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Thread: Disease and pandemics thread (because it's science)

  1. #2551
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    So I guess that explains the 21 vs 28 days between shots for the Pfizer and Moderna vaccines. They probably tried several intervals during phase one trials and those looked to give the best response.
    I may have many faults, but being wrong ain't one of them. - Jimmy Hoffa

  2. #2552
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    I thought this was interesting
    Chemical & Engineering News

    Plitidepsin, a natural product made by sea squirts and developed by PharmaMar as the anticancer drug Aplidin, could be used as a COVID-19 antiviral. Researchers found that the compound is over 27 times as potent as the antiviral remdesivir (marketed as Veklury by Gilead Sciences) at killing SARS-CoV-2, the virus that causes COVID-19, in cells. It also prevented SARS-CoV-2 from replicating in the lungs of mice (Science 2021, DOI: 10.1126/science.abf4058).
    Here is the journal article

    Abstract:
    SARS-CoV-2 viral proteins interact with the eukaryotic translation machinery and inhibitors of translation have potent antiviral effects. Here we report that the drug plitidepsin (aplidin), which has limited clinical approval, possesses antiviral activity (IC90 = 0.88 nM) 27.5-fold more potent than remdesivir against SARS-CoV-2 in vitro, with limited toxicity in cell culture. Through the use of a drug resistant mutant, we show that the antiviral activity of plitidepsin against SARS-CoV-2 is mediated through inhibition of the known target eEF1A. We demonstrate the in vivo efficacy of plitidepsin treatment in two mouse models of SARS-CoV-2 infection with a reduction of viral replication in the lungs by two orders of magnitude using prophylactic treatment. Our results indicate that plitidepsin is a promising therapeutic candidate for COVID-19.
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  3. #2553
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    Sounds intriguing. One positive thing that could come from this pandemic is that a lot of people are taking a close look at various drugs, and we might learn some new things about compounds that arenít so well understood now.


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  4. #2554
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    The NY Times, in partnership with PHICOR, just published a tool for assessing herd immunity in the US and looking at several variables that play a role; vaccine rollout, easing of precautions, and emerging variants. It's certainly complicated and also interesting (in a scary way) that some models increase herd immunity but at the expense of incremental deaths.

    https://www.nytimes.com/interactive/...gtype=Homepage

  5. #2555
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    We're now far enough into the Covid vaccination roll-out that we're beginning to see real-world vaccine effectiveness data. (Effectiveness is almost always lower than efficacy, as measured by clinical trials, because not everyone in a population receives the vaccine.)
    The EAVE-II national monitoring project in Scotland has just released some early pre-print results from the first tranches vaccinated, who are now a month past their first dose of either Oxford or Pfizer vaccine. They're seeing an 81% reduction in hospitalization risk in the over-80s.

    Early days, and see the Discussion in the paper for some cautions, but it's difficult to overstate how impressive that result is, if it holds good. That age-group is notoriously poor at mounting an effective immune response, and notoriously sensitive to minimal physiological disturbance, so this is a dramatic effect. But they're also more vaccine-compliant--by the start of February we had vaccinated 93% of over-80s living in the community in Scotland, and more than 99% of care-home residents.
    There's going to be a trade-off as we descend into younger age-groups--better immune responses, more robust physiology, but also reduced vaccine uptake.

    EAVE-II should be able to observe all this as it evolves--we're fortunate to have a very joined-up health-care system in Scotland, so it's possible to monitor pretty much the entire population as a cohort.

    Grant Hutchison

  6. #2556
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    Looks like we lucked out on the COVID-19 vaccines. Early on there was a lot of question about whether a reasonably effective vaccine could be produced, and it seems between the virus and the technology they managed to do really well. I wouldnít want to think what it would be like if they couldnít get a good vaccine and if the body had trouble mounting a long term natural immune response.

    Iím also happy and impressed that positivity rates are improving in many places. Iím wondering if giving the vaccines to the older population is having a bigger impact than you might expect just from counting the number vaccinated?

    California rates have been really dropping as well as hospitalizations. All over the state, but if I am reading the numbers right, my county may be able to shift to a more permissive tier soon. It seems like during the holidays a lot of people got together when they shouldnít have and the state paid for that, but maybe more wised up since then.

