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  • Josh Schiffer

March 16, 2020


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A friend from Viet Nam sent me this article today (https://southeastasiaglobe.com/coronavirus-life-inside-a-vietnamese-government-quarantine/). To those who have followed my thread, it is very clear that I am fascinated by the fact that certain countries have had different outcomes than others. This article highlights that Viet Nam’s success has not come easily.


I’d also like to focus on one point in the article where things almost hit a boiling point in the airport. Thankfully, cooler heads prevailed, and everything worked out with successful and appropriate quarantine. My impression is that similar experiences are likely to happen to many of us in the upcoming weeks. You should be preparing yourself for long lines, delayed care of sick relatives and friends where the communication will not feel perfect, possibly meaningful shortages and the possibility of personal discomfort of one variety or another.


This is not to sound alarmist but just to allow you to prepare. My advice is to find some time before the storm hits, take a walk, and envision these situations happening to you. Do not simply imagine that this will all pass without any personal consequence. Hopefully it will. Then you can call me and give me a hard time for stressing you out a bit. However, we have no collective experience with what is about to hit us, which makes imagining the worst very difficult to do.


Before it happens, remind yourself that if you are in an immensely frustrating situation, that the person who seems to be letting you down in some way, is likely without options and has been under great personal stress for hours and probably days. Find your inner reserves of grace and humor. We need everyone to be at their best and showing up emotionally prepared will really help.


Our local hospitals are already there. Everybody knows that it will be worse next week. I am so proud of my brave colleagues on the front line.


Aequanimitas: https://medicalarchives.jhmi.edu:8443/osler/aequessay.htm


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Topics today:

Up to date country specific projections: It is natural to follow the death counts and the number of absolute cases. I do. It is appropriate to look at this data and feel shocked, saddened or relieved (depending on which country you are observing).


However, to understand what is most likely to happen NEXT, look at the regional reports section in this incredible document:

https://cmmid.github.io/topics/covid19/current-patterns-transmission/global-time-varying-transmission.html


You will find country specific reports of R0 & doubling time. The goal is R0<1 which I am only seeing in Korea & China. There are a lot of countries flirting with R0~1. This is a mathematically interesting spot where we would expect smoldering infection that does not die out but is not widespread: this seems like a plausible outcome from the flatten the curve approach.


Please note the 95% uncertainty bounds around R0 & the doubling time. The US could vary from 1-2 which means we still do not have a grasp on the trajectory of our current national epidemic. More, data, please.


To grasp how different countries are from one another, look at them individually. In Italy, the US & Western Europe, R0 started out tragically high but the effects of physical distancing are now obvious. Hong Kong and Singapore started out low and stayed there but remain slightly >1. Secondary cities in China started below 1 and are now creeping up to smoldering infection levels, likely with slight relaxation of physical distancing:


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Cell phones as a tool for culling the epidemic: Christophe Fraser is one the smartest people I have ever met. I had a couple of beers with him in London when he was teaching me about R0 at Imperial College. He is so understated and modest that at times, the brilliance of what he is saying can be missed on first pass. It is no surprise that Christophe is already thinking with a clear head about best next steps. The 4th slide in his thread is such a simple but lovely idea, breaking down R0 into its components over time in terms of who is spreading the virus and when (ie asymptomatic people, pre-symptomatic people and symptomatic people). His cell phone notification approach may hit this curve in its sweet spot to get R0<1. And he is considering the best ethical approach as well

https://twitter.com/ChristoPhraser/status/1239638261938761730

https://github.com/BDI-pathogens/covid-19_instant_tracing


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Looking for a signal. The typical way that influenza is tracked each season is primitive yet practical: counting the number of people who present with influenza like symptoms over time. (Testing for influenza is regional and inconsistent making this an imperfect method). This method is somewhat imprecise as lots of other infections can cause these symptoms, but overall is quite predictive of influenza levels at a given time in a given year. These researchers are seeing an unusual bump in the data. There is no doubt in my mind this is COVID which is now widely spread. In a week, the bump will be a large hill I am afraid: https://github.com/reichlab/ncov/blob/master/analyses/ili-labtest-report.pdf


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Public health is honorable & cool profession. I continue to hope that a silver lining from this crisis is that public health professionals will be recognized for the stars who they are, and that we will ultimately focus a bit more on prevention than cure going forward. Read this article & look at the graphics. It is just amazing work from Korea: https://graphics.reuters.com/CHINA-HEALTH-SOUTHKOREA-CLUSTERS/0100B5G33SB/index.html


