Chances of a COVID-19 Vaccine

“The objective is to calculate risk profiles for vaccines targeting human infectious diseases. A database was actively compiled to include all vaccine projects in development from 1998 to 2009 in the pre-clinical development phase, clinical trials phase I, II and III up to Market Registration. The average vaccine, taken from the preclinical phase, requires a development timeline of 10.71 years and has a market entry probability of 6%.”

-Pronker ES, Weenen TC, Commandeur H, Claassen EHJHM, Osterhaus ADME (2013) Risk in Vaccine Research and Development Quantified. PLoS ONE 8(3): e57755. https://doi.org/10.1371/journal.pone.0057755

A pandemic changes the risk profile in the sense that figuring out whether a vaccine is profitable is no longer the key consideration. However, it is worth noting that the current record for vaccine development is for Ebola, which took five years. And what about the original SARS? We still don’t have a vaccine for it, or for any coronavirus.

But, what about the recent news about Moderna’s vaccine? It’s based on mRNA. Let’s see what the CEO of one of the largest vaccine manufacturers in the world had to say on the topic, over a month ago:

“[GSK CEO Emma Walmsley] noted that mRNA vaccine candidates, such as the vaccine Moderna Inc. (NASDAQ:MRNA) is developing, have gotten into clinical trials more rapidly than those based on more conventional approaches, but there is some uncertainty about mRNA technologies.

“We are seeing several mRNA candidates coming forward,” Walmsley noted. “They may get earlier visibility of results. These are new technologies that haven’t been manufactured at scale.”

“Messenger RNA is a promising technology; it’s very versatile and it can produce candidates relatively quickly,” Loew said. “It has, however, never been tested in large Phase III trials and there is also no registered vaccine available today using that technology. It remains to be seen what this technology can really deliver.”

-Steve Usdin, “As COVID-19 vaccines progress, science and policy questions become more urgent.” BioCentury. April 15, 2020.

There are many coronavirus vaccine prospects, with frontrunners and others. Many different approaches are being tried to develop a vaccine. But, the target of getting one that works, is safe, can be manufactured and distributed at scale, and is available before the pandemic has run its course is not something that is likely to happen. Even if it were, it won’t be this year. Odds aren’t good for next year either.

Let’s hope a vaccine can be developed in time. But, let’s also be clear-eyed about the chances of that happening. They aren’t good.

Harvard’s Reinhart and Rogoff Say This Time Really Is Different

“And you want to talk about a negative productivity shock, too. The biggest positive productivity shock we’ve had over the last 40 years has been globalization together with technology. And I think if you take away the globalization, you probably take away some of the technology. So that affects not just trade, but movements and people. And then there are the socio-political ramifications. I liken the incident we’re in to The Wizard of Oz, where Dorothy got sucked up in the tornado with her house, and it’s spinning around, and you don’t know where it will come down. That’s where our social, political, economic system is at the moment. There’s a lot of uncertainty, and it’s probably not in the pro-growth direction.”

-Simon Kennedy, “Harvard’s Reinhart and Rogoff Say This Time Really Is Different.” Bloomberg. May 18, 2020.

Probably the best thing I’ve read on the financial implications of the coronavirus pandemic. If you have any interest in GDP, the economy, etc., this is worth reading in full.

Knowledge of the Future

“…there are (a) facts, (b) informed extrapolations from analogies to other viruses and (c) opinion or speculation.

…if you’re experiencing something that has never been seen before, you simply can’t say you know how it’ll turn out.

…There’s no algorithm for deciding whether to favor life for a few (or for thousands) versus economic improvement for millions.”

-Howard Marks, “Knowledge of the Future.” Oaktree Capital. April 14, 2020.

Interesting throughout.

Grim News: Cutting Through the COVID-19 Bullshit

Flu pandemics for the last 250 years have had two peaks. Weather does not appear to effect their severity. Original assessment of the basic reproductive number, i.e., R0, of COVID-19 was ~2.5, with the Wikipedia entry on herd immunity citing a possibility as low as 1.4.

But, R0 of COVID-19 has been reassessed, and it is now thought to be ~5.7. This is important because at 1.4, it has low transmissiblity. Only 29% of people need to have had the disease and recovered to break chains of transmission. As R0 increases, so does the percent of the population required for herd immunity, i.e., R0 of 4, requires 75% immunity, 5 is 80%, 6 is 83% and 7 is 86%. As a point of comparison, Spanish Flu had an R0 of ~2.