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  7. #2557
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    It'll be interesting to see what happens in the European Union now, given that these early results from Scotland show the Oxford/AstraZeneca vaccine performing, if anything, more effectively than Pfizer overall (but with broad confidence limits), and equally strongly effective in the over-80s.
    Recently, there was a weird meme generated by a German newspaper that the Oxford vaccine was only 6% effective in over-65s, and the French President cheerfully announced that it was "quasi-ineffective" in that age-group. German health authorities have indeed been restricting its use to the under-65s, but because of lack of robust data from clinical trials (the numbers over 65 were relatively low) rather than any clinical evidence that the efficacy was poor. And the laboratory data (measuring antibody response) has always shown a good immune response in older people, leading WHO to have confidence that it should be used in all age groups.
    But now the EU seems to have saddled itself with a degree of "Oxford hesitancy" as a result of misinformation and misunderstanding. See, for instance, this recent article in Der Speigel (international edition) about "the vaccine no-one wants", with healthcare professionals refusing vaccination with the Oxford/AstraZeneca vaccine.

    Grant Hutchison

  8. #2558
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    Quote Originally Posted by Roger E. Moore View Post
    I'm going to hate it when COVID-19 shows up again this fall, alongside the flu, and we go through this all over again.

    What are the chances of comorbidity, I wonder.
    Pretty much zero. Which also happens to be the number of flu cases.

  9. #2559
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    We now know that coinfection with Covid and flu doubles your risk of dying, compared to Covid alone, but that there also appears to be a protective effect, in that having flu reduces your risk of Covid by almost a half.
    So for many people, that's double a small risk (I quoted a small case series back in April, when Roger E. Moore posted his question, and everyone survived). But for some people that's pretty significant.
    As you suggest, this year's flu season has fizzled, for obvious reasons, and that may have long-term consequences.

    Grant Hutchison

  10. #2560
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    Quote Originally Posted by grant hutchison View Post
    As you suggest, this year's flu season has fizzled, for obvious reasons, and that may have long-term consequences.
    Sidenote, from the article:
    Despite humanity’s long history with colds and flu, the viruses that cause them still hold many mysteries.
    Bold mine.

    To be fair, we've really only been solving the mysteries of viruses since 1898, not all of human history. (We can quibble about the date, but whatever.)

    I for one am extremely glad we live in the age of scientific medicine. I would be long dead if we didn't have that vital knowledge, much as some fools may try to deny it these days. Imagine life if modern travel and transport existed, but the germ theory of medicine had never been discovered! Disease and pandemics, indeed.
    "I'm planning to live forever. So far, that's working perfectly." Steven Wright

  11. #2561
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    My wife and were just now scheduled to get our shot #1 on Weds and shot #2 on April 1st (no fooling). I'm assuming that we're getting the Moderna shot (a 4 week wait). I have read that the Pfizer vaccine requires a dilution procedure before administering but the Moderna shot does not.

  12. #2562
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    Quote Originally Posted by grant hutchison View Post
    As you suggest, this year's flu season has fizzled, for obvious reasons, and that may have long-term consequences.

    Grant Hutchison
    For far too many people, unfortunately, the obvious reason is that flu deaths are being falsely reported as Covid. Along with all other deaths because it's all a hoax. The capacity of humans to believe insane conspiracy theories just continues to amaze.
    Cum catapultae proscriptae erunt tum soli proscript catapultas habebunt.

  13. #2563
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    Yes, lies, damn lies, and statistics. But in this case I suspect it's because most people are math-challenged. among other causes.

    The content below is a bit dated but the point remains; deaths in 2020 outstripped what was expected/predicted. Click on the link for charts.

    https://usafacts.org/articles/prelim...virus-age-flu/

    Preliminary US death statistics show over 3.1 million total deaths in 2020óat least 12% more deaths than in 2019

    While death certificates from the last eight weeks of 2020 and more are still being processed, over 334,000 more people died in 2020 than in all of 2019.

    From 1980 to 2019, between eight and nine people per 1,000 have died each year in the United States. In 2019, the most recent year with official death estimates, 2,854,838 Americans died, and 3,747,540 were born. That means that 8.7 people died per 1,000 that year ó up from a low of 7.9 deaths per 1,000 people in 2009.

