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The Current Epidemic Recapitulation

By September 13, 2020September 15th, 2020Commentary

It has been a few weeks since my latest attempt to step back, take a look at everything we think we have learned and know about coronavirus and issue a status report, with a very abbreviated look forward.  I will do the look forward first.  I have no idea what will happen next.  All the research I have read on seasonality and other factors potentially bearing on why the epidemic seems to surge in one place and then another, but not in some, provides no clear guidance or answers.  I don’t think anyone knows.  I think attempts to suppress the virus or even mitigate spread are futile.  It is here to stay, we have to and we will adapt.  We will adapt in large part because, among the realm of potential pathogens, it is not particularly lethal, rarely causing serious disease or death, particularly to the great bulk of the population.  Will it re-emerge in northern temperate latitudes as weather turns cooler?  Is that what is happening in Europe?  Why doesn’t it seem to be happening in the US?  Have some areas seen a combination of enough infections and enough pre-existing immunity to substantially slow any possible transmission?  I don’t think anyone knows.  More important is that we recognize the need to adapt, not make futile attempts to suppress, and that we balance all the costs and harms inflicted by both the virus and our actions in response to it, and act in the interest of the greatest good for the most people, not being obsessed with preventing every possible CV-19 case or death, no matter what the damage to the population’s health and its economic, social and educational well-being.

Otherwise, the status is pretty much as of the last similar post, with the exception of the PCR testing issues.  A lot of unanswered questions remain.  This is an interesting coronavirus strain; nothing really noticeable for almost everyone who is exposed to it, very deadly for a few–the frail elderly, the morbidly obese, some with other serious illnesses.  How is it transmitted–mostly in larger droplets, is there some extensive transmission by smaller aerosol particles, how long does the virus remain viable in such particles, can be picked up off of surfaces on which is has been deposited?  Why is there less transmission outdoors–sunlight, air flow and currents?  We don’t have definitive answers to such basic questions, particularly in regard to the quantification of method of transmission.

How much virus does it take to infect a person, how wide is the range of potential dose, what variables affect the dose needed to start an infection?   How much virus shedding does a person need to do to become infectious, how long do they remain infectious, does infectiousness vary with severity of infection and disease?  The evidence is not conclusive but it appears that asymptomatic and mild infections lead to a lower viral loads and shedding and a shorter period of infectiousness.  The peak of infectiousness appears to coincide with the day of symptom onset, and decline somewhat rapidly after a few days.   Again, important  unresolved issues.

Are we using adequate tests to detect infection and assess the presence or level of infectiousness.  The gold standard would be to culture samples from everyone tested, but that is more expensive, and more importantly, too slow for practical use, when it is crucial to identify truly infectious persons and isolate them and identify others they may have transmitted to.  We know with some certainty now that many labs are calling very marginal results a positive result (according to the New York Times story, up to 90% of all “cases”), and are ignoring fairly well-established research correlating cycle number with culture positivity.  Once again, I am baffled by the ignorance, incompetence or willful disregard of the science by our supposed public health experts.  This is a critical issue for people to understand if they are to have an accurate picture of how widespread the epidemic actually is, and it has direct, very serious ramifications for the individuals receiving a positive result.  Businesses and schools face the threat of shutdown due to the presence of cases, which may well not be cases.  How could public officials not have proactively brought this issue to the attention of the public and addressed it by full transparency about the cycle number being used to call a result positive?  How could they not have insisted on retests of marginal results?  Unfortunately, these failures contribute to conspiratorial thinking.  It leads to an appearance of trying to frighten the public with an excessive number of non-existent cases and justify extreme mitigation actions directed toward a spread that isn’t really occurring.  But why should we be surprised given what we have witnessed from government to date?

We can say with increasing confidence that almost all patients who survive develop a robust and durable adaptive immune response, both B cell (antibodies) and/or T cell ones.  This includes people with symptomatic or mild infections and disease.  Antibody surveys alone will not identify all persons who have been infected nor will many antibody assays be sensitive enough to pick up the presence of antibodies in all previously infected persons.

