A few C19 Predictions (from 2020-05-05)

Tuesday, May 5, 2020 

UPDATE: Sept 2022

The introduction of the first successful vaccine was much faster than I anticipated, the first shots going into arms Dec 14, 2020, just 7 months after I wrote this – a lot shorter than the 18 months generally predicted in early 2020.  This was due to the emergency use authorization given to the mRNA vaccines which were already much further along than I was aware based on a decade’s research on SARS.  That was great and unexpected news.   Otherwise things have generally played out as predicted from relatively short immunity (we should all be getting our 5th shot around now) and almost certainly contributing to the global instability we’re experiencing globally.


The most reasonable way to plan for the future is to project from the past.  Anything else is magical thinking.

There’s no vaccine, there’s no rational reason to believe one will be generally available in <18 months even if any of the current candidates works perfectly, there’s plenty of reasons to believe there will not be one in our lifetimes, by far the most likely outcome based on the lack of success of all vaccine efforts to date for corona family viruses, which have included many promising candidates that made it into human trials only to prove ineffectual.  Sure, maybe we get lucky, but so too we might all win the lottery.  The history of corona virus vaccine development projects forward to no vaccine for a long, long time if ever.  Anyone confidently saying “when a vaccine is available” rather than “if a vaccine is available” is thinking magically.  “When we figure out warp drive, we can visit the stars!”  Further, if immunity isn’t long lasting, so too will vaccines be short-lived, not that getting a shot every 3 years or even every 3 months isn’t vastly better than getting sick with a potentially fatal disease that often.  It is, and even a short-lived vaccine will at least make life much easier for those with access to it.

Immunity/Vaccine No Vaccine Vaccine works
Short Immunity Average human lifespan drops substantially, wealthy countries benefit from pharmaceutical interventions, travel never recovers. Wealthy populations live normally but with regular boosters, poor die young(er)
Long Immunity Poor/uncontrolled populations have economic advantage due to rapid herd immunity. Starting 18 months after successful P3 trials, 1-2 years to wealthy country immunity. In 40-50 years C19 may be completely eradicated.

This means that, while the possibility of a vaccine as a path to immunity without getting sick is possible, it isn’t probable.  It is not rational to isolate with the expectation of escaping a C19 infection, rather isolation delays the (probably) inevitable infection almost everyone is going to get, isolation should be considered a purely temporary strategic pause that is squandered if not used to best advantage.

There’s no novel or specific pharmaceutical intervention, though some medications show promise of mitigating mortality.  It does appear that good old-fashioned high-quality medical care in not overwhelmed facilities achieves an amazing reduction in CFR – from 12-14% all the way down to about 0.6% and possibly even lower. Sure, that’s probably at least a big chunk of sampling bias, but not all and that’s pretty awesome.  It is normal that treatment improves with sufficient attention and resources and also quite reasonable to expect that some combination of medications will help mitigate the impact of the disease, perhaps systemically (for everyone who gets it), but almost certainly for mitigating certain problematic conditions.  Some improvement is inevitable given the wide range of outcomes as good data accumulates: there are reasons why there is so much difference in outcome, we will figure some of those out.  Science: it takes time, but it is happening.

This means is that delaying getting sick by quarantine or other measures has two values – first and most importantly it reduces the risk of overloading regional medical response capabilities which seems to, and reasonably would, correlate with much better patient outcomes.  It also means it isn’t absurd to delay as long as possible getting sick if you fall into one of the categories currently indicated as being particularly at risk for a bad outcome as it isn’t unreasonable to believe the protocols for achieving a successful outcome will improve in time, even absent a miracle drug.

All solutions are hyped, none are promising: by now people have to be getting jaded reading breathless headlines or absurdly emphatic pre-pub papers about this team or that discovering some cure or being on the verge of a vaccine.  Every researcher is working late hoping to be the hero that saves humanity, and we’re all desperate to find that hero, but so far, there’s no easy solution.  We’re all inclined to fall into a confirmation bias trap finding some iconoclastic researcher claiming promising results from a process that confirms one’s own pet theory: that should always be a red flag.  This is a long slog: years, perhaps many.

