COVID-19: A Warning

On page 147 of the 1935 printing of Rats, Lice, and History, (pdf Archive.org ) epidemiologist Hans Zinsser writes about the Plague of Justinian,

“It is interesting to note that this epidemic displayed one of the characteristics so often referred to in modern epidemiology — namely, when the outbreaks begin, the number of sick and the mortality were relatively slight, but both rose with appalling violence as the epidemic gathered velocity.”

 It is understood that while worsening conditions of life in an epidemic exact a toll, the primary change is increase in the virulence of the pathogen.

Zinsser had personal experience with the notorious modern example, described in (NCBI PMC) The U.S. Military and the Influenza Pandemic of 1918–1919. Quoting (boldface  mine),

During Chesney’s first documented period, the month of June to July 27, the 5th Artillery Brigade had 77 “relatively mild” cases of influenza. During the second phase, July 27 to August 23, 200 men of the 58th Artillery Brigade became ill, about 6.5%. None of them died, but the outbreak was serious enough that the next brigade cleaned out the barracks, even washing the walls, before they moved in. Despite this precaution, during Chesney’s third phase, August 23 to November 8, more than one-third of the 6th Artillery Brigade, 1,636 soldiers, contracted influenza and 151 died. Chesney concluded that “…these successive outbreaks tended to be progressively more severe both in character and extent, which would speak for an increasing virulence of the causative agent.”

Like the stories of Zinsser’s captivating book,  this factual account omits the mechanics why virulence can increase. Since that time, epidemiology has evolved from a preponderance of mystery to an inexact science. In the past several months, epidemiologist have used a lot of hopeful words, with reluctance to make predictions. Only within the past week or so has CDC confided that COVID-19 is inescapable.

Like the social sciences, epidemiology lacks the bedrock of hard science master equations. But there is math; it just has to be tweaked to fit the circumstances.  The next article offers an intuitive approach to Zinsser’s assertion and Chesney’s experience. The predator-prey equations, explained in words, are a good place to start. Intuitive epidemiology is accessible to a large audience., including you.

The warning: In large parts of the world, particularly within conflict zones, but also without, conditions exist for an increase in the virulence of COVID-19.

To be continued shortly.

 

COVID-19, Live Vaccine Possible from Wild Serotype Overlap?

(CNN) First coronavirus death in Europe, with more than 67,000 cases globally,  features an interview with Kent and Rebecca Frasure, quarantined on the  cruise ship Diamond Princess. Print interview at  (Intelligencer) An American on Quarantined Cruise Ship Describes Moment His Wife Was Diagnosed With Coronavirus.

Despite what we expect as intimate contact on the cruise, Kent has not contracted COVID-19.  By itself, this registers as no more than an oddity. With that taken care of, Indonesia’s claim of zero  native cases (ABC, First case of corona virus linked to Bali after report Chinese tourist returned positive test). is no more than carelessness combined with wishful thinking.

But is it? If confirmed by more  instances, the explanations are limited to three:

  • Some people are genetically more susceptible than others.
  • Some groups have cultural practices that protect.
  • There are in circulation, one or more corona viruses with overlapping serotypes.

The serotype is the face the virus presents to the immune system. Viruses can share serotypes, either partly or completely, yet have different characteristics of infection. The common rabies virus is one example. Half a dozen common strains  have different clinical courses, but one vaccine is good for all.

The most famous case is smallpox. In 1796, Edward Jenner, a British physician, et al., promoted the fact that  immunity to smallpox was produced by inoculation with the live cowpox virus.

So there is precedent: a zoonosis immunizes against a human disease.  In Indonesia, a sero-similar virus could be endemic as a local version of the common cold. It could have developed by spontaneous mutation. But are there live animal markets in Indonesia?

Yes, there are. (Animals Asia) Animals Asia Ambassador Peter Egan visits “sickening horrors” of Indonesia’s brutal dog and cat meat markets. But domestic animals are not the historic reservoirs. Bats are more to the point. (ABC Australia) Coronavirus scare prompts call to pause bat meat consumption from Indonesian market.

The picture clarifies. With bats, dogs, and cats, civets and snakes are probably in the mix. A specialty coffee, kopi luwak, is made from beans in civet poop. Human processors of this material are exposed to a constant stream of civet viruses.

So a benign relative of COVID-19 may be present in the Indonesia community. Prior infection may produce the implied  immunity of Indonesians. Immunity caused by a live virus tends to be stronger and last longer than vaccine-induced.

