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  • Josh Schiffer

March 10, 2020

A few reflections:

The impact of society and policy on the spread of the epidemic is undeniable at this point. It is clear that the epidemic has spun out of control in Iran and Italy (https://www.theatlantic.com/…/italy-coronavirus-cov…/607729/), two countries with only moderate connectivity to China. Many countries & municipalities with massive connectivity to China (Taiwan, Vietnam, Hong Kong to name a few) have largely avoided substantial spread despite a high probability of multiple seeding events. China barely makes the top 10 countries in terms of new daily cases (https://twitter.com/kakape/status/1237105924659195905): through effective social distancing, they have largely prevented outbreaks in secondary cities outside of the Wuhan region. The US is teetering. Korea has many new cases but may be at a stage where the effective reproductive number (a real time measure of R0 which captures control measures and herd immunity when relevant which at present it is not) is less than one (https://www.cnn.com/…/south-korea-coronavirus-in…/index.html), meaning that while there will continue to be new cases, the local epidemic will not ultimately sustain itself.


Mathematical models are vital to predicting general trends and forecasting possible effects of interventions. The potential importance of social distancing all came from elegant models, many done by Ira Longini and Betz Halloran at the Hutch. Yet, no model could have predicted that Italy and Iran would be the 2 global hotspots of infection. Some of this may reflect bad luck for those countries (seeding events at the wrong place at the wrong time). However, the effects of local policy, governance and infrastructure are undeniable in my opinion. At the end of this, each country will have an undeniable report card on how well it did. --------------

I spent the last 72 hours frantically putting together a grant application to study the natural history of SARS-CoV-2 infection in extraordinary detail including the nature of the immune response during and after infection. Based on the situation on the ground in Seattle, the incredible work by the Seattleflu team over the last 2 years to set up a widespread testing infra-structure across the city, and an extraordinary team of multi-disciplinary scientists at Fred Hutch / UW / Seattle Children’s, we saw a unique opportunity and went for it Fingers crossed that we will get funded.


Grants are an extraordinary amount of work but much of it (formatting, following arcane budget protocols, subcontracts, letters of support, dealing with horrible bibliography software that invariably falters at the stroke of midnight) can feel like pushing water up hill. It has been surreal putting in 16-hour days on this project, isolated at home (our offices are closed), plucking away at my laptop, and knowing that only a few miles away, my close colleagues and friends are on the front lines managing a highly dynamic situation where we still don’t have the capacity to test everyone who needs it.


I have read reports that ER and ICU physicians and nurses outside of Milan are putting in 4-day shifts. It has been a few years since I have been a front-line provider in either of these settings. ICUs are exhilarating places to work when things are busy and complex but still under control. However, I also recall the feeling of losing that sense of control when unexpected surges of sick people arrived. It sucks. What is happening now is obviously on a different scale with the added risk of exposure to a viral pathogen. My thoughts are with those brave souls on the front lines. ------------------

On to today’s reading….at this point, there is so much good writing on the virus that it is increasingly difficult to make good recommendations. The top 5 articles in the Atlantic are COVID_19 related. All excellent. I’ll continue to try to select articles or news updates that resonated with me for one reason or another, or those that touch on under-reported trends.


A piece about local friends and colleagues Keith and Helen who have pulled off the impossible in the last 2 weeks. These are great scientists and even better people: https://www.nature.com/articles/d41586-020-00676-3


More great news from Seattle. This is such a fantastic idea and again evolves from the pre-existing infrastructure of the Seattlflu study. Thank you Bill and Melinda Gates: https://www.seattletimes.com/…/gates-funded-program-will-s…/


Important work showing that people can transmit for a day or 2 before becoming symptomatic. This is not surprising but does present a challenge for containment. It is interesting that the WHO is increasingly saying that fewer cases are completely asymptomatic than previously thought (children may be a notable exception). So it might be that infected people who are not yet symptomatic account for ~50% of new transmissions: https://www.medrxiv.org/conte…/10.1101/2020.03.05.20031815v1


Please use this information . The line between symptomatic and asymptomatic is often blurry. We have all been there…. feeling “pre-sick” and hoping that it is the result of too little coffee or sleep, or too much food, alcohol or exercise, rather than a true illness. The message is that if you feel even slightly crappy, please avoid others, particularly vulnerable populations.


From Germany, the first shedding study of healthy, infected people I have seen. See figure 2. Lots to digest here. The symptom duration is pretty short. It looks like there is shedding well beyond the symptomatic phase in the mouth, sputum and stool. It is also unclear if this is enough virus to transmit or not. Importantly, the graphs show viral RNA which includes all RNA which overestimates the amount of actual infectious virus, which was in turn difficult to detect at later timepoints, particularly in stool. One small critique of this important study is that they did not do nasal swabs: https://www.medrxiv.org/…/10…/2020.03.05.20030502v1.full.pdf


It warms my heart to see this type of data. I am not sure who did the first mucosal swab to detect viral nucleic acids. However, the first large scale studies were done by mentors Anna Wald and Larry Corey for the study of oral and genital herpes, in hundreds of study participants over many weeks. Measuring and trying to understand serial measures of viral loads of HSV, but now ~10 other viruses, is more or less my job. For the first several years of my career, it was sometimes a challenge to sell the importance of this type of work. It is wonderful to see this type of data go fully mainstream.


One last tweet from David Roth, the world’s best writer on baseball cards from the 1980s and also the psyche of Donald Trump: https://publish.twitter.com/…


As always, opinions expressed are my own and today somewhat hastily written on not so much sleep. Feel free to share with friends and family.

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