“Living with Covid” Interesting paper on tradeoffs

Here is a new paper from Imperial College, this time by a team with David Miles, Mike Stedman, and Adrian Heald, looking into the implicit cost per QALY that the UK spent via lock downs and other repression policies. They use a somewhat different methodology from mine, estimating marginal effects of policies from cross-country variation rather than with some notion of the previous status quo, but they end up with almost the exact same answer that “The lowest estimate for lockdown costs incurred was 50% higher than highest benefits from avoiding the worst mortality case scenario at full life expectancy tariff and in more realistic estimation they were over 50 times higher“. In other words, they estimate that for every life-year saved by restrictions, an estimated 50 will be lost down the line whom we can no longer afford to save. And that’s just solely within the UK. They hence say it was all a huge mistake that we should undo as fast as possible. Here’s their full abstract:

The COVID-19 pandemic has transformed lives across the world. In the UK there has been a public health driven policy of population ‘lockdown’ that had enormous personal and economic impact. We compare UK response/outcomes including excess deaths with European countries with similar levels of income/healthcare resources. We calibrate estimates of the economic costs as different %loss in GDP against possible benefits of avoiding life years lost, for different scenarios where local COVID-19 mortality/comorbidity rates were used to calculate the loss in life expectancy. We apply quality-adjusted life years (QALY) value of £30,000 (maximum under NICE guidelines). The implications for future lockdown easing policy in the UK are also evaluated. The spread of cases across European countries was extremely rapid. There was significant variation both in severity and timing of both implementation and subsequent reductions in social restrictions. There was less variation in the trajectory of mortality rates and excess deaths, which have fallen across all countries during May/June 2020. The average age at death and life expectancy loss for non-COVID-19 was 79.1 and 11.4years respectively while COVID-19 were 80.4 and 10.1years; including for life-shortening comorbidities and quality of life reduced this to 5QALY for each COVID-19 death. The lowest estimate for lockdown costs incurred was 50% higher than highest benefits from avoiding the worst mortality case scenario at full life expectancy tariff and in more realistic estimation they were over 50 times higher. Application to potential future scenarios showed in the best case a QALY value of £220k (7xNICE guideline) and in the worst-case £3.7m (125xNICE guideline) was needed to justify the continuation of the lockdown. The evidence suggests that the costs of continuing severe restrictions in the UK are so great relative to likely benefits in numbers of lives saved so that a substantial easing in restrictions is now warranted.

 

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53 Responses to “Living with Covid” Interesting paper on tradeoffs

  1. paul frijters says:

    here’s a whole UK website which runs analysis after analysis on the horrendous cost of the UK’s policies: https://lockdownsceptics.org/
    When reading the various articles on it, it feels like walking into a pub where everyone agrees with everything we’ve been arguing here at Troppo for three months, but the contributors all add their own perspective and unique knowledge as well. Refreshing.

  2. paul frijters says:

    Here’s the main website on the excess deaths in Europe, tracking the regular mortality rates in over 24 countries, starting in 2016, so you get to see the previous flu-seasons of 2018 and 2019. The graphs basically show the covid-19 wave in Europe is over and was not much bigger than previous flu-waves. https://www.euromomo.eu/graphs-and-maps#

    Interesting points to note:
    – the total excess deaths relative to the same date in 2018 are about 80,000 people (now even declining). Since the data represent about 350 million people, that’s a total mortality rate of 0.023% above the 2018 flu-season (which was a relatively bad year). Its 0.06% relative to “baseline” (essentially the decade before 2016). Basically an extra week or two of normal mortality rates.
    – there is no clear second wave anywhere in Europe, despite places open for over a month now (Switserland). Belgium and Spain show weak hints of a second wave.
    – Sweden had unusually low-mortality flu-seasons in 2017-2019 relative to the rest of Europe.
    – these excess deaths are all-causes, so will include any deaths from people with other illnesses who didn’t get the necessary treatments because hospital operations were cancelled or whatnot. Hence, so far, stories of masses of Europeans dying from other preventable causes don’t seem correct either. The lack of continued spikes for the elderly is in line with this: if there is a longer-term loss from lack of normal care, it will be of the preventative kind that will take a much longer time to show itself (and will thus be hard to causally prove).
    – the pattern between previous flu seasons and this one is not so clear. You’d think that places with clear previous higher-than-ordinary flu-season deaths would have a low current first-wave, but you dont see that. Berlin had no noticable previous wave or current wave. Spain had quite pronounced previous seasonal waves, and did so again this time round. The UK, Netherlands, and Sweden had little in terms of strong previous waves, but a pronounced wave now. This means stories on previous immunity build up via other flu-waves are hard to maintain unless that previous immunity comes from “regular waves” that are in the baseline, come from further back than 2016 or are due more due to continuous infections rather than abnormal seasonal waves.

  3. Paul
    Significant stuff:
    Prof Keith Neal, Emeritus Professor of the Epidemiology of Infectious Diseases, University of Nottingham, said:

    On “Fortieth SAGE meeting on COVID-19, 4th June document”

    “The SAGE meeting notes from the 4th June on the situation update make interesting reading. Numbers 5,6 and 7.