    Due to lag time in reporting, official data on 2020 deaths will likely not be released until late 2021 or early 2022. However, preliminary weekly data can provide estimates of how the pandemic affected deaths in the US this year.

    How many people have died so far in 2020?

    So far, more than 350,000 Americans have died of COVID-19. According to preliminary weekly data from the Centers for Disease Control and Prevention (CDC) (as of January 6, 2021), 3,187,086 people died from all causes between January 1 and December 26, 2020. While this data is preliminary and is incomplete for at least the last eight weeks of reported data, it provides for useful context.

    According to the same estimates, 2,852,609 people died in 2019, meaning at least 334,000 more people have died so far in 2020 than 2019, despite missing or incomplete data for October through December. Using the recent estimate of the 2020 population from the Census Bureau, the death rate so far in 2020 would be 9.7 deaths per 1,000, the highest death rate since 1949. However, the recent population estimate does not incorporate the results of the 2020 Census, which should improve the accuracy of the estimate.

    For context, the most recent estimates from the Census Bureau, which are from 2017, projected that there would be 2.75 million deaths in 2020, accounting for an aging population. The Census Bureau did not expect the nation to reach 3.1 million deaths until 2029 or 2030.

  14. #2564
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    Disease and pandemics thread (because it's science)

    According to the article below, New Orleans deaths jumped by about 30% last year. COVID was the biggest contributor, but homicide and accidental categories also jumped. I wonder how many of those were indirectly related.

    https://www.nola.com/news/article_40...4fa264c23.html
    I may have many faults, but being wrong ain't one of them. - Jimmy Hoffa

  15. #2565
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    I have a quick question, based on a conversation I had earlier today. In Japan, as in many other places, a lot of the cases have been clusters in nursing homes and hospitals. I was a bit surprised that on the news, they said that about 80% of the cases in Tokyo have been in those settings. So the question is why. Part of the reason may be that there is poor ventilation and that people are close together, but I guess a major reason is simply that the people in those settings have compromised immune systems, and that in a normal setting, say a train or the workplace, people will not get infected simply because their immune system defeats the virus before it takes hold, while in nursing homes the people are not able to fight it as well. This also explains I think why there are also outbreaks of influenza in nursing homes and the like.
    As above, so below

  16. #2566
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    I believe it is primarily due to a large number of older people in those crowded settings which have a less effective immune response even if healthy - not necessarily compromised, just dealing with the natural effects of aging on immunity, though it can be compromised too if they are taking drugs or having treatments that do that. From what Iíve read, ventilation isnít as important as the crowding, since people are much more likely to come in contact in those conditions. By far, the greatest number of hospitalizations and deaths have been with the oldest people. Thatís why care homes have been something of a nightmare during the pandemic. By the way, I havenít looked into it, but I expect memory care facilities are the worst. Many of the patients wouldnít understand they needed to be careful, they are usually quite old, and family wouldnít be able to interact directly with them, so they probably have been deteriorating mentally faster than they would otherwise. In a way, Iím happy my mother didnít live long enough to go through the pandemic.

    "The problem with quotes on the Internet is that it is hard to verify their authenticity." ó Abraham Lincoln

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  17. #2567
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    Quote Originally Posted by Van Rijn View Post
    I believe it is primarily due to a large number of older people in those crowded settings which have a less effective immune response even if healthy - not necessarily compromised, just dealing with the natural effects of aging on immunity, though it can be compromised too if they are taking drugs or having treatments that do that. From what I’ve read, ventilation isn’t as important as the crowding, since people are much more likely to come in contact in those conditions. By far, the greatest number of hospitalizations and deaths have been with the oldest people. That’s why care homes have been something of a nightmare during the pandemic. By the way, I haven’t looked into it, but I expect memory care facilities are the worst. Many of the patients wouldn’t understand they needed to be careful, they are usually quite old, and family wouldn’t be able to interact directly with them, so they probably have been deteriorating mentally faster than they would otherwise. In a way, I’m happy my mother didn’t live long enough to go through the pandemic.
    Just to be clear, by "compromised" I really just meant "less effective." Maybe it is too strong a term. And in that sense, I completely understand why the death rate is higher. The interest more is in how it gets into those settings in the first place. Here, as in many other places, visitations have been restricted. So is it just that one medical care worker gets infected and brings it in, and then it passes among the people? I'm guessing that's basically the answer. In a workplace, one person might have the virus, but it doesn't spread either because there is less contact or the people are able to fend it off, while in a nursing home, if one worker comes in with the virus, it just spreads?
    As above, so below

