “Another company, California-based ImmunityBio, plans to push the pro-T-cell paradigm even further. It has several versions of a spike-nucleocapsid combo vaccine in clinical trials, some of which are being delivered as drops into the mouth, and will soon be testing out an intranasal spray. Patrick Soon-Shiong, the company’s CEO, told me that this route of administration is a much better pantomime of how the coronavirus actually enters the human body—through the airway, where it will encourage the production of unique populations of antibodies and T cells tailor-made to guard these tissues. Many of those T cells will even hunker down in and around the lungs, where they can head off the virus immediately, something that doesn’t happen as efficiently when we inject vaccines into our deltoids. “I think local immunity is going to be what we need, if we’re thinking ahead,” Donna Farber, an immunologist at Columbia University, told me. Some next-generation vaccines could operate as solo acts for the un-immunized; others could be boosters for people whose defenses against the coronavirus are no longer up to snuff.”

      5: Prof Ioannidis on April 20, 2021 (4 months ago, the info may be dated), min 12:00, praising the pharmacovigilance of Norway and stating the 1 in 43 thousand death rate for the vaccine as credible (and 1 in 26,000 the risk of serious side effects)


    6. Hmm, given how much people were freaking out over a 1 in a million chance of blood clots, I don't believe that any fully FDA-approved vaccine would have anything remotely like a "1 in 43 thousand death rate".

      I gather that the Delta variant is somewhat worse than flu for youngsters (in terms of hospitalization risk), and I think it's well worth getting kids vaccinated against the flu.

      But in principle, sure, it's conceivable that one could make an argument for natural infection based on possible greater protection from worse future variants. In practice I think such a case would be weak because (1) The empirics seem very murky -- early on there were lots of articles talking about how vaccines can provide stronger immunity than natural infection does; (2) I don't think we need to worry much about future variants because now that the infrastructure is in place, they'll be able to pump out a refined mRNA booster vaccine very swiftly; (3) having said that, natural infections are how variants arise and spread, so more widespread vaccination seems helpful to further reduce the population-wide risks here.


    7. I'm not sure about the 1 in a million number. I haven't seen good data, but at least what I've seen are much higher, most of them from 1 in 50000 to 1 in 100000 roughly for blood clots (higher numbers for younger people, though it's unknown for children). The fatality rate has been estimated at 23% (e.g, https://www.theguardian.com/world/2021/aug/11/oxfordastrazeneca-vaccine-rare-blood-clot-syndrome-has-high-mortality-rate ), but that number has been disputed and it's hard to find good information. Here it's 50% without proper treatement, but 19% with it ( https://www.bbc.com/news/health-57260463 ).

      Other studies give different numbers, so it is hard to tell. So, it's hard to tell. Since it seems to be worse for younger people (at least among adults), going by 1 in 50000 and 1/5 fatality rate, that's roughly 1 in 250000 fatalities from blood clots, and it's improbable that the vaccine will many people in other ways.

      On the other hand, the number of COVID fatalities of children in the US seem to be so far: ( https://data.cdc.gov/NCHS/Provisional-COVID-19-Deaths-Focus-on-Ages-0-18-Yea/nr4s-juj3 ).

      0-4 years old: 148

      5-18 y0: 338.

      The population is:


      0-4 years old: 19694371
      5-18 years old: 53503043

      So, Covid Fatalities:

      0-4 yo: 133070
      5-18 yo: 1 in 158293

      Given no further information, AZ would seem to be a better choice than non-vaccination, given also the protection it would give to other people (though in reality AZ is not used in the US, and there is no data of similar risks for Moderna or Pfizer-BioNTech).