This epidemic should have shaken up the obvious complacency of the epidemiologists and infectious disease specialists, who were completely incapable of understanding the epidemic other than through the lens of a textbook model, and even then forgot basic first principles.  Human heterogeneity, variability is the key, and understanding and incorporating that variability into our view of the epidemic is the most critical task.  Instead we got simplistic models which largely treated the entire population as homogenous.  God bless Gabriela Gomes and her associated authors for sparking a different approach to modeling, one that incorporates variability along crucial dimensions of susceptibility and infectiousness, resulting in model outputs that look more like what has actually happened.  And where were the immunologists to warn us early on that given the almost universal prevalence of infection with seasonal coronaviruses, people might have pre-existing immune responses to this strain, responses which could be a primary factor in the variability in susceptibility and infectiousness.

What happens at the individual level is collectively reflected in the population level course of the epidemic.  At the individual level, the likelihood of infection, most importantly, of an infection serious enough to make the person infectious, is dependent on a myriad of factors:  the age and sex of the person, health status, population density of where they live or work, number of contacts and who those contacts are with, the strength of their general immune system, the potential of cross-reactive adaptive immunity, the number of virus particles to which a person is exposed, and so on.   When those factors are properly analyzed and fed into modeling formulas, you get a more accurate projection of the shape of the epidemic.

An epidemic slows when the virus no longer easily finds unexposed humans which it can infect and whose cells will be vehicles for replication and transmission to other humans.  That spread can be influenced by a variety of factors and actions, but the most reliable and least costly in many dimensions, is having a sufficient number of people with adaptive immune responses that limit infection, either from being infected by this strain, or because they have the pre-existing cross-reactive response.  Because of heterogeneity in contacts, in dose needed to spark an infection, in immune and health status, and other factors, a smaller fraction of the population than traditionally assumed may need to be infection resistant to cause a substantial slowing of the rate of transmission.  A vaccine can also help create this population-level slowing of transmission.

I am not going to dwell on the disastrous governmental responses to the epidemic to date.  Fed by media hysteria and an obsession with risk aversion, but only to one limited risk, enormous damage has been done.  Our approach to quantifying the epidemic has been irresponsible and also fed the hysteria.  Massive testing with no regard for false positives or marginal results leads to the appearance of large numbers of cases and surges in case growth.  The unprecedented treatment of every death of every person who happened to have, or be suspected of having, some CV-19 in them at some time prior to death, leads to a death number that really is absurdly exaggerated.

There has been much debate about the comparison to flu.  I keep pointing out that if we tested for influenza like we do for CV, if we counted deaths with flu virus like we do those with CV-19 virus, and if we had no vaccine for flu, influenza would account for far more cases and deaths than CV-19 has, and across a much wider range of the population.  Does anyone actually believe that the response was justified by the threat?

 

Join the discussion 13 Comments

  • Chris W says:

    Thanks, Kevin. Well said. Particularly liked the last paragraph. Sadly out governments are still operating under that false premise that 2 million will die in the US. That’s what got this whole thing started and that course of action has been strictly maintained despite the facts to the contrary. This overreaction never, ever would have happened if someone suggested that 200K (Imperial College/Ferguson’s revised figure) would die this year from a flu-like virus. In fact, there would have been no reaction to such a prediction. We need to continue to call our officials out on this.

  • Ganderson says:

    Kevin- at least here in New England College town-land the answer to the question “Does anyone actually believe that the response was justified by the threat?” is an emphatic “yes”; nearly everyone around here is all in on Corona-panic. The academic establishment, from kindergarten up through the universities are all aboard. Nearly everyone in my town is masked- inside, outside, alone, in groups, upstairs, downstairs. Very common to see people walking alone, or riding their bikes alone with masks on. Many school districts’ teachers unions are threatening job actions if forced to have in person classes. Most schools are supposedly opening under a hybrid model- that’ll last until the first kid tests positive – then they’ll go all remote.
    Our local, very prestigious small liberal arts college is operating a bubble- 2 classes back ( and athletes, although there are no fall sports), and the students are to be masked 100% of the time. Students aren’t allowed to leave campus, nor is the general public allowed on campus- sucks for me, as I was accustomed to walking my dog around the grounds. At another, slightly less prestigious college the deal is all remote for the foreseeable future. Similar procedures for the big state university In town.
    It’s flat out nuts here, and I see no signs of the madness going away anytime soon.

  • Ganderson says:

    Oh, and there’s a mandatory mask rule in the downtown area- unless you are sitting in an outdoor cafe- pretty smart virus; it’ll attack me if I’m standing on the sidewalk, but not if I’m sitting 3 feet away in a roped off restaurant area. And, the town has set up a tip line to dime out mask and social distancing scofflaws. Maybe someone will publish a little red book of sayings from Chairman Charlie Baker.