    “They confirm that a significant amount of the total cases are acquired in hospitals or care homes. Including these cases in overall community models is highly inappropriate as control of COVID-19 is different for the different routes. Social distancing in all it’s nuances for the community and infection control in hospitals and care homes. When meat plant and similar outbreaks are added into the R currently being published there will be further distortion as these are managed as specific outbreaks, not more social distancing.

    “The fact that models (on 4th June) were reporting 35,000 cases daily compared to actual people based methods such as the ONS and the Zoe app of 7-8000 is clearly worrying. They can NOT both be right and highlights the problems for the decision makers with such disparate key information.”

  4. Kien Choong says:

    In a recent LSE podcast, Tim Beasley said that the containment policies involved a huge distributional shift from the young to the old. That claim wasn’t disputed by other presenters/commentators in the LSE podcast.

    If this distributional issue had more attention in public discourse (and the media), I wonder what effect it would have on policy.

  5. paul frijters says:

    https://www.medrxiv.org/content/10.1101/2020.06.21.20132449v1

    Here’s an interesting little study that should have gotten a lot more attention because it is saying something important that I have been saying for months: many people catch this virus but do not show up positive on those anti-body tests. Rather, their immune systems deal with it in other way. You might say they shrug it off. Or that the T-cells take care of it. This little study found a family of 8 who had all contracted the virus (something you can measure if you’re there at the start), but in a follow-up only 2 out of the 8 developed anti-bodies and 6 out of the 8 did not (but did have a T-cell response).

    That’s just huge. It’s exactly the ratio you’d expect from the Diamond Princess data where only 700 out of 3,700 showed up positive in ex-post tests, but where everyone surely got some exposure.

    It would mean the serology tests underestimate the percentage of the population that have had it by a factor of 4. Multiply the estimates on serology by 4 and you are close to herd-immunity already in many countries and cities in Europe. All you need to add on that is some prior immunity via other diseases and you explain the lack of second waves. This should be headline news. It suggests the corona outbreak in Europe might truly be almost over and will only return in countries that had an insufficiently small first wave, like maybe Germany.

    • Aaron says:

      Why haven’t such studies been conducted on a larger sample size?

      I’ve heard lots of people talking about other forms of immunity, yet I’m seeing very little research being done to validate this. Everyone is solely focused on antibodies.

      • paul frijters says:

        Hi Aaron,

        maybe it has been done on bigger samples, I dont know for certain. There is now so much coming out at such a pace that we might simply not have heard about it yet.

        There is another element though, which is that scientific training has become very narrow in recent decades. There are now hordes of scientists raised with the idea that if it hasn’t been shown to exist in a randomised trial or via some trusted test, then the status quo belief must be presumed to hold. So information like “those other passengers were surely exposed so the tests dont pick up everything you want to” is a kind of data and thinking no longer taught or appreciated. It doesnt fit the canon. But its exactly that kind of thinking and data that leads to new hypotheses and that good model builders look for.

      • Conrad
        It is possible that for ,possibly multiple different reasons in some people the virus struggles to get a foothold in the first place.
        For example there is a hypothesis that in some people their ACE2 receptors are less receptive of the virus .
        https://journals.sagepub.com/doi/10.1177/2040622320935765

        • Conrad says:

          I’m sure there must be — What I don’t really understand is when they say you lose immunity to what extent you lose it all. Surely it can’t be all otherwise every new encounter would be completely novel — or can it?

          The above comment was just to note that if you predict 3 cases going missing for every one found, the most you can ever predict is 25% found. If you assume herd immunity then a result of 43% missing means the most you could be missing is 1 for each found (giving 86% immunity).

          • It could be like the flu most of the time you have some kind of resistance ;most of the flu’ I’ve had were relatively mild. but sometimes something really gets through the defences; when I was 35 I had a flu that knocked the crap out of me ; for about ten days I could barely get out of bed , I went from weighing about 68 kilos to weighing just 58 kilos , i looked like I’d come out of Changi.

      • paul frijters says:

        funnily enough, I brought up the exact same numbers as the main “problem data” about a month ago when discussing this issue (in one of my herd-immunity posts). I then also argued that the 50% serology test rates in some NY neighbourhoods made the “other immunity” story harder. Now I think there’s enough evidence of various sorts (small studies, slowing death rates, lack of second waves, regional puzzles, children) to suggest one should look for other explanations for those NY neighbourhoods rather than doubt the “other immunity” story.

        Maybe the ventilation in those NY neighbourhoods is so poor that they got deep infections there (because we know almost everyone who has had this thing in a bad way gets anti-bodies). Maybe some previous viruses passed those neighbourhoods by. Maybe there is a genetic component. We dont know. But there are further dimensions to play with on this.