    8. Hi Angra. I think it's important to find out how many of the dead children had comorbidities (i don't know if there is any evidence on this). The majority of the children are healthy, so if the deaths are mostly children with comorbidities then the death rate for the healthy ones will be far lower. The JVCI states it is motivated by precisely this consideration (i.e. the risk healthy children):


    9. A missing word in my last sentence: "i.e. the risk to healthy children".

    10. Hi dionissis,

      in re: comorbidities, granted, I do not have those numbers. On the other hand, I considered the fatality rate not among those who got infected, but among the general population. The fatality rate among those infected would likely be far higher, though it's also not known how high. So, information is sketchy, but going by that limited information, it looks like a better option than no vaccine.

      At any rate, the AZ vaccine was not approved in the US, and it's perhaps the worst of the usual vaccines (if not of all) in terms of serious side effects. Take for example the J&J vaccine, which was approved by the FDA and uses a viral vector technology, like the AZ vaccine. Once again information is sketchy, but going by what I've found, seems that the blood clots happen in far fewer cases than with AZ, and they are also much less lethal (e.g. see "Selected Adverse Events Reported after COVID-19 Vaccination" on the CDC website; also d41586-021-02291-2 for some possible causes for the differences ).

      So, even granting for the sake of the argument that vaccinating kids with AZ would not be good, J&J does much better with the same sort of technology.

      In re: the video you linked to, I watched it, but the doctor is talking about effects of mRNA vaccine. The conditions he's talking about do not have a link to viral vector vaccines.

    11. Also, regarding the video, he says "there is a risk that we could be doing more harm than good with this vaccine, and in that situation, even though it's not very likely, we really are cautious to advise that all children should receive the vaccine". But if "it's not very likely" is less than 50% of more harm than good (it sounds like it), and there is more than 50% chance of more good than harm, then yes, he should recommend it (unless he thinks there is a good chance of just as much good as harm, which seems improbable).

      Also, when assessing potential harms, he is only talking about health risks from the vaccine vs. covid for the kids. But harms to children does not come from that only. For example, surely losing one or both parents would cause great harm to nearly any child. Children generally live with their parents. And can give covid to their parents. Vaccines would likely reduce the risks of that. And the risk to their grandparents and other closely related adults, even leaving aside the risks for the general population.

      That aside, the numbers do not seem to support his case, so see -COVID-Shimabukuro-508 : for females, there is no increase of those conditions over what was expected following first dose, and some increase but extremely rare for males, some extremely rare for females after second dose, and much higher for males but still low given the fact that the conditions are usually not lethal.

      Aside, there is an internal problem for the arguments he's giving: the increase in those conditions is many times higher for males than females, but he's not making a distinction. Yet, with those differences, if 'caution' were appropriate for males, 'go ahead, get the vaccine right away' would be the clear choice for females, whereas if 'caution' were appropriate for females, 'just don't get it at all' would be the clear choice for males (always except for cases with some unusual characteristic).

    12. (well, the problem is internal assuming he looked at the data and is taking it into consideration when making the assessment)

    13. Hi again Angra. The only reason i linked to the video of the JVCI i posted was to make salient the consideration that there is indeed a different IFR for healthy children. I was not trying to make any point about any specific vaccine, and i have no opinion as to what the health authorities in the UK or the US should recommend, if anything because pharmacological medical interventions are so out of my mind that i cannot properly relate to the well being concerns of those who do get regularly vaccinated. My major concern is the mandates, a fortiori the unnecessary mandates that are targeting indiscriminately people (or families) like me who are offering to be deliberately infected. Lots of people in Greece that i am talking to are in this category (i.e. feeling ok with deliberate infection so as to gain the Green Pass), as i have found out the last couple of months. Hence my trying to draw attention to the fact that healthy people at least who are offering to be infected in lieu of vaccinated have a reasonable objection to mandates. Here is a CDC link, a big study, showing almost 95% of those hospitalized had one underlying medical condition, and from those who died it was 98.5% that had an underlying condition:


      My educated prediction is that it won't be too long before the Covid vaccines will be mandated, let alone be recommended, for children too.