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Physical distancing. This is still the key. Please do it. I won’t bludgeon you any further with this concept, but this article provides some helpful advice. A key point is to get outside and take a walk. No risk of infection from getting some fresh air. https://www.usatoday.com/story/opinion/2020/03/16/coronavirus-social-distancing-myths-realities-column/5053696002/


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The UK & Herd immunity. This story is getting attention because Boris said some stupid things. As mentioned in the thread and the article, herd immunity is not a sane goal but and would be an unfortunate outcome. Herd immunity happens when a single person who is infected becomes less infectious, because the a higher % of the people they come into contact with are already infected or resolved / immune. To get to this point, you need to have already had a ton of infection in the population. The other possibility is to implement an effective vaccine widely: the cool thing about herd immunity after a vaccine is that it provides indirect protection of the unvaccinated, even anti-vaxxers!! However, in the absence of a vaccine, saying that your goal is herd immunity is really dumb and dangerous with this particular epidemic. A synonymous sentence would be… we are going to let the virus run its course. As I mentioned before, this means a level of suffering well beyond what has happened in Italy with no medical care for most sick people and a large die off in the elderly. This is not really what the UK has planned I suspect. However, even a slight delay in physical distancing would be a terrible strategic error in my view:

https://twitter.com/AdamJKucharski/status/1238821515526897664


https://www.theatlantic.com/health/archive/2020/03/coronavirus-pandemic-herd-immunity-uk-boris-johnson/608065/


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Seasonality: The jury is out on whether there will be partial or no seasonality for SARS-CoV-2. In the transplant ID field, we have been focused on this topic for years. After a stem cell transplant, typically wimpy respiratory viruses can be fatal and aggressive ones can be too. This is scary because we don’t have good antiviral drugs for the viruses which most often cause the common cold. As a result, we follow different viruses each year and certain players are more governed by seasonality (RSV, influenza) than others (parainfluenza). The biology underlying this is complicated and sometimes controversial. A great review here:

https://www.sciencemag.org/news/2020/03/why-do-dozens-diseases-wax-and-wane-seasons-and-will-covid-19


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ACE inhibitors & SARS CoV-2: I am getting asked about this a lot as well. A longer biology thread will follow. Briefly, the receptor that SARS 1 & SARS 2 use to get in cells are also the target of common blood pressure meds, ACE inhibitors and ARBs. Data from China shows that coronary artery disease is a striking risk factor for death in infected people (more than emphysema surprisingly): https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930566-3. There is interest, therefore in using existing meds, or soluble forms of the receptor to bind the virus, to treat.


For now, my message is simple. No concept or medicine, however promising or cool in theory, can be properly tested in the absence of a clinical trial. There will undoubtedly be reports of patients getting better (and worse) with these agents, along with other Hail Mary approaches being tried around the world. I have no problem with Hail Mary attempts in critically ill patients. However, in the absence of a properly done, randomized clinical trial, we will not know the truth of whether the intervention works or not.


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Reinfection: I get a lot of questions about whether people are at risk of reinfection. The answer for the vast majority of people is very likely to be no. The LA times had an article suggesting that this phenomenon may occur, but the evidence is really weak. Most acute viral infections, particularly in the respiratory tract, are followed by at least a brief period of immunity. To prove re-infection in a person (and discriminate this from persistent infection or infection with another virus or bacteria) is devilishly challenging and requires sequencing of the first and second virus and showing they are different. This is a study in monkeys that were re-challenged with a high dose after the first infection and had not even a blip of detectable virus. Very clear proof of immunity:

https://www.biorxiv.org/content/10.1101/2020.03.13.990226v1.full.pdf


The more relevant question in the field is how long immunity lasts. We need to know this for 2021 & beyond.


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The economy. To be honest, I did not read this. I can only handle so much pain. The title makes me want to run through a brick wall:

https://www.nytimes.com/2020/03/16/opinion/coronavirus-economy-debt.html?action=click&module=Opinion&pgtype=Homepage


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Some great small things:

https://www.youtube.com/watch?v=JnbjACXp-SE&fbclid=IwAR1OdhobzixDf8qfxlTN2Ec8T7Bf4In4OjH5C44vNGudhzj5A_Wrn0JYTLo


https://twitter.com/rexchapman/status/1239245572206481412?s=12&fbclid=IwAR1cQ4_mTHx1MOlue_JVMsXjvCdoe8mtg6zU66xGx9Vml5ncJpS_6KrOTrs


https://twitter.com/YoYo_Ma/status/1238572657278431234



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