Humanity has to prepared to live with this from now on, even while hoping for a vaccine or cure. It isn’t something we can hide inside from until it gets bored and goes away.  It isn’t some planet-to-planet salesman who’s going to give up if we don’t come to the door and move on.  As a species, we have to find some enduring accommodation to a disease that is highly contagious, is transmissible in individuals with no symptoms, and has a problematically high mortality rate.  We are not sure yet whether we will develop lasting immunity and push it into containable corners of the population eventually or not, but even the least controlled areas will take many months if not years to develop R<1.0 herd immunity necessary to ensure a single infectious person doesn’t trigger an exponentiation surge in the sick and dying, and they will do so at high cost.  The regions that practice the most effective interventions delay achieving herd immunity, possibly indefinitely if immunity isn’t long lasting.

Universal quarantine is not sustainable: stay at home orders are intrinsically temporary, whether the people issuing them understand this or not.  How long they will last depends on submission level of the population, “herd economics” – that is the economic capacity of a sufficient majority to maintain law and order, and the interventions of the government or community to mitigate the consequences.  “Economic” consequences are just an abstraction of hunger, homelessness, access to medical care, funeral services, heat, air conditioning, light, and refrigeration; the poorest regions are falling first to the economic (and medical) consequences of quarantine: in Kenya more people have been executed for violating quarantine than have died of C19. There are riots in India and Lebanon, massive protests in the US.  This can not last, it is an emergency temporary hold to buy time to design and implement a sustainable mitigation or it is an astonishingly tragic waste of the limited resources humanity had in the face of a calamity that will merely delay the inevitable and result in a far, far worse systemic outcome than doing nothing would have.  If quarantine collapses without a clear plan, it does so at the exhaustion of capital resources, both individual and governmental, and drops a globally impoverished world, still lacking sufficient immunity, into a now globally distributed pandemic that we still have almost no resistance to and have far less resources to fight.

Lifting quarantine just because the “curve has flattened” is extremely dangerous.  All universal quarantine does is brute-force stop transmission.  It doesn’t magically make people more immune. It doesn’t magically make the disease vanish from the planet.  Universal quarantine obviously will be effective in stopping transmission, which will, obviously, lower infection rates and death rates, and just as obviously ending quarantine will simply dump a still susceptible population into a, once again, high transmission environment and, of course, case rates and death rates will rise.  Quarantine can be safely relaxed when other effective mitigation strategies are in place and working. Optimally, a staged series of incremental relaxations, each expected to raise transmission rates by some manageable amount offsetting a reduction achieved by a more economically viable intervention should be phased in while monitoring the results.  Any step that pushes transmission rates beyond what can be managed should be rescinded until additional effective mitigation protocols are in place.

It isn’t hopeless – management is possible, even absent a miracle like UVC suppositories or bleach injections.  One might think of the problem this way:

A) You have some density of infectious people,

B) You have some density of susceptible people,

C) You have some rate of transmission between the infectious and the susceptible,

D) you have some rate of death due to the infection.

The combination of A, B, and C is the Rate of Transmission, R₀. As long as this is above 1.0, the infection grows.  There’s some level of “D” that we’re willing to tolerate where R₀ doesn’t matter.  In most countries, D seems to increase with R, from a nearly tolerable level to a level that we’re not willing to tolerate.  Therefore the goal is simply to intervene to control R₀ so that D is as acceptable as it can reasonably be.    Not so tricky.   But we have to keep in mind that some solutions are sustainable and tolerable and some are not.  We could just execute everyone with a fever.  We could just lock everyone into their homes and execute anyone who steps outside.  We could also just burn down the homes of any infected person with the family inside (a la Milan c 1350). While any of these would be quite effective and, if instituted globally would eradicate the virus; some solutions might not be acceptable in all regions.