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    Quote Originally Posted by Jens View Post
    Just to be clear, by "compromised" I really just meant "less effective." Maybe it is too strong a term.
    Of course, I don’t claim expertise here, I just remember reading an article where a doctor made a distinction between gross compromise of large parts of the immune system caused by immunosuppressive drugs, radiation, some diseases, and certain conditions versus effects of natural aging where the immune system was still largely functional but not working as effectively as that of a younger person.

    And in that sense, I completely understand why the death rate is higher. The interest more is in how it gets into those settings in the first place. Here, as in many other places, visitations have been restricted. So is it just that one medical care worker gets infected and brings it in, and then it passes among the people? I'm guessing that's basically the answer. In a workplace, one person might have the virus, but it doesn't spread either because there is less contact or the people are able to fend it off, while in a nursing home, if one worker comes in with the virus, it just spreads?
    I don’t know for sure, but I would guess health workers and new patients. We’ve seen other cases where efforts have been made to keep the disease out but it slipped in. For instance, there was an attempt at an upscale ocean cruise where everyone was tested before allowed onboard but it got past them and spread. The cruise was quickly aborted. It only takes one person, and it isn’t always obvious when someone is infectious and tests don’t always work. Here you would have staff going home so there would be many more opportunities for infection, though they would likely be taking more care attempting not to infect patients than cruise ship staff around passengers. But there would be crowded conditions in both cases.

    "The problem with quotes on the Internet is that it is hard to verify their authenticity." ó Abraham Lincoln

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  19. #2569
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    Quote Originally Posted by Jens View Post
    I have a quick question, based on a conversation I had earlier today. In Japan, as in many other places, a lot of the cases have been clusters in nursing homes and hospitals. I was a bit surprised that on the news, they said that about 80% of the cases in Tokyo have been in those settings. So the question is why. Part of the reason may be that there is poor ventilation and that people are close together, but I guess a major reason is simply that the people in those settings have compromised immune systems, and that in a normal setting, say a train or the workplace, people will not get infected simply because their immune system defeats the virus before it takes hold, while in nursing homes the people are not able to fight it as well. This also explains I think why there are also outbreaks of influenza in nursing homes and the like.
    It is presumably a subject for research as to why this virus seems to afflict proportionally with age, many viruses do not. Maybe the generalised immune defences decline linearly with age and this virus is thus easily beaten (on the whole) by younger people. That decline is indeed an irritating property for those of us past middle age because we have little control over it. Since this is a respiratory virus the odds are you catch it by breathing and once infected, you broadcast it by breathing too. So elderly people in nursing homes with regular meetings with staff must be very vulnerable and probably receive regular doses of virions increasing their chances of catching it. Ventilation will change the dose and as Grant explained to my much earlier question, there must be a stochastic element, you only need one virus inside one cell in theory and you are infected. To stay uninfected your general immune system defeats every single particle. The bigger the dose and the frequency thereof, the more your chances grow of being infected. Many other nasty viruses infect and kill children, we hope this one is beaten before it evolves that ability.
    sicut vis videre esto
    When we realize that patterns don't exist in the universe, they are a template that we hold to the universe to make sense of it, it all makes a lot more sense.
    Originally Posted by Ken G