        • Conrad says:

          I’m not quite sure what you can infer from NY given it was only very recently let out of serious lockdown and, as far as I am aware, people are still pretty restricted by rules, as well as self restricted (wearing masks etc.). That being said, they never stopped getting 1K cases a day, which is hard to reconcile with herd immunity. I assume you’ll admit you are wrong if the numbers go up again and I’ll admit there is more to it if the state stops enforcing rules and people give up being careful (like happening now in many states in the US), and the cases go down.

          It’s funny that you should talk about air-conditioning and randomized trials. These first of these I brought up (possibly on Facebook), and no-one thought anything of it, despite it being a likely factor in some cases of SARs-1 (including one major outbreak). As you may know, I also don’t think too highly of randomized trials (often a waste of money run that could be better on smaller scale theoretically motivated experiments). However, in this case, I don’t think it is too bad because quantitatively, it bounds both the top-end and bottom-end, which is useful for planning. I also think it’s up to people like you arguing for an anomaly for telling us what the reason is that your prediction is out by 300%, as that is clearly a huge effect size, and so tiny factors are not going to cut-it. So good luck finding them.

          On that note, it is pity there is no big data collation site as I think many of the possibilities could be answered. For example, at least for the data here, it should be easy to tell if it is (a) a built-up neighborhood effect (there are many which called be compared); (b) an African American effect (there a largely white states going through the roof right now like Arizona, so perhaps that will be answered soon); (c) a low-SES effect; or (d) a obesity/poor health effect.

        • Aaron says:

          I saw this study that finds the antibodies drop off after 2 to 3 months: https://www.nature.com/articles/s41591-020-0965-6

          This might explain some of what’s going on. Not entirely clear what the implications of this are: whether immunity is short lived, or whether immunity is present through T cells even after the antibodies drop off. It seems unlikely to me that these people are all susceptible again because we’d be seeing lots of reinfections by now, given that we’re 6+ months into this.

          • yes, indeed, another article saying the serology tests miss people who had been infected, even a few of the symptomatic cases. Quite a few more of the asymptomatic, relatively quickly. The timing aspect creates another twist in this puzzle. Working out the true number who were infected at what time would then need a whole path of data to reverse-engineer.
            And of course this is based on those picked up by other tests. Less severe cases again might show yet other variations. This is one tricky disease. Standard cases hardly exist it would seem. So much individual and contextual circumstances of importance: infection level depending on ventilation, humidity, length of exposure. Then individual immunity characteristics, involving prior related diseases, age. Then testing outcomes depending on timing, place of testing (nose, blood).

            Easy to get the propagation and mortality rates very wrong when so many things matter. Only large-scale real outcomes can then tell you how lethal it is overall. On the memory of the body against it, drops in anti-bodies suggest some forgetting, but then the link between previous related diseases suggest some longer-term remembering as well. And of course, once you’ve had it, this virus is probably a reasonably effective vaccine for itself at low doses.

            This is going to be very difficult to explain to the general public.

            • Conrad says:

              The levels of false negatives are nothing like you are claiming.

            • Aaron says:

              Paul – I wouldn’t be surprised if other respiratory viruses have similar properties. They simply don’t get so much scrutiny, so we don’t know. I think you’re absolutely right that only large-scale real world outcomes can tell the true story. We really want the total population fatality rate.

              The mathematical models are all very well, but they simply don’t work here. Michael Levitt’s curve fitting sounds more and more compelling to me than any of these junk models.

        • It would seem that NY like the UK transferred significant numbers of ‘burning embers ‘ from its hospitals to aged care facilities…
          https://apnews.com/4042f05613ee4259b7a44d4466a0a02a

  6. Maybe of interest
    Prof Neil Pearce, Professor of Epidemiology and Biostatistics, London School of Hygiene & Tropical Medicine (LSHTM), said:

    “This updated report from ONS strengthens the evidence that, for working age people, COVID-19 is largely an occupational disease. The occupations which are at increased risk are those which involve regular contact with patients or the public. These include security guards, taxi drivers, bus drivers, chefs, and sales and retail workers. All of these occupations should be supplied with appropriate PPE and required to use it – this is a workplace health and safety issue. It is not just health and social care workers who need PPE – it is anyone working with the public.

    “As you would expect, there are also increased risks for social care workers. However, the rates are not so high for health care workers. This probably reflects a major problem with the data that ONS has to work with. For this group, many probable Covid-19 deaths are being referred to Coroners. In England and Wales, these deaths are not ‘counted’ until the Coroner has completed their investigation – which can take months or even years. In the meantime, these deaths don’t appear in the official statistics. This problem doesn’t happen in Scotland because act-of-death must by law be registered within 8 days of death having been ascertained. An emergency system should be in place in England and Wales so that the Office for National Statistics is informed immediately about any death referred to coroners so that fact-of-death is registered.”