We know for sure now that universal quarantine, even without martial law, does control R₀ quite well by only managing C, but only for so long before it falls apart and becomes unacceptable.  We also know for sure now that even one infectious person (A) interacting with an unprotected population (B), under “normal” interaction conditions (C) results in catastrophic values for D.  It is not rational to believe A will ever be zero.

So we need to find something other than universal quarantine, something that is sustainable that reduces A, B, and/or C such that R₀ is low enough that D is acceptable.  B will decline naturally as the percentage of the surviving population is “recovered,” and will do so fastest in those regions with the highest rates of infection, therefore, the level of control, C, necessary to keep D in check will decrease over time even without an advances in treatment.  Further, there isn’t only one solution to C: there are many ways to achieve lower transmission rates; we need to find those that match regional infection rates to regional medical capacity at the lowest economic cost.

While there may be a perfect solution to any one of ABCD someday, that’s highly unlikely.  But it isn’t needed if there are sufficient yet acceptable partial solutions to all that work together to get D where we can live with it:

A) Accessible testing, contact tracing, wide-area temperature screening, serum testing, etc. all help to reduce A, the density of the infectious.  None of these have to be perfect, all any has to do is selectively preferentially identify the infected out of the uninfected and include a mechanism for isolating them and it helps reduce A, the effective density of the infectious—it might not be a “solution” in and of itself, but it doesn’t have to be.  Detection only works if there’s a tolerable mechanism for isolating the infected from the interaction pool but this really shouldn’t be hard or economically untenable given we isolated everyone and most people have neither starved nor died unnecessary at home from conditions normally treatable. The better targeted and the more constrained (in breadth and time) the isolation, the lower the economic impact, but of course at a cost.  Balancing the cost of isolation interventions with efficacy is dynamic..

B) Identification of those particularly likely to suffer adverse outcomes and isolating them specifically rather than everyone should, it seems from data so far, be a possible way to reduce D substantially in a selective and therefore more sustainable way.  This means gathering more data on co-morbidity, screening, and providing targeted isolation and support for those at risk.  As above: everyone is isolated now and it hasn’t collapsed the world yet; selective isolation of the susceptible is less effective but more sustainable.   Most importantly, the more people who get sick and recover the lower the ratio of susceptible people will be; this is the only reliable end game.  As time goes on, it is reasonable to believe the ratio of recovered will rise and become the most significant “intervention” in reducing transmission.

C) So far as I’ve seen (and WHO reports) the only mode of statistically meaningful transmission is droplets and direct contact, neither airborne nor delayed contact shows up in transmission analysis.  While there may be indirect transmission by fomites or airborne transmission occasionally, the rate is so low as to be lost in the noise of the data available.  This suggests that relatively sustainable mechanisms will be able to effectively mitigate C, such as universal outgoing breath filtering masks on the potentially infected population (meaning simple masks that capture droplet spray for just about everybody for now), input filtering masks on the most vulnerable susceptible population (meaning N95 grade masks to block ingestion of viral particles), wide spread hand washing and sterilization protocols, and other interventions as transmission routes are validated.

D) In time, research on infection rates will improve understanding of disease progression and validate effective interventions to mitigate it.  The better this works, the lower the cost of allowing people to get sick and the more rapidly we can allow people to transition from susceptible to recovered.

It will take some carefully controlled epidemiological work and a lot of involuntary human experimentation to find a combination of factors that simultaneously optimize C19 mortality rates and economic viability, but that is just science and does not rely on any miracles.  It will, for sure, be less than full lock down.  It will not, for sure, be “back to normal”—at least not until 70% or so of the population has recovered—and that’s assuming at least long-term immunity, which may not happen.  If long-term immunity isn’t conferred by recovery, a balanced combination of interventions is sustainable indefinitely, though obviously not ideal.