  • SteveD says:

    Cases and deaths for influenza (P&I) are estimated, by extrapolation from testing data. According to the CDC, there are approximately 10-15 million flu infections per year and about 35,000-40,000 deaths (62,000 in 2017) per year. I suppose that would be double without a vaccine. I think infection rate and death rate is higher in many areas of the world (which is where the 0.1 IMR comes from) However, except for specific strains, influenza deaths are usually not from the virus directly but due to pneumonia and other secondary infections. Therefore, seasonal influenza is seldom the sole cause of death.

    It’s very surprising that the the pandemic appears to be so severe in the US compared to elsewhere. If you consider previous pandemics (Asian, Hong Kong, Spanish Flu’s), the US share in world deaths was well below it’s share in world population. According to Worldometer, the US has about 22% of the world’s CoVid cases and 21% of the deaths but only 4% of the world’s population. Those ratios do not make sense.

    • Kevin Roche says:

      I think the apples to apples comparison with flu would be a testing regime where basically everyone is being tested, symptomatic or not. We would clearly find huge numbers of people with influenza virus if we used the same test approach and test measures. And then if we treated every patient who dies with a positive influenza test as an influenza death, that would also be a very large number. CV-19 deaths are also rarely directly from CV, the most common chain, having inspected a large number of actual death certificates, is CV-19 to pneumonia to ARDS. And influenza undoubtedly has a much higher impact on younger adults and children than CV-19 does. I don’t think the pandemic is more severe in the US than elsewhere. Looking at per capita death rates, and ignoring different regimes for determining a CV-19 death, we are right in the middle of Europe. Most of the world’s population is in Asia and Africa. Those areas have far younger populations, so you would need to age adjust populations at a minimum to make a comparison. Cases are impossible to compare, look at Worldometers, the US does more testing per capita than any other country, so why wouldn’t we appear to have a high number of cases. Look at Japan’s testing rate, that undoubtedly is why they have so few cases. So case comparisons are pretty meaningless. hospitalizations and deaths, properly adjusted for age, gender, and health status, are more appropriate measures of epidemic experience.

  • Alex says:

    “According to Worldometer, the US has about 22% of the world’s CoVid cases and 21% of the deaths but only 4% of the world’s population. Those ratios do not make sense.”

    They don’t make sense because it’s a meaningless statistic.

    Cheers.

  • SteveD says:

    The CDC counts almost 10,000 cases where CoVid-19 is the sole cause of death. According to them, there were no contributing co-morbidities or additional pathogens. Right from the beginning I realized that Covid-19 is a cold virus but can also directly cause pneumonia.

    The broader estimate for influenza from the CDC in the US is 10-45 million cases including a very large number of asymptomatic cases (65-85%). Although the CoVid and influenzas deaths are determined by different means, the general definition is the same. (if it’s a contributing, primary or sole cause of death)

    https://www.cdc.gov/flu/about/burden/index.html

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586318/#:~:text=Influenza%20virus%20infections%20lead%20to,of%20that%20infection%20(2).

    If we tested everyone for influenza over the course of a bad flu season, would we find a lot more than 45 million cases? Maybe but it seems a stretch.

    It looks like Europe has about 13% of the world’s cases based on the same data. I looked at the US/Europe/World comparison a couple months ago before the US overtook the rest of the world in testing and ratios were similar. So I am not convinced that testing rate per se explains most of the difference. Whether your positivity rate goes up or down depends whether you predominantly test positives or negatives. In my opinion the difference is more likely explained by the methodology rather than the number of tests. However, I don’t have the data I need to prove that yet. It seems suspiciously absent.

    “Those areas have far younger populations, so you would need to age adjust populations at a minimum to make a comparison.”

    This doesn’t explain the comparison I made to the earlier pandemics of 1958 and 1969, though. They also predominantly hit older populations (although 1919 did not).

  • “An epidemic slows when the virus no longer easily finds unexposed humans…” Yes, true, but it also slows when the hosts it finds are “resilient”. No one talks about resilience even though there is an abundance of science strongly suggesting that specific micronutrient deficiencies create far greater levels of morbidity. Vitamins D, C, and A along with minerals zinc and selenium are critical for healthy immune function particularly with respect to respiratory viruses. Being significantly deficient in one or more of these will create greater morbidity. Being optimally nourished with these will compress morbidity into a nuisance illness and little more. Also melatonin is critical in mediating the effects of respiratory viruses in the pulmonary membranes. Melatonin is usually highest in children that may be part of the explanation for why their morbidity is so minimal. Our medical leaders do not talk about any of these factors all of which are inexpensive and easily acquired. This in my opinion is one of the greatest crimes of the pandemic. Simple nutritional supplementation would create very resilient hosts across the full continuum of the community. Herd immunity would develop with minimal morbidity and mortality.