    “Coronavirus (COVID-19) related deaths by occupation, England and Wales: deaths registered up to and including 25 May 2020” was publsihed by the Office for National Statistics on Friday 26 June

    https://www.ons.gov.uk/releases/coronaviruscovid19relateddeathsbyoccupationenglandandwalesdeathsregistereduptoandincluding25may2020

  7. Conrad
    Penny for your thoughts seems plausible that some may have been exposed to an earlier ancestor of Covid19 ( many of the people I know last year had some kind of viral thing that left them very tired for months)
    https://www.biorxiv.org/content/10.1101/2020.06.22.165787v1

  8. Aaron says:

    Just read about this: https://news.ki.se/immunity-to-covid-19-is-probably-higher-than-tests-have-shown

    It’s supposed to be available as a pre-print soon.

    “Our results indicate that roughly twice as many people have developed T-cell immunity compared with those who we can detect antibodies in.”

    • paul frijters says:

      thanks for digging this up. Circumstancial evidence has been pointing to this for months, but only small studies. This is a reasonably big study. The headline number is that according to them 30% of the blood donors had a T-cell immunity in May. So that’s after getting ill maybe 2 weeks before (T-cell immunity is not immediate either). Fast-forward that to the present day with the rate of observed cases and Sweden must have something like 60% immunity (at least among the clientele of the blood bank). So they are there! Other countries will basically play catch-up.

      So a total fatality rate of maybe 0.06% is the price this virus enacts in Sweden. 1 in 17,000. The normal fatality of 2-3 weeks.

      It’s got to be possible to achieve herd immunity quicker with less deaths (and less socio-economic disruption).

      • Conrad says:

        I don’t really see how they are “there”. The numbers are still going up. Surely you should see an asymptote and a reversal. Why has it become easier to catch the virus?

        Apart from that, people were claiming 20% in Stockholm some time ago, so the number is not much different to what the previous tests were saying, despite the claim they are missing a whole lot of people.

        You might like to consider the sample too. I don’t what percentage of people think it’s a good idea to go to a hospital in the middle of a pandemic to donate blood (I can certainly resist), but presumably this is a high risk group, and not the people staying at home. People were dieing here because they wouldn’t go to emergency.

        • if you look at the test and death data in Sweden you see a huge upswing of mild cases and a continued reduction in numbers of deaths or even critical cases (only 170 of those last time I looked). They, like places in the US and Brazil have changed test regimes and are seeing this huge upswing in those positively tested, so I dont put much faith in the changes in tested positive as an indication of much of anything, but I suspect its just about different test regimes, not a real increase in actual cases. I knew the hysterics are doing their usual spiel on it, but at some point the narrative is going to flip to its opposite: huge numbers of positive tests and almost no deaths tell you how innocuous this thing is for the vast majority.

          Now, the 20% was basically a serology-test projection for early June. 60% would mean double to trebble that projection. A bit less than the 1 to 4 I have been using in the back of my mind sofar, but definitely the right ballpark. And dont forget, you probably need about 80% for herd immunity so you’d expect quite a lot of active cases in the months that the population is going from 40% to 80%. So I dont see a contradiction at all. On the contrary. The main thing to note is that they seem to managed to shield the most vulnerable population (or they have only a few of those left) from the ongoing wave.

          I still think Sweden has been far too reckless in the authorities telling the population to voluntarily distance. I think they would have gotten it all over with much quicker with fewer casualties and less socio-economic disruption if they’d have told the vast majority to get on with normal life, only making some arrangements for the most vulnerable (on a voluntary basis!).

          Its Germany and the other Scandinavian countries that are a bit of a puzzle. Did they have prior immunity unbeknown to them or do they still have a largely vulnerable population? I am sure various groups are trying to figure this out as we speak. This is the sort of thing science eventually gets right.

          • Conrad says:

            I agree some of the difference is likely to come from more testing.

            However your statement here is really empirical: “huge numbers of positive tests and almost no deaths tell you how innocuous this thing is for the vast majority”

            The alternative is that people who are in danger (which on current wisdom is, I guess, people > 55 or people with other diseases) or who have enough worries about it (like a fair chunk of the world) minimise their risk. Perhaps we don’t care about the latter, but the other group forms a decent chunk of the population (even obese people alone do in some places). I imagine avoidence would be pretty easy in Sweden compared to many places which are much more built up (or perhaps it’s my imagined stereotype).

            Also, given all the weird symptoms people are getting (including younger people), we don’t really know how innocuous it is, even if the death rate is as you claim (and that would be especially the case if it ends up that we don’t get reasonably long immunity to it — hopefully we do given it is clearer tougher on people’s immune systems than a common cold, but who knows). So people have some reason to worry about it.

            • oh, I am definitely making empirical statements here which means I can be proven wrong. I have been making empirical statements for months, particularly my 0.2% which is looking ever more overly pessimistic by the day.
              On the testing, its not just a question of more of them. It’s also a question of how well they pick up even low infection level. And there are many questions of administration at least as important. For instance, a health authority looking to maximise the information on the spread, uses the tests it has to randomly tests over the populations it want to keep track of. A health authority less interested in tracking changes but more into being seen to find cases would, for instance, give into the pressures from households wherein one person is found to be positive to test the rest of the household. A couple of positives virtually guaranteed, and the household members involved will want them. One can probably treble the number of positive cases per test just by that admin rule alone (ie testing the others in a household with a positive case).
              There are other admin issues. Test regimes are quite decentralised, so lots of different rules apply as to who gets them and who is gets forced to take them. Those rules will change over time with cost, availability, remuneration, demands from employers, etc.