    14. Hi again dionissis,

      I see. Okay, so in that case, I don't know whether the logistics for deliberate infection are available (and at a reasonable cost for the government, given alternative uses of the resources), without endangering the rest of the population. If they are, and infection provides at least a reasonable amount of immunity (i.e., not significantly less than two doses of a vaccine), then you might have a case against the government, though there is the question of risks to children, and indeed given no further info, it's a priori very probable than a vaccine will be much better than a disease (if you're not convinced, you can go with dead virus vaccines; surely getting a dead virus is all other things equal very likely much better than getting a live one).

      In any event, the fact is that that alternative will not be provided, and the choice one has to actually make is between vaccines or no vaccines and also no deliberate infection.

      Whether vaccines will be mandated depends on the country, but I xpect that they will be mandated in an increasing number of countries as time goes by and there is better info and better vaccines (though I think they're good enough already). Still, that might take years.

      That aside, with respect to comorbidities, I'd say one has to read the results carefully. For example, if it turns out that 99% of people who die of COVID have comorbidities, but so do 99% of the general population, that does not tell us that comorbidities increase the risk of dying of COVID at all. Generally, how much the risk is increased depends not only on the percentage of people with comorbilities among those hospitalized or dead due to COVID, but also the percentage among the general public.

      In this case, for example for obesity, the cdc says that over 42% of the adult population are obese ( https://www.cdc.gov/obesity/data/adult.html ), whereas the study you linked to says 33% of the adult patients with COVID that required hospitalization are obese. But that's less than among the general population! Given that the researchers reckon that obesity increases risks, I reckon they are measuring obesity in a different manner from the cdc website, but I do not know how they're measuring it, so I do not know how to compare that with the general population.

      While I do not have the time to track down all of the details to compare the actual rate among the general public (and the same for the other conditions in the study about comorbidities), I reckon that that obesity and some other factors do increase the risk of COVID in a significant manner, but I don't know how much they do, so a number like 95% or 98% having comorbidities with no further info does not give me much information about the comparative risks.

  5. PART 1
    Hello again Prof Chappell.
    Concerning your first point ("Hmm, given how much people were freaking out over a 1 in a million chance of blood clots, I don't believe that any fully FDA-approved vaccine would have anything remotely like a "1 in 43 thousand death rate") the claim re 1 in 43,000 was made by Prof Ioannidis who was not suggesting that the particular vaccine not be made available. In fact, he said it is good for Greece to have this vaccine because there are not enough vaccines. I am saying this because i doubt that a scientist of his stature would have made any serious mistake in assessing the study, so if he is saying something mistaken, namely that the risk that the study showed was 1 in 43,000 and that the study was credible then his only other motive must have been to deliberately misrepresent so as to agitate against the particular vaccine. But he clearly speaks supportively of the vaccine, on min 13 00 he says the UK used it with excellent results for those above 30 years old, and that Greece needs it, but that he is wary of using it for younger ages. He does not speak with hostility for the vaccine. But if there is no error in his assessment of the Norway study, and if he has no hard feelings for the particular vaccine, then i can’t see how this study can be dismissed summarily. 1 in 43,000 is an extremely low risk of death anyway. As for the freaking out over the 1 in a million chance of blood clots (Prof Ioannidis says the Norway study calculated a risk of 1 in 26,000 for blood clots), i have no knowledge of the incidents you are referring to, but your point seems to be presupposing (if one interprets charitably the FDA’s standing intentions re vaccine safety) that some extravagant and unwarranted outrage of third parties over vaccine side effects influenced the FDA a lot, so much so that the FDA would be reluctant at a later time to approve any vaccine with a risk of death of 1 in 43 thousand, apparently out of fear of a new backlash (a potential backlash that the FDA feared could damage significantly vaccine acceptance? That’s my charitable interpretation of the FDA’s mindset). And this in turn presupposes that the original extravagant and unwarranted backlash had created a situation conducive to reducing vaccine acceptance. But quite the opposite must have happened: those who are amenable to argument re vaccine safety, i.e. some of the people who only fear that only these vaccines may be risky must have been persuaded that the vaccines are riskless, because indeed a 1 in a million chance of blood clots is tantamount to zero chance, and they must have closed their ears to any possible future screams having seen how extravagant and unwarranted the screams were. As for those who were affected by the screams re the 1-in-a-million chance and decided not to get vaccinated, there was nothing the FDA could ever do to satisfy them, they were lost cases from the beginning, from the perspective of the FDA, as much as conscientious objectors like me are. Therefore the FDA had nothing to lose by licensing a (ex hypothesi) more risky product, given that it had reason to believe that the hypothetical second outcry could not do any damage because there would be very few people in the set of the undecided ones that could be won or lost. To conclude, I do not see the original extravagant outrage against the safety of the vaccine in the way it seems you presuppose, I do not see it as having forced the FDA to be more cautious in its assessments. On the contrary, the extravagant reaction to a near-zero stated risk of blood clots must have helped the FDA’s purpose to increase vaccine acceptance.