Without a vaccine or effective treatment that can be produced at scale, you want to reduce the infection rate to get to herd immunity at a slower pace. By reducing the burden on health care systems, you also reduce the number of people that die because they cannot get modern medical care. As time is shortened, less people get care and more people die. It’s the idea behind “flatten the curve”. More time also means more time to develop some kind of treatment or a vaccine to get to herd immunity without so many dying or even getting the illness.

The important questions right now are: (1) How many people have been infected, since some were either asymptomatic or had mild symptoms? (2) Of people infected, how many died?

The initial results from the first “sero-surveys”, that is blood tests taken from a representative sample of a population looking for antibodies that indicate a person had COVID-19, indicate herd immunity is ~15% for a population that have been through their first peak and the death rate from COVID-19 when hospital systems are not overwhelmed is ~0.4%.

So, why is the above important? It means to get to herd immunity, something like 82% of people will have to get infected and of those that get infected, 0.4% will die. Then, we can calculate:

Population * Percentage of People For Herd Immunity * Death Rate = Deaths

In the case of the United States, that works out to something like:

341,000,000 * .82 * .004 = 1,118,480 U.S. deaths

If you look at the entire world and assume the fatality rate doubles on average because of how much of the world does not have access to healthcare, you get:

7,800,000,000 * .0.82 * .008 = 51,168,000 worldwide deaths

And with this knowledge in hand, when the yahoos in government tell you that “their model” indicates that only 60,000 people will die in the U.S., that things can go back to normal after a few weeks of “shelter-in-place” and May is a good time to restart the economy, you’ll know that you are being bullshitted.

The reality is that May will be the down slope of the first peak. The crisis will continue through the summer at a lower level and likely have a second peak in September/October. Given how badly it is being handled in the United States, we will reach herd immunity faster, with all the additional fatalities that entails.

Wait for the serological tests in the United States to look like the German ones that have already been done, and hopefully, in a sane world, a “pivot” back to something like the grim reality of what we are dealing with here by what passes as the U.S. federal “government”.

“Some limited data support a potential waning of cases in warmer and more humid seasons, yet none are without major limitations. Given that countries currently in “summer” climates, such as Australia and Iran, are experiencing rapid virus spread, a decrease in cases with increases in humidity and temperature elsewhere should not be assumed. Given the lack of immunity to SARS-CoV-2 across the world, if there is an effect of temperature and humidity on transmission, it may not be as apparent as with other respiratory viruses for which there is at least some pre-existing partial immunity. It is useful to note that pandemic influenza strains have not exhibited the typical seasonal pattern of endemic/epidemic strains. There have been 10 influenza pandemics in the past 250-plus years – two started in the northern hemisphere winter, three in the spring, two in the summer and three in the fall. All had a peak second wave approximately six months after emergence of the virus in the human population, regardless of when the initial introduction occurred.”

-National Academies of Sciences, Engineering, and Medicine. 2020. Rapid Expert Consultation on SARS-CoV-2 Survival in Relation to Temperature and Humidity and Potential for Seasonality for the COVID-19 Pandemic (April 7, 2020). Washington, DC: The National Academies Press. https://doi.org/10.17226/25771.

“”Initial estimates of the early dynamics of the outbreak in Wuhan, China, suggested a doubling time of the number of infected persons of 6–7 days and a basic reproductive number (R0) of 2.2–2.7. We collected extensive individual case reports across China and estimated key epidemiologic parameters, including the incubation period. We then designed 2 mathematical modeling approaches to infer the outbreak dynamics in Wuhan by using high-resolution domestic travel and infection data. Results show that the doubling time early in the epidemic in Wuhan was 2.3–3.3 days. Assuming a serial interval of 6–9 days, we calculated a median R0 value of 5.7 (95% CI 3.8–8.9).”

-Sanche S, Lin YT, Xu C, Romero-Severson E, Hengartner N, Ke R. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020 Jul [April 11, 2020]. https://doi.org/10.3201/eid2607.200282

“From the result of their blood survey, the German team estimated the death rate in the municipality at 0.37% overall, a figure significantly lower than what’s shown on a dashboard maintained by Johns Hopkins, where the death rate in Germany among reported cases is 2%.

The authors explain that the difference in the calculations boils down to how many people are actually infected but haven’t been counted because they have mild or no symptoms.”

-Antonio Regalado, “Blood tests show 14% of people are now immune to covid-19 in one town in Germany.” MIT Technology Review. April 9, 2010.

Someone Needs to Ventilate the Air From the Smell of Bullshit

“Ford Motor Co said on Monday it will produce 50,000 ventilators over the next 100 days at a plant in Michigan in cooperation with General Electric’s healthcare unit, and can then build 30,000 per month as needed to treat patients afflicted with the coronavirus.”