              God knows what all that does to the number of positive tests over time versus actual cases. Too many free parameters to keep tabs on, and no one seems to keep tabs. I have not found an article or website that has tried to track the admin around these tests. Its possible no-one knows. So I discount the information in those tests very heavily, particularly for places where we know from the serology and T-tests that there is a huge population that has got to have had this thing, much, much higher than shown in direct tests of infections.

              • Aaron says:

                Yes, the number of cases is a totally meaningless metric, yet the media is obsessed with it. I really don’t know what has gotten into people because the death rate is dropping in the US while cases are rising and various states are rolling back into forms of lockdown. Bars and beaches closed in some states, restaurants closed back down. It almost feels like they want to keep everyone in fear and keep doing cyclical lockdowns until there’s a vaccine or we get to zero cases. The whole thing is out of control.

                • yes, as I said in my “5 surprises post”, the ongoing popularity of draconian policies is the biggest surprise. The grasping on the fear as something to be desired and held onto. It now seems it will get Biden elected.
                  But, once again, my hope is competition. No matter how strange some states and people get, the sight of others enjoying life more is a powerful tug.

                  The UK is still outlawing fun at marriages, meaningful football (you know, with a crowd), real parties (with toilets and close-formation dancing), etc. And its not just the conservatives either. The Scottish National Party, rulers of Scotland, are making it their business to be even more totalitarian than England. They are, dont laugh, talking about eliminating, but not eradicating, that virus (wow! You cant make it up.). Wales, also not run by conservatives, is in competition with Scotland for who can be most prescriptiveand destructive towards its own economy. I feel like Alice in Wonderland.

                  • Aaron says:

                    Who is actually enjoying life I wonder? I don’t see any state going back to normal, not even NY. Or even Italy for that matter. It seems they’ll keep the economy half-alive and not care about people’s happiness one bit, and this will continue until a vaccine is found.

                    The only places I can think of right now are unlikely spots like Serbia or Tanzania, but going there isn’t exactly very appealing. Sweden isn’t letting in foreigners. It feels we’re going to be stuck in this insanity for years.

                    And yes Biden will be re-elected most likely.

                    • good question. Who is enjoying life? I suspect several hundred million holiday planners will want to go there!
                      In all honestly, I think Southern Europe (Greece, Italy, Spain) is re-discovering its joie de vivre. The Netherlands is regaining it. The “lower classes” in the UK seem to be trying with all sorts of illegal raves and parties. The Swiss.

                      Is there really no place in the US that is resisting all the bs and is trying to hang on to the joy of life? Some hippie community in California must be holding on to its principles. No?

                  • Aaron says:

                    The column width keeps shrinking. I wonder if you can change the comment formatting. Anyway, to answer your question: Georgia and South Dakota are staying the course. Might consider them.. but some of the photos/videos from Serbia do look quite nice. If they are real, then it appears they are totally back to normal..

            • Conrad says:

              Sorry about the graph being on Dan Andrew’s Facebook page, but here’s a good example of behavioral change and what it means to your inferences. These are the new cases from Victoria and what age they are.

              https://www.facebook.com/DanielAndrewsMP/photos/a.149185875145957/3202194336511747/?type=3&theater

              You can see, almost no infections in people from 65 and over. This suggests that people likely to get bad outcomes from Covid have modified their behavior to avoid it and/or people who think they are not at risk are taking more risks. If you didn’t know this and calculated the death data from it (which will presumably be very small), you would clearly underestimate the danger of the virus. Indeed, any data collected apart from random samples is going to be problematic because of what looks to be a behavioral change in a large proportion of the population.

          • Conrad says:

            By the way, one reason I haven’t commented on the T cell stuff is that I don’t what the false-positive/negative rate is. For example, you seem to assume it is perfect as far as I can tell — but I am not sure how one knows this.

  9. Conrad says:

    Try looking at Table S1. I flicked through that, and I am not sure where this double figure comes from — If you look at the ACUTE patients here, of which there are all of 10 in the moderate group, only 5 show antibodies (50%), so perhaps it is there (but I doubt it this because we know the tests only sensitive after some time). If you look at the COVALESCENT group, i.e., those that are recovering and thus have had the virus for some time, the identification rate is 85% for those even in the moderate group.

    Perhaps they are talking about the exposed relative group, which at 64% is closer to double (certainly not quadruple), but it isn’t clear that they all even had Covid responses of any type (“Anamnestic responses in the CD4+ and CD8+ T cell compartments, quantified as a function of CTVlow IFN-g+ events (Figure 4A), were detected in most convalescent individuals and exposed family members (Figure 4B, C).”. So if you add a bit for “most” you are getting a smaller effect again. Apart from that, as they note: “It remains to be determined if a robust memory T cell response in the absence of detectable circulating antibodies can protect against SARS-CoV-2.” which seems important to investigate.