Medical ethics has developed to protect the public from the worst abuses of the past. But it may have taken a turn towards avoiding liability. A simple thought experiment is Jenner’s smallpox vaccine.  Is there a modern path of ethical approval, save from a movie zombie attack, that would allow Jenner’s primitive vaccine, which worked?

It’s not hypothetical. The prospects for third world countries, and war zones, are dismal, unless they have their own fortuitous zoonosis. The analysis problem is not hard. It involves comprehensive sampling of circulating corona viruses in Indonesia, searching for similar serotypes.

There is a preliminary report from China that serum from recovered patients may be useful. A serum from “boosted” Indonesians could be a valuable export.  Or planeloads of sneezy Indonesians could fly to third-world destinations, and meet-and-greet, spreading benign relatives of COVID-19. See (bioRxiv ) Increased frequency of travel may act to decrease the chance of a global pandemic

You may be of conservative mind, rightly observing that you could lose your job with this.  For passive inclinations, there is still work. Detection or absence sero-similar relatives of COVID-19 in world populations offers refined estimates of the ultimate cost.

COVID-19; Do Travel Bans Make Sense?

In (CNN) Coronavirus cases rise to more than 64,000 globally, Anderson Cooper asks Sanjay Gupta whether travel bans make sense. Gupta’s reply seems to be in the negative, with a little vagueness thrown in.

Let’s nail it down. In the short term, travel bans have benefit. The benefit will decrease with time. It will be obvious when the utility of travel bans expires.

If people were like plants, did not travel, and could infect only their nearest neighbors,  an epidemic could be modeled as a pure diffusion process. Drip a drop of ink or food dye in a glass or water. Watch it spread out in the liquid, betraying the invisible currents of water in the glass. This is diffusion. The plume from a smoky fire is another form of diffusion, combined with convection.

The purest diffusion is equalization of temperature, between something which is hot, and something which is cold. But it’s almost always combined with something else. The cooling of your cup of coffee is a combination of diffusion, and air currents.  The currents are analogous to  travelers.

Now pour a fresh glass of water, add a drop of ink, and stir or shake the glass. This adds “travelers”, bulk movement of the water. The ink quickly spreads out through the water in the glass, until it all has the same tint. The ink in the glass will never concentrate again. That’s the past history of the ink, just as the current concentration of COVID-19 around Wuhan will be replaced by general prevalence.

The spread of COVID-19 is by a combination of modes:

  • Diffusion, as described above, by which a cluster grows locally.
  • Non local processes, which resemble stirring of the glass: an infected, asymptomatic  traveler, the “super spreader”.
  • Establishment of new clusters, which spread again by the above, diffusion and travelers.

Diffusion can be modified by sanitation.  Travel bans target the non-local modes. Eventually, COVID-19 will be equally present everywhere, subject only to local factors that have not yet been identified.

Travel bans buy time. The amount of time is impossible to predict.  At some unknown time, asymptomatic “super spreaders” will bypass bans. At that point, travel bans will become useless, but not before.  When is a roll of the dice. Politics will doubtless prolong the bans beyond usefulness, but that is future.

What do we do in the meantime? With a  fully functioning economy, we should be preparing, training, stockpiling, and researching. This is a time to screen small molecule drugs. For inspiration, (Science Daily) Dozens of non-oncology drugs can kill cancer cells. Quoting,

Researchers tested approximately 4,518 drug compounds on 578 human cancer cell lines and found nearly 50 that have previously unrecognized anti-cancer activity. These drugs have been used to treat conditions such as diabetes, inflammation, alcoholism, and even arthritis in dogs…

This kind of information, even in the negative, is vital to stave off quack remedies. From the debatable lore of medieval plagues,

Ring-a-round the rosie,
A pocket full of posies,
Ashes! Ashes!
We all fall down.[3]

 

 

 

 

 

Corona Virus, Incubation Period 24 Days?

(Reuters) Coronavirus cases outside China may be ‘tip of the iceberg’: WHO. Quoting,

Much remains to be determined about the virus, which has been linked to a market selling animals in Wuhan, the capital of Hubei province, including how easily it spreads and how deadly it is. Chinese researchers found that its incubation period could be up to 24 days….It had been thought to be up to 14 days. 

The maximum incubation period was thought to be a hard number. There may be no such number, invoking the scenario of the “caged virus.”

The caged virus phenomenon was first written about in conjunction with the rabies virus. Typical incubation periods are weeks, extending to months, occasionally up to two years. Then an isolated case of rabies with an apparent incubation period of 37 years was noted (citation missing.) The concept was further developed with the slow virus.

A slow virus replicates without effective immune response. Some trigger,  perhaps environmental, or possibly analogous to the bacterial quorum sensing, causes a switch from slow to fast.