—Nick Carey, “Ford, GE to produce 50,000 ventilators in 100 days.” Reuters. March 30, 2020

It’s a good idea, sure. But, peak effects from the coronavirus in the United States will have largely passed in the next hundred days. Most of these ventilators will need to be shipped to Africa, Latin America, India and elsewhere. Hopefully, they’ll keep some around for when this thing gets bad again (but not as bad as now) in October.

Is Now a Good Time to Trip on Psychedelics?

Vice.com asking the important questions. My initial reaction was, “Of course not.” And, “No,” appears to be the ultimate conclusion of the article. But, perhaps a more interesting question than it seems at first.

“It’s sometimes said that a proper trip takes three days: one to prep (especially if you follow more severe protocols around fasting beforehand), one for the trip itself, and one to come down and re-acclimatize to the rigours of reality, which are themselves these days all totally out of whack. Using the time alone to experiment with psychedelics and explore your own interiority seems like a handy idea during this bizarre period of consensual social lockdown…

…Hubbard’s insight was that cultivating comfortable environments would result in drastic, and ideally positive, shifts in the psychedelic experience itself.

The idea was codified in 1964’s The Psychedelic Experience: A Manual Based on the Tibetan Book of the Dead, co-authored by Leary, Ralph Metzner, and Richard Alpert. ‘The nature of the experience depends almost entirely on set and setting,’ they write, straight off the top. ‘Set denotes the preparation of the individual, including his personality structure and his mood at the time. Setting is physical—the weather, the room’s atmosphere; social—feelings of persons present towards one another; and cultural—prevailing views as to what is real.'”

-John Semley, “You’re Socially Isolating. Is Now a Good Time to Trip on Psychedelics?” Vice.com. March 26, 2020.

See also: Who the Fuck is SWIM?

Coronavirus Disease (COVID-19) – Statistics and Research

“The purpose of this article on COVID-19 is to aggregate existing research, bring together the relevant data and allow readers to make sense of the published data and early research on the coronavirus outbreak.”

https://ourworldindata.org/coronavirus

When you get tired of listening to people that don’t know what they are talking about blather on about epidemics, cures or whatever, take a look at this site for a good overview of the state of the coronavirus data.

A Mass Message From My Doctor

Thought I’d pass this along in case your doctor isn’t as good as mine. Unsolicited, fantastic advice that everyone should read.

“Coronavirus and Clinic Updates:  

…The crisis of Coronavirus is the exponential growth. The number of cases are increasing 30% per day. So however many cases we have today, we will have 10 times as many in 10 days and 100 times as many in 20 days. We worry about having enough hospital resources to care for folks if the outbreak spreads too fast. As you can imagine our health care system will be challenged. Many of us are taking extra shifts in the hospital. This week is calm, but I suspect the next month will be difficult.  

As long as a sick person does not cough into your face, masks won’t help much. The way most of us will get this virus is by touching it with our hands and then touching our face. It seems to be spread by mucus on hands, and its also found in stool. So basically it’s spread like the flu (respiratory droplets) and spread like norovirus (stomach flu). And it’s much more severe. And it can be spread before you feel sick. So it’s basically a perfectly designed virus. Not good for us.  

Many patients will be contagious for days before they ever feel sick, and can spread it by touching doorknobs or preparing food for others. [Note: The CDC says there isn’t any evidence that coronavirus can be transmitted through food. He’s a good doctor, but no one’s perfect.] This is why hand washing and staying away from other people are the two primary ways to avoid covid. Masks help the sick person not spread covid, but they don’t prevent healthy people from catching it. So please save the masks for health care workers.  

If you get a cough and fever, you could have COVID and you should call to discuss. Especially as flu season winds down, the likelihood of COVID as the cause of fever will go up. Most patients don’t need to be tested, you just need to self quarantine and stay away from other people. As testing becomes easier to get, we may start testing everyone – but we are not there yet. Still a huge backlog. The major reason to get tested is if you have to work; Or if you are risk factors for a poor outcome: age > 60, diabetes, heart disease, lung disease, cancer, HIV, weak immunity.

If you get severely short of breath, you should call our office or go to the ER. Generally, this would not happen all of a sudden, it’s usually after being sick for 7 days. Patients with covid who get sick, go from initial symptoms to needing the intensive care unit on day 7 -10. So it takes some time. Most young healthy people will never need to see a doctor. We are sending the majority of covid + patients home…Mortality in the USA is still only 1%. Mortality is greater when older than 60. And especially over 80. So keep grandchildren away from grandparents[.] Young kids do not seem to get sick, they can still carry the disease and transmit to others who might have risk factors.