    • paul frijters says:

      he is just noting, like me, that Germany has an unusually low number of covid-deaths and that “something we dont yet see” might be going on. I too have speculated that it might be prior immunity from a related virus, in which you might say they are lucky now, though of course unlucky at a prior point in time.

      However, you cant see a major prior wave since 2016 in the excess death graphs (link above). So alternatively, we might find out that Germany is a victim of its supposed initial “success” and that it now has very little immunity to the disease so that it will either have to allow a real wave to pass over it, or muddle on till the vaccine comes with suppression strategies at huge ongoing social and economic cost. The same choice is faced by Australia.

      • Conrad says:

        Alternative, and presumably with quite a reasonable probability, both won’t have any great immunity, something that should be factored into current calculations.

    • https://www.sciencemediacentre.org/expert-reaction-to-preprint-paper-looking-at-t-cell-response-in-people-with-mild-or-asymptomatic-covid-19/

      Prof Francois Balloux, Professor of Computational Systems Biology and Director of UCL Genetics Institute, University College London (UCL), said:

      (Comment more generally on T-cell responses)

      “Over the last weeks, a substantial amount of new evidence has become available about immunity to SARSCoV2. This information can be difficult to process and integrate.

      “The immune system is highly complex and comprises a series of different arms. Innate immunity represents mostly first-line responses with no memory of prior infections. Acquired immunity can be broken down into ‘antibody-mediated’ and ‘T-cell-mediated’ immunity.

      Antibody-mediated (humoral) immunity is based on B‐lymphocytes that are reactivated to produce antibodies when exposed to a pathogen upon reinfection. Until recently, all the attention in the SARSCoV2 debate has been on antibodies.

      “Antibodies are fairly easy to quantify which is the basis of serological tests that inform whether someone has been infected with SARSCoV2. Though, it is becoming apparent that not everyone infected mounts detectable levels of antibodies.

      “Antibody levels to SARSCoV2 also wane fairly fast, in line with other coronaviruses. As such, antibody tests can fail to detect prior infection in particular for asymptomatic or mild infections. Serological surveys may underestimate the proportion of people infected.

      “T-cell-mediated immunity against SARSCoV2 has received little attention until recently. The main reasons are that T-cell response is less straightforward to measure and it is generally considered less important for vaccine efficacy.

      “T-cell response is a late immune response and does not generally make the host refractory to infection. As such, a vaccine blocking infection would need to elicit a strong antibody-mediated response. Though, T-cell immunity is essential for controlling an infection and reducing symptoms. SARSCoV2 seems to elicit robust T-cell response even in asymptomatic/mild patients. There is also evidence for widespread cross-immunity with ‘common cold’ coronaviruses.

      “There are four known coronaviruses (229E, NL63, OC43, and HKU1) that cause 15-30% of “common colds”. They circulate primarily in young children. Most people get infected with one or more of these viruses at some point in their lives.

      “In contrast to antibody-mediated immunity, T-cell response is extremely long-lived. For example, people infected in 2003 with SARS (SARSCoV1 ) still mount a robust T-cell immune response to SARSCoV2 17 years later, which suggests they should be largely protected from developing severe symptoms when infected with SARSCoV2.

      “While there is still no established case of SARSCoV2 reinfection to date, it is likely those will be observed soon due to fairly fast waning antibodies. Though, anyone with a prior exposure to SARSCoV2 is expected to experience far less severe symptoms upon reinfection.

      “Most ‘hight-tech’ vaccines tend to focus on eliciting narrow antibody responses as they generally target a single SARSCoV2 protein. Such vaccines are not expected to generate a robust T-cell response. Indeed, T-cell-mediated immunity works best when a host is exposed to the entire diversity of a virus. This raises the question whether there should not be more efforts towards ‘traditional’ vaccines (i.e. attenuated/inactivated).”

      • Conrad says:

        Interesting for lots reasons. I like this one the best, mainly out of self interest: “There is also evidence for widespread cross-immunity with ‘common cold’ coronaviruses”. I might stop complaining that it appears the main goal of childcare is to make your children and then parents sick :).

        One interesting thing would be to look at parents with young children and childcare workers who are exposed to these viruses constantly and see how they went with Covid. One might also expect that people in countries with more children that roam more freely might also get some extra protection by being to exposed to more germs more often.

        • re “ T-cell-mediated immunity against SARSCoV2 has received little attention until recently. The main reasons are that T-cell response is less straightforward to measure and it is generally considered less important for vaccine efficacy.”
          Another aspect could be that vaccines can be patented, on the other hand can Tcell related stuff be patented ?

      • very interesting. Thanks for digging this up. Nice to hear someone who knows a lot about the immune system putting the various immunity issues into perspective. His comments on the potentially limited use of the vaccines being made is particularly interesting. We’ll get to hear a lot more about all this in the mainstream media, rest assured.