    1. PART 2
      On the other hand, In favour of your skepticism about the veridicality of the Norway study is the fact that Prof Ioannidis spoke in April and now it is August, and since then far more data must have been collected, so it could be the case that the risk of death is far lower than the 1 in 43,000, as you imply. But if I were asked if i would trust the FDA (who may include pockets of corruption in it) more than a renowned scientist (Prof Ioannidis) who does not even bother to have a Twitter account, opting instead for writing poetry and literature in his spare time (meaning: he is not a player in any power game), then i trust Professor Ioannidis more (who, by the way, is a vaccine lover; in many of his early references against lockdowns he was making reference to how many essential (according to him) vaccinations were being missed because of the lockdowns. And let’s add to this the fact that he has publicly stated (in Greek) that he believes the Covid vaccines have zero chance of causing bad side effects in the long run). He is not in any way trying to cast doubt on the value of the Covid vaccines. But this means his appeal to the Norway study is a reason for believing that the study was indeed credible. For what it’s worth, the risk of myocarditis that Prof Ioannidis cited in the latest video of his (Aug 24, 2021, min 18:00) is 70 for every million (1 in 15, 000 approximately) but he warns that the danger could be 20-100 times higher than has been recorded in VAERS, as a Harvard study re anaphylactic reactions in mRNA vaccines-reporting shows. But he supports voluntary vaccination because that risk, he states. is very small:

    2. PART 3

      Concerning your second point ( “I gather that the Delta variant is somewhat worse than flu for youngsters (in terms of hospitalization risk)). I don’t know of any very recent study, here is the science journalist I quoted before (Liam Mannix) from his article a few days ago:


      “The evidence remains the same: for children, COVID-19 is a mild illness.
      “In terms of ICU admission and deaths, there is no indication in the data,” says Professor Danchin.”

      I would think death and ICU admissions are better indicators of severity of disease than hospitalizations that are survived without any lasting bad effect on the child. And a more general point considering your tacit point about the flu warranting vaccination: whether for children or adults, it would be good to know what is our personalized risk either from the flu, or Covid or whatever. The State and the medical establishment have not assisted in making salient the importance of this personalization of risk – actually, they were obscuring it. Here is the Oxford Covid risk calculator https://qcovid.org/ (1)(please see the caveat in the footnote before using the Calculator) where after answering the questions about relevant risk factors for Covid death (weight, chronic diseases, age, others) we get the answer (mine is 1 in 14,000. I think that as (and if) the evidence base becomes more enriched with other risk factors (smoking, healthful diet etc) I may even go down to 1 in 140,000. It is a medical fact that the functioning of the immune systems even of similar people differ a lot) But even my present evidence based risk seems negligible-for-me to me, especially given my speculation that there is more chance that natural infection protects better than vaccination against a hypothetical future very dangerous mutation (how would we go about assigning probabilities for such long term eventualities? Or should we give it a 50-50% chance that natural infection is better than vaccination? My coarse and scientifically uninformed intuition that motivates my thinking is “Evolution knows better than scientific design if the agent is healthy”; or, better, “the evolutionary knowledge incorporated in my body already” instead of “Evolution” . For discussion of this intuition, see Dr David Katz’s post with scientifically informed contrarian stance to my intuition re vaccines vs natural infection (2) ). Taking my chances of 1 in 14,000 (very low chances, but, let’s stipulate, higher than my personalized risk of death by the vaccine) by deliberately facing the virus now (in deliberate, supervised or unsupervised natural infection) may be protective (thanks to better mucosal immunity?) against a future monster that the then prevailing vaccine won’t be able to stop before the scientists tweak the vaccine. Seems like insurance to me.