No “slow” corona viruses have been discovered. There is no reason to think 2019-nCoV is the first one. But the 24 day incubation period, which may have measurement difficulties, suggests a gradation into that.

Most of the things epidemiologists are interested in cannot be derived from “first principles.” Observation is used to select a basic statistical model which can be adjusted. For example,

  • A uniform statistical distribution distributes the incubation period  evenly distributed up to a fixed limit, say, 14 days.
  • A Poisson distribution has an average incubation period, with tails in the direction of less and more.  It’s typical to cheat by chopping off the “more” tail, perhaps at 14 days, or 24. But this may not be valid.
  • We could be looking at a distribution without a practical upper limit for incubation. This doesn’t bother statisticians at all. There are many distributions with infinite variance.

It would mean we have blundered into a virus with a highly effective strategy, with widespread infected carriers, undetectable by any simple, practical means.

In 2019 Novel Coronavirus (2019-nCoV), Wuhan, China; Quarantine is Correct Response, I wrote,

Perhaps by tradition rooted in the 1976 swine flu fiasco, the cost of “no vaccine for 2019-nCoV ” is set for typical epidemiology. Yet the 1918 Spanish flu was untypically deadly for an airborne pathogen….The cost/benefit analysis could have an unpleasant surprise.

This could be that surprise.

 

 

 

 

2019 Novel Coronavirus in China, Lethality, Smoking & Genetics ?

As evidenced by the cruise ship quarantined in Yokohama, 2019-nCoV  is highly contagious, with no unexpected selectivity. The  lethality of the virus is still a question, which cannot be answered until the actual prevalence of subclinical and missed cases is tallied, which can only be accomplished when test kits are available and cheap.

Two factors may enhance the lethality of nCoV-2019 in China compared to the rest of the developed world, smoking, and genetics.

1. Smoking

In China, 60% of doctors are smokers, with rates in the general population said to be similar. Quoting from (Wikipedia) Smoking in China.

Nearly 60% of male Chinese doctors are smokers, which is the highest proportion in the world.[4] China does not have laws to punish health care facilities, medical workers and health officials who violate smoking bans, and is instead relying on the Chinese media to act as a watchdog.[4]

Smoking is a social custom in the PRC,[1] and giving cigarettes at any social interaction is a sign of respect and friendliness.

Now refer to (PLOS via NCBI) Effect of tobacco smoking on the risk of developing community acquired pneumonia: A systematic review and meta-analysis. From the abstract conclusion (square brackets mine):

Tobacco smoke exposure is significantly associated with the development of CAP [pneumonia acquired outside a hospital] in current smokers and ex-smokers. Adults aged > 65 years who are passive smokers are also at higher risk of CAP. For current smokers, a significant dose-response relationship is evident.

This is a meta-study.  Prior studies with varying endpoints were analyzed via statistical methods to remove confounding factors, isolating the association of smoking with pneumonia. Community acquired is the term for an infectious disease acquired anywhere other than in a hospital.

This study does not examine lethality, probably because statistical techniques  could not dig it out with sufficient confidence levels.  To see the likely connection, consider the structure of the lung. Two parts of the lung come in direct contact with air:

  • The bronchioles are air tubes, arranged like an upside down tree, decreasing in diameter the further in you go from the windpipe.
  • The alveoli are expandable balloons, attached to the bronchioles like the leaves of a tree. This is where oxygen exchange occurs.
  • Both are lined with respiratory epithelium, which is lined with fine motile hairs called cilia, and wet with mucus.

In a healthy nonsmoker, the cilia  “beat” to expel inhaled particles back up the bronchioles to the  throat, where they are expelled or swallowed, usually without notice.

In a nonsmoker, the innate immune system, which requires no prior knowledge of a virus, is active. (NCBI) Innate immunity and mucus structure and function. This is why, in most cases, an individual virus particle cannot cause infection. The number is small, but usually greater than one.

In a smoker, the actions of the cilia, and the innate immune system, are suppressed. Recovery from viral pneumonia is possible due to the adaptive immune system, which requires time to manufacture antibodies specific to the pathogen. It becomes a race in time, between viral load and antibody production.

So it is highly plausible, though missing study results, that a China where most people smoke, including doctors and staff, is likely to experience enhanced lethality due to 2019-nCoV.

2. Genetics

By strict definition, pneumonia is an infection of the alveoli, not the bronchioles which connect. Broadening the definition, it includes bronchiolitis. This is considered  clinically significant primarily with infants. There is an interesting exception, diffuse panbronchiolitis.