  • SteveD says:

    My original post for some reason did not save yesterday so here is take 2. I wonder if it timed out the first time? Anyway…

    “And then if we treated every patient who dies with a positive influenza test as an influenza death, that would also be a very large number.”
    The number of influenza deaths per year according to the CDC is 9-45 million. The number of Covid-19 cases is presently about 6.5 million, which is well below that range. 65-85% of these influenza cases are asymptomatic and therefore likely marginal. It seems more likely that we are undercounting CoVid cases and therefore deaths in comparison with influenza.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586318/#:~:text=Influenza%20virus%20infections%20lead%20to,of%20that%20infection%20(2).
    https://www.cdc.gov/flu/about/burden/index.html
    The CDC ‘definition’ of an influenza death and a CoVid death is identical, although how they determine the number of deaths is different (direct count vs. estimate). In both cases a death counts if the virus is thought by the physician to be a contributing, primary, or sole cause of death. If as you say they are counting everyone who dies with a positive test, then they are not doing to according to guidelines. According to the CDC just short of 10,000 CoVid deaths have no other contributing cause. They were caused solely by the virus by cytokinin storm and/or pneumonia.

    “Melatonin is usually highest in children that may be part of the explanation for why their morbidity is so minimal.”

    They also don’t talk much about obesity which I believe may be the largest contributing cause to death.

    One of the most curious aspects of Covid-19 is that it barely affects newborns who are particularly susceptible to other respiratory viruses (viral pneumonia and influenza). In fact, those viruses are the leading cause of death for people between birth and one year. So at least for those under one year, something we do not understand is going on. BTW, I agree, nutritional supplements, zinc, walking outside during the day, exercise etc. are all good ideas and they should be discussed. I am sure they do a lot more than many of their ideas (e.g. masks).

    But the fact that young people and especially infants are not much affected by this virus is an incredible stroke of luck. If I was told we had to have a pandemic but I could chose one mitigating factor, I would ask for it to be harmless to children. So what do we do to take advantage of this fantastic good fortune? Close all the schools, of course. Bah.

  • SteveD says:

    “And then if we treated every patient who dies with a positive influenza test as an influenza death, that would also be a very large number.”
    The number of influenza deaths per year according to the CDC is 9-45 million. The number of Covid-19 cases is presently about 6.5 million, which is well below that range. 65-85% of these influenza cases are asymptomatic and therefore likely marginal. It seems more likely that we are undercounting CoVid cases and therefore deaths in comparison with influenza.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586318/#:~:text=Influenza%20virus%20infections%20lead%20to,of%20that%20infection%20(2).
    https://www.cdc.gov/flu/about/burden/index.html
    The CDC ‘definition’ of an influenza death and a CoVid death is identical, although how they determine the number of deaths is different (direct count vs. estimate). In both cases a death counts if the virus is thought by the physician to be a contributing, primary, or sole cause of death. If as you say they are counting everyone who dies with a positive test, then they are not doing what they should, according to guidelines. According to the CDC just short of 10,000 CoVid deaths have no other contributing cause. They were caused solely by the virus by cytokinin storm and/or pneumonia.
    “Melatonin is usually highest in children that may be part of the explanation for why their morbidity is so minimal.”
    They also don’t talk much about obesity which I believe may be the largest contributing cause to death.
    One of the most curious aspects of Covid-19 is that it barely affects newborns who are particularly susceptible to other respiratory viruses (viral pneumonia and influenza). In fact, those viruses are the leading cause of death for people between birth and one year. So at least for those under one year, something we do not understand is going on. BTW, I agree, nutritional supplements, zinc, walking outside during the day, exercise etc. are all good ideas and they should be discussed. I am sure they do a lot more than many of their ideas (e.g. masks).
    But the fact that young people and especially infants are not much affected by this virus is an incredible stroke of luck. If I were told we had to have a pandemic, but I could choose one mitigating factor, I would ask for it to be harmless to children. So, what do we do to take advantage of this fantastic good fortune? Close all the schools, of course. Bah.

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