    3. PART 4
      Concerning your other point ( But in principle, sure, it's conceivable that one could make an argument for natural infection based on possible greater protection from worse future variants. In practice I think such a case would be weak because (1) The empirics seem very murky -- early on there were lots of articles talking about how vaccines can provide stronger immunity than natural infection does;) I think we have reached the end point where the conclusion is that we need more public discussions on this by scientists representative of all views. I already voiced some questions of mine pertinent to my attitude towards risk-from-pathogens (how do we assign the probabilities for such long term eventualities? What is the rational response in case we are convinced that Nature does it better but have no clue about how to assign numerical probabilities, or if it is impossible to assign probabilities
      Concerning the next point you made ( “I don't think we need to worry much about future variants because now that the infrastructure is in place, they'll be able to pump out a refined mRNA booster vaccine very swiftly; ) I think this point comes down to the previous point about the murkiness of the empirical knowledge about the benefits of natural infection re future pathogens: if we assume for the sake of argument that natural infection does protect significantly better against certain future variants (as is my initial speculation) then we are assuming that there can be a future variant such that the vaccines will not be able to stop in time (I am referring to those who will die until the new vaccines come out), or maybe even not able to stop adequately (for this second case, I have in mind a new pathogen that, let’s stipulate, can be stopped by the naturally infected due to cross reactivity, but not by the vaccinated. So we are back to your first point, namely that “the empirics are murky”.

      Here is the New Yorker making clear the point about potential problems in delivering the vaccines in time, even after we have committed ourselves to an apparently never ending all-out war against all harmful viruses:


      “the virus could accumulate mutations that allow it to circumvent immunity without suffering a major reduction in transmissibility or lethality. This would require it to open up a new evolutionary space—a citrate moment. Even in this scenario, Burioni [famous Italian virologist] told me, we’re in a fortunate position: we can quickly modify our vaccines to confront new variants. At the same time, the manufacturing and distribution challenges facing those variant-specific boosters would be colossal; we’re struggling to fully vaccinate even a quarter of the world’s population with the vaccines we already have.”

    4. PART 5
      Prof Chappell, here is your final point:

      “ (3) having said that, natural infections are how variants arise and spread, so more widespread vaccination seems helpful to further reduce the population-wide risks here.”

      Your tacit point is that the unvaccinated are both the sole incubators of the new variants, and the ones mostly responsible for the spread
      Charitably interpreted, you are referring only to unplanned natural infections, because if someone is deliberately naturally infected and immediately self-quarantines she does not spread anything. When she gets out of course she will be capable of spreading the virus, in spite of her natural immunity, because no immunity to Covid, is sterilizing immunity, either through infection or through vaccination: both immunities allow for spreading the virus. So we cannot accuse the unvaccinated ones for spreading the virus and ignore the spread from the vaccinated ones. If there are any differences in transmission between vaccinated and unvaccinated due to some or other biomarker (such as less numerous antibodies) then we the deliberately infected can always undergo a booster deliberate natural infection to bring the biomarker to shape.