  10. Prof Mark Woolhouse, Professor of Infectious Disease Epidemiology, University of Edinburgh, said:

    “The Independent SAGE report proposes a strategy of COVID-19 “elimination” from the British Isles. Elimination means zero cases. This is a worthy but extremely ambitious aim; neither China nor South Korea has yet achieved elimination, and they were the first countries to bring their COVID-19 epidemics under control. To achieve elimination for the UK and Ireland within a reasonable time frame would presumably require a contact tracing system as good as South Korea’s and a lockdown as strict as China’s. The former is already UK government policy but the latter is not; every country in the British Isles is currently attempting to relax lockdown as quickly and as safely as possible.

    “Given the enormous challenge of achieving elimination the key questions are ‘how long would elimination take?’ and ‘how much additional damage would be done by extending the lockdown for that period?’. Before an elimination strategy is attempted it would be sensible to have answers to those questions. The Independent SAGE report does not provide them.

    “The long term vision of the elimination strategy is equally unclear. There is no prospect of eradicating COVID-19 from the whole world in the foreseeable future. Even with a highly effective vaccine, this would be a huge challenge. So we may arrive at a position where regions of the world (small or large) have achieved elimination or something close to it, but the remainder have not. That dichotomy could only be sustained through extremely rigorous travel restrictions and quarantine regulations. New Zealand, currently the country closest to elimination, is already grappling with the implications of this for its tourism and higher education sectors.

    “We need to think very carefully before embracing any COVID-19 response strategy that could result in more long term damage than can be justified by the public health gain. This is the case for any strategy to respond to this pandemic. The worrying truth is that, as of now, none of the available options are the least bit attractive. For all that we have been through in the past few months, the full impact of the COVID-19 pandemic is still to be felt.”

    “The Independent SAGE report proposes a strategy of COVID-19 “elimination” from the British Isles. Elimination means zero cases. This is a worthy but extremely ambitious aim; neither China nor South Korea has yet achieved elimination, and they were the first countries to bring their COVID-19 epidemics under control. To achieve elimination for the UK and Ireland within a reasonable time frame would presumably require a contact tracing system as good as South Korea’s and a lockdown as strict as China’s. The former is already UK government policy but the latter is not; every country in the British Isles is currently attempting to relax lockdown as quickly and as safely as possible.

    “Given the enormous challenge of achieving elimination the key questions are ‘how long would elimination take?’ and ‘how much additional damage would be done by extending the lockdown for that period?’. Before an elimination strategy is attempted it would be sensible to have answers to those questions. The Independent SAGE report does not provide them.

    “The long term vision of the elimination strategy is equally unclear. There is no prospect of eradicating COVID-19 from the whole world in the foreseeable future. Even with a highly effective vaccine, this would be a huge challenge. So we may arrive at a position where regions of the world (small or large) have achieved elimination or something close to it, but the remainder have not. That dichotomy could only be sustained through extremely rigorous travel restrictions and quarantine regulations. New Zealand, currently the country closest to elimination, is already grappling with the implications of this for its tourism and higher education sectors.

    We need to think very carefully before embracing any COVID-19 response strategy that could result in more long term damage than can be justified by the public health gain. This is the case for any strategy to respond to this pandemic. The worrying truth is that, as of now, none of the available options are the least bit attractive. For all that we have been through in the past few months, the full impact of the COVID-19 pandemic is still to be felt.”

    https://www.sciencemediacentre.org/expert-reaction-to-commentary-about-potential-airborne-transmission-of-the-sars-cov-2-virus/

    • this is obvious stuff. You’d think high-school stuff. But apparently not. Here we are still, 5 months in. Sigh.

      • Paul
        “ The worrying truth is that, as of now, none of the available options are the least bit attractive. ”
        That’s so true, I can’t blame our leaders for opting for at least appearing to know what they are doing, opting for dramatic symbolic crap.

        Conrad
        If the figures in the lancet piece you referenced are a true indication of the total number of infections in Spain then surely Covid19 is not that, infectious , needs special circumstances ?

        • Conrad says:

          I would have thought the opposite — 5 million out of about 47 million people — despite a severe lockdown, a population that doesn’t want to catch it too much (c.f., the US where people won’t even wear masks in many places), and a population that is relatively spread out compared to many other places.

          One of the nice things about the paper is you can see how much difference this makes — the provinces which are more sparsely populated have very low rates.

  11. A interesting read
    https://forecasters.org/wp-content/uploads/Ioannidisetal25062020-1.pdf

    Forecasting for COVID-19 has failed
    John P.A. Ioannidis (1), Sally Cripps (2), Martin A. Tanner (3)
    (1) Stanford Prevention Research Center, Department of Medicine, and Departments of Epidemiology and Population Health, of Biomedical Data Science, and of Statistics, Stanford University, and Meta-Research Innovation Center at Stanford (METRICS), Stanford, California, USA
    (2) School of Mathematics and Statistics, The University of Sydney and Data Analytics for Resources and Environments (DARE) Australian Research Council, Sydney, Australia
    (3) Department of Statistics, Northwestern University, Evanston, Illinois, U

    ABSTRACT
    Epidemic forecasting has a dubious track-record, and its failures became more prominent with COVID-19. Poor data input, wrong modeling assumptions, high sensitivity of estimates, lack of incorporation of epidemiological features, poor past evidence on effects of available interventions, lack of transparency, errors, lack of determinacy, looking at only one or a few dimensions of the problem at hand, lack of expertise in crucial disciplines, groupthink and bandwagon effects and selective reporting are some of the causes of these failures. Nevertheless, epidemic forecasting is unlikely to be abandoned. Some (but not all) of these problems can be fixed. Careful modeling of predictive distributions rather than focusing on point estimates, considering multiple dimensions of impact, and continuously reappraising models based on their validated performance may help. If extreme values are considered, extremes should be considered for the consequences of multiple dimensions of impact so as to continuously calibrate predictive insights and decision-making.