Lock down is already ending intentionally and catastrophically.  In the US this is without any rational follow on plan, just “oh well, lets see what happens.”  This is not a mystery… recovered rates are about 1-4% or so by now, which is utterly insufficient for herd immunity to meaningful reduce “B” and justify ending meaningful control of “C.”  Places that “go back to normal” will be disasters in 3-5 weeks.  That will, alas, set back more rational plans to relax universal quarantine, which are needed and must happen to minimize the consequences of an economic catastrophe.   Germany is, intelligently, focusing on Re and health care load.  They got Re to 0.7, started relaxing, and now it is back up to 1.0.  At Re 1.1, Merkel estimates health care fails in Oct and at Re 1.3 in June. A rise in Re with the relaxation of isolating interventions is expected—the research we need is to provide an understanding of which interventions have the highest benefit:cost ratio.

Perhaps by late summer or early fall people will start realizing this is a long term problem and we have to find a way to live with it and various sustainable mitigation combinations might be tried and those that are successful understood and those that are not abandoned.  Until then, the world is fumbling blindly.

I suspect that within a year there will be a “new normal” that permits some travel (at least with carte jaune for the recovered) and fairly normal commerce.  I expect unemployment rates to peak around 40%, widespread global food insecurity, weaker governments will topple and there will be regional wars intensifying, which is already happening, and new wars emerging.  Intrinsically social businesses will remain or return to being outlawed in those areas were law still holds force (I am pretty confident the entire US will be relatively stable as will most developed countries).  This means no (sit down) restaurants, bars, clubs, movies, etc.  Population mortality rates in stable areas will be around 1% of total population but in regions without sufficient stability it will be 10%+.  Regions that “fail” will be problematic sources of unrest, terrorism, and reservoirs of disease for many, many years to come as even the recent marginally effectual international interventions will be far less economically viable for the countries that have historically provided aid.

Herd immunity will become meaningful in about a year in unstable regions with about 5%-10% loss of total population.  In stable regions, herd immunity might reach 30-40% in this time, sufficient for meaningful improvements in social constraints.  Unemployment will begin to decline after it peaks in about year, though there will be intermediate rises as falls as intervention mechanisms are tested and some fail; I anticipate in this time stable regions will move into optimistic territory and start rebuilding, though it will be a long process.

I’d think that within 3-5 years there will be sufficient global herd immunity that in combination with mass screening protocols that will be “normal” by then and with protective protocols for the most vulnerable, most people will interact socially and economically more or less as we remember we used to.  I doubt total population reduction will be much more than 2-5%, mostly driven by the poor who were made homeless/resource-less due to economic dislocation; the wealthy will get through with 0.5-1.0% total loss.  I’d think by this time we’d have a post-plague restructuring of the economy mostly complete.  Flattening curves are very encouraging in most of the world, but those areas are locked down with universal quarantine; flattening curves are what should happen under such restrictions, but no underlying conditions have changed from when infection rates were rocketing up exponentially other than lockdown itself so if lockdown ends infection rates will also rebound.

The US may have to default though that depends on global outcomes.  I am dubious of the US’s ability to weather this well.  While economics isn’t a zero sum game, neither is it unbounded.  It is largely relative and the US is incurring massive debt under the assumption that it will be manageable because of the US’s historical economic position.  This depends on a market for US debt which depends on US economic capability relative to the rest of the world.  Asia was gaining fast on US economic hegemony and there has been ongoing pressure, exacerbated by the unpopular actions of the administration, to find an alternative to the USD as the reserve currency.  If this happens, US debt could collapse quite suddenly as the cost of equity-securitized debt creates a potentially catastrophic negative feedback loop that can unpredictably result in runaway inflation.   On the other hand, everyone hates China right now and come November the US might have less problematic leadership.  Should the US be the source of vaccine or effective medical intervention, the US could emerge as we did from WWII: as the provider of economic and military expertise to the successful regions of the world, even if this seems optimistic at the moment.

 

Posted at 07:41:55 GMT-0700

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