  20. #2570
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    Quote Originally Posted by Jens View Post
    I have a quick question, based on a conversation I had earlier today. In Japan, as in many other places, a lot of the cases have been clusters in nursing homes and hospitals. I was a bit surprised that on the news, they said that about 80% of the cases in Tokyo have been in those settings.
    We should also wonder why only 20% of deaths in Japan occurred outside care-homes, since that's a lot lower proportion than in Europe, where community-acquired infection accounts for most deaths, with care home deaths sitting somewhere between quarter and half of the total. I've seen many hypotheses about the low overall Covid death rate in Japan, but the last time I looked there didn't seem to be a robust front-runner.
    Anyway, people have already spoken about reduced immunity and a confined indoor environment. But the primary issue here is frailty, which is is a progressive state of diminishing physiological reserve which makes it harder and harder for a person to cope with activities of daily living, and less and less able to recover from disruptions to their physiological equilibrium. So something that might cause a less frail person to feel unwell for a couple of days can tip a frail person over the edge into a spiral of physiological decline culminating in death. There are formal ways of assessing it, but you can get a feel for it from Dalhousie's Clinical Frailty Scale.
    So care home residents are generally severely frail, and are at high risk of death if their physiology is even slightly disrupted. So we see deaths in care homes from flu, we see deaths from norovirus, we see deaths from C. difficile--pretty much any disease that is readily transmitted by droplets, contact or surfaces. There's nothing exceptional about Covid in this regard, except that it has a very high prevalence at present and has a degree of asymptomatic or presymptomatic spread, so that it's difficult to keep out of care homes.

    Grant Hutchison

  21. #2571
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    It may be a tangent, but frailty reminds me of bones for which I devised a ex vitro test in my final year. I was testing the Tibia. We were supplied small samples of human bone from cadavers with age and sex details. I don't think you could do that now but it was legal then.

    The test was aimed at better technology for plating broken bones, especially in ski accidents. Sheep were also involved . Anyway the point is the elastic modulus and ultimate tensile values were drastically reduced in samples from older people. The elasticity by half, quoting from memory, and the UTS by five times.

    Calcification is dynamic and if you avoid impacts, your bones decalcify. I imagine, speculatively , that your immune system also winds down if not regularly challenged. After all it consumes energy, and our bodies try to conserve energy. Other studies in bones at that time (in particular Evans and Lebow, USA) showed reduction of calcification as crystal apatite in just one day of bedrest! Sitting all day in a chair is just as bad.

    If bones are a proxy for immune cells, then inactivity is bad for you.! On the positive side, one good impact a day was thought to maintain calcium level. Equivalent to jumping off a chair onto a hard surface. I do wonder therefore if social isolation might detune your immune system, it would be plausible.
    sicut vis videre esto
    When we realize that patterns don't exist in the universe, they are a template that we hold to the universe to make sense of it, it all makes a lot more sense.
    Originally Posted by Ken G

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    Quote Originally Posted by profloater View Post
    It may be a tangent, but frailty reminds me of bones for which I devised a ex vitro test in my final year. I was testing the Tibia. We were supplied small samples of human bone from cadavers with age and sex details. I don't think you could do that now but it was legal then.

    The test was aimed at better technology for plating broken bones, especially in ski accidents. Sheep were also involved . Anyway the point is the elastic modulus and ultimate tensile values were drastically reduced in samples from older people. The elasticity by half, quoting from memory, and the UTS by five times.

    Calcification is dynamic and if you avoid impacts, your bones decalcify. I imagine, speculatively , that your immune system also winds down if not regularly challenged. After all it consumes energy, and our bodies try to conserve energy. Other studies in bones at that time (in particular Evans and Lebow, USA) showed reduction of calcification as crystal apatite in just one day of bedrest! Sitting all day in a chair is just as bad.

    If bones are a proxy for immune cells, then inactivity is bad for you.! On the positive side, one good impact a day was thought to maintain calcium level. Equivalent to jumping off a chair onto a hard surface. I do wonder therefore if social isolation might detune your immune system, it would be plausible.
    T cell immunity gets really bad with aging. The thymus turns to fat.
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    I was reading a perspective a month ago in Science, "Sex differences in immune responses". The precise age mentioned in these paragraphs struck me:

    Quote Originally Posted by Science Magazine Vol. 371, Issue 6527, pp. 347-348 Issue of 2021-01-22
    Sex has a major impact on immune cell transcriptomes; immune cells or even the immune system are differentially affected by aging, depending on sex. Aging induces a decline in the proportion of naÔve T cells that is more prominent in males, and B cells decline after age 65 only in males (10). Males have abrupt and drastic changes in the epigenetic landscape of their immune cells between ages 62 and 64, and subsequently males exhibit an accelerated immunosenescence phenotype that is characterized by enhanced innate proinflammatory gene expression and lower gene expression related to adaptive immunity, which could potentially predispose older males to hyperinflammation and poor adaptive immune responses.