    • From the above paper.
      Box 1. John Ioannidis: a fool’s confession and dissection of a forecasting failure

      “If I were to make an informed estimate based on the limited testing data we have, I would say that COVID-19 will result in fewer than 40,000 deaths this season in the USA” – my quote appeared on April 9 in CNN and Washington Post based on a discussion with Fareed Zakaria a few days earlier. Fareed is an amazingly charismatic person and our discussion covered a broad space. While we had focused more on the need for better data, when he sent me the quote that he planned to use, I sadly behaved like an expert and endorsed it. Journalists and the public want certainty, even when there is no certainty.

      Here is an effort to dissect why I was so wrong. Behaving like an expert (i.e. a fool) was clearly the main reason. But there were additional contributing reasons. When I made that tentative quote, I had not considered the impact of the new case definition of COVID-19 and COVID-19 becoming a notifiable
      46 38 despite being aware of the Italian experience where almost all counted “COVID-19 deaths”disease, had also other concomitant causes of death/comorbidities. “COVID-19 death” now includes not only “deaths by COVID-19” and “deaths with COVID-19”, but even deaths “without COVID-19 documented”. Moreover, I had not taken seriously into account weekend reporting delays in death counts.
      Worse, COVID-19 had already started devastating nursing homes in the USA by then, but the nursing home data were mostly unavailable. I could not imagine that despite the Italian and Washington state47 experience, nursing homes were still unprotected. Had I known that nursing homes were even having COVID-19 patients massively transferred to them, I would have escalated my foolish quote several fold.

      There is more to this: since mid-March, I wrote an article alerting that there are two settings where the new virus can be devastating and that we need to protect with draconian measures: nursing homes and hospitals. Over several weeks, I tried unsuccessfully to publish this in three medical journals and in 5 top news venues that I respect. Among top news venues, one invited an op-ed, then turned it down after one week without any feedback. Conversely, The New York Times, offered multiple rounds of feedback over 8 days. Eventually, they rewrote entirely the first half, stated it will appear next day, then said they were sorry. STAT kept it for 5 days and sent extensive, helpful comments. I made extensive revisions, then they rejected it apparently because an expert reviewer told them “no infectious disease expert thinks this way” – paradoxically, I am trained and certified in infectious diseases.

      42-52% of deaths in the US (and as many or more in several European countries) eventually were in nursing homes and related facilities37 and probably another large share were nosocomial, hospital- acquired infections. An editor/reviewer at a top medical journal dismissed the possibility that many hospital staff are infected. Seroprevalence and PCR studies, however, have found very high infection rates in health care workers 48-50 51,52 and in nursing homes.
      Had we dealt with this coronavirus thinking what other widely-circulating coronaviruses do based on medical or infectious disease (not modeling) textbooks (=they cause mostly mild infections, but they can 20,21,53 devastate specifically nursing homes and hospitals), ridiculous.
      Why was my article never accepted? Perhaps editors were influenced by some social media who painted me and my views as rather despicable and/or a product of “conservative ideology” (a stupendously weird classification, given my track record). As I say in my Stanford webpage: “I have no personal social media accounts – I admire people who can outpour their error-free wisdom in them, but I make a lot of errors, I need to revisit my writings multiple times before publishing, and I see no reason to make a fool of myself more frequently than it is sadly unavoidable.” So, here I stand corrected.

      • Nicholas Gruen says:

        Fabulous passage John – thanks. As good an illustration as one could want of the tyranny of the comms folks. Someone with the knowledge, intelligence and humility (proven over the decades) to be put right at the centre of the conversation (and I note his disagreements with others whose perspectives should likewise be central). Instead, he gets stuffed around and bossed about by the thicket of comms know-nothings all keeping themselves busy trying to entertain the troops.

        • Nicholas
          Thought this bit would appeal.
          “ they rejected it apparently because an expert reviewer told them “no infectious disease expert thinks this way” – paradoxically, I am trained and certified in infectious diseases.”

          “ experts live at the cutting edge,of conformity “

          Btw the whole paper is worth a read, unusually clear.

          • The unbelievable repeated tale of infectious people being bundled off to nursing homes in the UK and in the US ,along side the unbelievable ‘insecurity ‘ guards viz the Melbourne quarantine hotels sums my reasons for judging so many of the western worlds expert health systems as, not fit for purpose.

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