      So this leaves us with the second point about how variants arise because of the unvaccinated. But the new variants are incubated in both the vaccinated and the unvaccinated, not just the unvaccinated. So it can’t be just the unvaccinated that are the cause of the mutations:


      “During this pandemic, we’ve developed and deployed vaccines in real time. Meanwhile, SARS-CoV-2 is replicating not in a dozen flasks but in tens of millions of people, some of whom have been immunized, all of whom exert selective pressure for the virus to find new, more efficient replication strategies. The virus will continue to mutate every moment of every day, for years, for decades. The fear is that it will hit upon a second citrate moment: a mutation, or set of mutations, that enables it to circumvent our vaccines, which so far have proved spectacularly effective and resilient. For those who remain unvaccinated—the majority of humankind—there is also the horrifying prospect of a variant that is vastly more contagious or deadly. Every few months, we learn of a version of the virus that seems somehow worse: Alpha, Beta, Gamma, Delta. The coronavirus appears destined to march its way through the Greek alphabet—a prizefighter getting quicker, slicker, stronger with each opponent. What are the limits to its evolutionary fitness? Are they knowable? And, if so, how close are we to reaching them?”

    5. PART 6
      Also, Dr David Katz argued in Jan 2021 that by forbidding in the beginning the exposure of those who wanted to be exposed actually gave time to the virus for further mutations. I mean, far from being the villains, people like me who don’t mind the danger posed to us from Covid and are willing to be naturally infected can be heroes under any policy scenario with future pathogens:


      “The only practical way to constrain the impact of mutation with an airborne pathogen that can take refuge in animal reservoirs…is risk-stratified exposure. I won’t belabor this point, because it is now a case of “coulda’, shoulda’, woulda’” of limited practical value. But intentionally high, early exposure among those reliably at the lowest risk of adverse outcomes, followed by those at next lowest risk, and so on…was a way to let the original viral strain produce widespread immunity with minimal harm. The alternative to that- whether with a “lock it all down” slant, or a “liberate it all” slant, is much the same: haphazard exposure in the absence of risk stratification and risk management. The wait for the vaccine, though rewarded with such prizes in record time, nonetheless accorded the virus far more time than required for innumerable mutations, and for those favoring more viral propagation to disperse and predominate.”

      Finally, here is a Professor of Infectious Disease Ecology, Hamish McCallum, who flatly states that the variants that will be doing the killing (is he referring to the so-called variants of concern (VOCs)? ) will be arising in the vaccinated ones, not in the unvaccinated ( I don’t fully understand the mechanism he describes re the tradeoff between virulence and transmissibility, so I am just parroting his words and take his conclusion for granted for the sake of argument. His conclusion was what I was silently speculating all along but afraid to say):


      “COVID-19 vaccines reduce your chance of transmitting the virus to others, but they don’t totally block transmission. And evolutionary theory gives us a cautionary tale.
      There’s a trade-off between transmissibility and how sick a person gets (virulence) with most disease-causing microorganisms. This is because you need a certain viral load to be able to transmit.
      If vaccines are not 100% effective in blocking transmission, we can expect a shift in the trade-off towards higher virulence. In other words, a side-effect of the virus being able to transmit from vaccinated people is, over time, the theory predicts it will become more harmful to unvaccinated people.”

      Therefore there is scientific opposition to the claim that the genesis of the variants is caused by the unvaccinated only. If there is some evidence that supports the idea that the new variants are born in unvaccinated only (naturally immunized or not) rather than in the vaccinated I would like to know.

    6. Footnotes
      1: the calculator of the Oxford University explicitly and strongly warns against using it in the way I did, i.e. for assessing my personal risk:

      This implementation of the QCovid risk calculator is NOT intended for use supporting or informing clinical decision-making. It is ONLY to be used for academic research, peer review and validation purposes, and it must NOT be used with data or information relating to any individual.

      2: Dr Katz’s discussion of Evolution vs Scientific Design. I side with Evolution, call me religious if you will 😊



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