    By contrast, major changes in the epigenetic landscape of immune cells occur in females 5 to 6 years later than in males, with this gap largely corresponding to the life span differences between sexes (10). ...
    Maybe it doesn't make a huge difference as vaccines become more readily available, but could this sort of detailed understanding play a role in setting the vaccination schedule?

  24. #2574
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    Quote Originally Posted by grant hutchison View Post
    We should also wonder why only 20% of deaths in Japan occurred outside care-homes, since that's a lot lower proportion than in Europe, where community-acquired infection accounts for most deaths, with care home deaths sitting somewhere between quarter and half of the total.
    The 20% figure was for Tokyo so other areas, say with more ski resorts or other relatively enclosed spaces where people gather, will tend to expand those figures.

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    Quote Originally Posted by LaurieAG View Post
    The 20% figure was for Tokyo so other areas, say with more ski resorts or other relatively enclosed spaces where people gather, will tend to expand those figures.
    Yes, I misread Jens's post in two different ways, and kicked off about care home deaths, rather than nursing home and hospital cases. The figure for the whole of Japan seems to be that "only" 14% of Covid deaths have occurred in nursing homes, according to a recent JAMA paper. "Nursing home" and "care home" mean different things in the UK, but the quoted "nursing home" figure of 35% for the USA in that paper compares with the 40% figure reported for "care sector" (nursing+care homes) deaths in the UK after the first pandemic wave. There's the potential (as with so many international health comparisons) that we're not comparing like with like, however.
    But if the figure for nursing home deaths is only 14% in Japan overall, in the frailest population, then the figure of 80% of cases in Tokyo occurring in "nursing homes and hospitals" seems to imply that disease transmission is occuring damn near exclusively in hospitals. That could be compared to a figure of something like 1/3 or 1/4 of cases in England notoriously acquired in hospital last spring, when testing was limited, understanding poor and PPE scarce. That's a real puzzle.

    Grant Hutchison

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    Did Japan, or within Tokyo, shut down swiftly the visiting to “care” homes, as other countries, with benefit of hindsight, might have done, recognising the vulnerability, as soon as the Chinese announced the new virus? Some countries, as is well known, did shut down comprehensively and have seen fewer cases.
    sicut vis videre esto
    When we realize that patterns don't exist in the universe, they are a template that we hold to the universe to make sense of it, it all makes a lot more sense.
    Originally Posted by Ken G

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    Quote Originally Posted by profloater View Post
    Did Japan, or within Tokyo, shut down swiftly the visiting to “care” homes, as other countries, with benefit of hindsight, might have done, recognising the vulnerability, as soon as the Chinese announced the new virus? Some countries, as is well known, did shut down comprehensively and have seen fewer cases.
    From the JAMA paper I linked to:
    Swift government action in Japan also contributed to the low number of COVID-19 cases among residents of nursing homes. On January 31, 2020, when only 12 cases were reported in the country, the Japanese government initially informed LTC agencies about how to respond to COVID-19. On February 24, the government ordered LTC facilities to be locked down.
    Grant Hutchison

  28. #2578
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    Quote Originally Posted by grant hutchison View Post
    From the JAMA paper I linked to:

    Grant Hutchison
    Thank you, I did not spot the link.
    sicut vis videre esto
    When we realize that patterns don't exist in the universe, they are a template that we hold to the universe to make sense of it, it all makes a lot more sense.
    Originally Posted by Ken G

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    Quote Originally Posted by profloater View Post
    Thank you, I did not spot the link.
    That said, my mother's care home here in the UK locked down only two weeks after Japan's did, and that's pretty much precisely the time difference between the first identified case in Japan (16 Jan) and the UK (31 Jan). At that point in the epidemic trajectory in the UK care homes were still making their own infection-control decisions, however.

    Grant Hutchison

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    I was reading about the J&J COVID vaccine, and see that it uses an adenovirus vector. Is this virus a common one, and might some peopleís immune system recognize it from past exposure and destroy it before it can do its work?
    I may have many faults, but being wrong ain't one of them. - Jimmy Hoffa

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