A new symptom being described is loss of taste or smell. In South Korea where they tested widely, 30% of covid patients had loss of taste or smell, even without fevers. So if you have that symptom, you may not get sick but you are contagious, so avoid people for 14 days, wash those hands like crazy. Most people get sick within 5-6 days of exposure, but some take as long as 14. Which is why we’re using 14 days as an estimate for quarantine.

Information and thoughts about moving forward are changing every day. I encourage you to get your medical information from Dr. Fauci and other medical and public health experts, not from politicians or pundits. The CDC’s website has great (and scientifically accurate) information. I hope this has helped…”

Don’t Panic: The Comprehensive Ars Technica Guide to the Coronavirus

“This new coronavirus—dubbed SARS-CoV-2—is unquestionably dangerous. It causes a disease called COVID-19, which can be deadly, particularly for older people and those with underlying health conditions. While the death rate among infected people is unclear, even some current low estimates are seven-fold higher than the estimate for seasonal influenza.

And SARS-CoV-2 is here in the US, and it’s circulating—we are only starting to determine where it is and how far it has spread. Problems with federal testing have delayed our ability to detect infections in travelers. And as we work to catch up, the virus has kept moving. It now appears to be spreading in several communities across the country. It’s unclear if we will be able to get ahead of it and contain it; even if we can, it will take a lot of resources and effort to do it.”

—Beth Mole, “Don’t Panic: The comprehensive Ars Technica guide to the coronavirus.” Ars Technica. March 11, 2020.

Beth Mole’s science writing is on point. But, let’s not lie to ourselves. This idea that the United States is going to contain this pandemic is nothing short of fantasy. By May, there will be hospital crises across the country, and it will likely resurge in October after a summer lull. Best to accept this as fact.

Cryptic Transmission of Novel Coronavirus Revealed by Genomic Epidemiology

“The field of genomic epidemiology focuses on using the genetic sequences of pathogens to understand patterns of transmission and spread. Viruses mutate very quickly and accumulate changes during the process of transmission from one infected individual to another. The novel coronavirus which is responsible for the emerging COVID-19 pandemic mutates at an average of about two mutations per month. After someone is exposed they will generally incubate the virus for ~5 days before symptoms develop and transmission occurs…

…We believe this may have occurred by the WA1 case having exposed someone else to the virus in the period between Jan 15 and Jan 19 before they were isolated. If this second case was mild or asymptomatic, contact tracing efforts by public health would have had difficulty detecting it. After this point, community spread occurred and was undetected due to the CDC narrow case definition that required direct travel to China or direct contact with a known case to even be considered for testing. This lack of testing was a critical error and allowed an outbreak in Snohomish County and surroundings to grow to a sizable problem before it was even detected.

Knowing that transmission was initiated on Jan 15 allows us to estimate the total number of infections that exist in this cluster today. Our preliminary analysis puts this at 570 with an 90% uncertainty interval of between 80 and 1500 infections

…We know that Wuhan went from an index case in ~Nov-Dec 2019 to several thousand cases by mid-Jan 2020, thus going from initial seeding event to widespread local transmission in the span of ~9-10 weeks. We now believe that the Seattle area seeding event was ~Jan 15 and we’re now ~7 weeks later. I expect Seattle now to look like Wuhan around ~1 Jan, when they were reporting the first clusters of patients with unexplained viral pneumonia. We are currently estimating ~600 infections in Seattle, this matches my phylodynamic estimate of the number of infections in Wuhan on Jan 1.”

Trevor Bedford, “Cryptic transmission of novel coronavirus revealed by genomic epidemiology.” Bedford Lab. March 2, 2020.

Roughly speaking, the take-away from this article is that 9-10 weeks after you have cases in your area, you should expect widespread transmission. The article outlines things you can do to minimize your risk of exposure:

  • Practicing social distancing, such as limiting attendance at events with large groups of people
  • Working from home, if your job and employer allows it
  • Staying home if you are feeling ill
  • Take your temperature daily, if you develop a fever, self-isolate and call your doctor
  • Implementing good hand washing practices – it is extremely important to wash hands regularly
  • Covering coughs and sneezes in your elbow or tissue
  • Avoiding touching your eyes, nose, and mouth with unwashed hands
  • Disinfecting frequently touched surfaces, such as doorknobs
  • Beginning some preparations in anticipation of social distancing or supply chain shortages, such as ensuring you have sufficient supplies of prescription medicines and ensuring you have about a 2 week supply of food and other necessary household goods.
  • With these preparation in mind, it is important to not panic buy. Panic buying unnecessarily increases strain on supply chains and can make it difficult to ensure that everyone is able to get supplies that they need.