Diffuse panbronchiolitis is considered an Asian phenomenon,  which means that the etiology (cause) and prevalence are not nailed down. It is clinically known in Japan and Korea, with suspicion of a genetic influence.  The origins of these groups, like the rest of us, are lost in prehistory. Current theories of origin:

  • Koreans have a large genetic representation of tribes from eastern Siberia.
  • Japanese contain some of the above, as well as other groups.

This suggests that a genetic bottleneck in eastern Siberia  resulted in the frequency of diffuse panbronchiolitis in both populations.

In prehistory, the Han Chinese were in conflict and competition with every other adjacent group. While they remained culturally distinct, genetic isolation is unlikely. Literature suggests that the prevalence of this disease in China is unknown. A contributor to 2019-nCoV lethality  may lurk within this vacuum.

3. Coincidence of Factors

The combination of a possible genetic factor, and smoking, may be more than additive. It may be multiplicative .

The prevalence of smoking in and near health care facilities may enhance nosocomial (in a hospital) transmission.

 

 

 

(Reuters) To counter Huawei threat, U.S. should consider taking ‘controlling stake’ in Ericsson, Nokia -attorney general

(Reuters) To counter Huawei threat, U.S. should consider taking ‘controlling stake’ in Ericsson, Nokia -attorney general.

I have written about this before:

The danger is clear and present, yet the perception is not universal. A.G. William Barr’s case may not be obvious to everyone. Let’s explore.

Depending upon whether your attitude is young or old, and the expansiveness of your world-view,  you might still be living in ghostly remains of the Second Industrial Revolution.  Historians say it ended around 1914, but it left the idea that what matters can be measured in tons, watts, and British Thermal Units. The time that followed hasn’t been formalized by historians. But it features the increasing immateriality of assets of all kinds.

You can use a modern smartphone without grocking this. On one level, it’s just another plasticky,  blingy thingy that gives you the lights of Petula Clark’s Downtown in your pocket.

Scratch a little deeper and you become a power user. You’ve adapted your life  to interlace with modern design, which these days means GUI (graphical user interface), haptics (touchable responses), and how to make all your gadgets talk to each other. Fluency is regarded as expertise.

There are many more layers to this than there is to steel production. Even the engineers who use Qualcomm prototyping kits aren’t cognizant of FINFET fabrication or LSI design rules.  Where is the center, the high-status-visible symbol of power, wealth, and control?

Formerly, it was the  mainframe computer, synonymous in popular view with IBM, not incidentally a potent symbol to some of U.S. world domination, which were subject to stringent export controls. But all material symbols of value, be they coin, steel, or tech, suffer remorseless deprecation and replacement.

Is there now a penultimate machine that binds together the increasingly immaterial world? Though nothing can replace the centrality of an IBM 360, there are devices that approach this. In place of “installations”, we have the Internet, the network-of-all-things, with an enormous, yet almost invisible physical presence, confined largely to windowless buildings in low-rent locations, seldom seen except by cadres of admins and repair.

Most readers have heard of servers, contained in the vast rows of racks in windowless “farms.” To these we entrust our wealth, knowledge, voices and likenesses. They are styled as vaults, yet easily breached.  China’s hackers have carried much of it off, entire factories,  in the forms of weightless, replicable plans and specs.

Servers, to which the term 5G does not apply,  have global reach, but lack global responsibility. For this, we must look at the routers, the switchboards of the network.

The penultimate machine is the core router. Some pics here. They are impressive, the largest, most complex unitary machines in the Network of All Things. Whoever owns them, by either purchase or hack, owns the Network. By extension, this includes users like you and me.

China has owned us before. (Ars Technica) Strange snafu misroutes domestic US Internet traffic through China Telecom. There is rumor (citation missing) of a much earlier hack, perhaps 20 years ago, to answer a basic question: Who in the U.S. was talking to who? For seven minutes, so the story goes, all U.S. emails were routed through China. This was accomplished by DNS poisoning.

What does this have to with 5G? Perhaps you still have the vague notion that once your voice reaches a cell tower, it travels on a wire. This is false. It travels, with some privilege, as packets of computer data on the same physical network that carries the Internet. With 5G, that fusion will become total.

The same routers that enable 5G enable  backdoor access by the makers, and by extension, the Chinese government. This cannot be mitigated, for reasons discussed in UK Think They Can Mitigate Huawei Risks.

Most of the technological lead of the West, and the democracies, has already been plundered. This time we have an advantage:  the barn door is not quite open, so 5G does not offer the requisite cautionary tale. The past is full of examples.   In 2008, a China firm acquired British IGBT maker Dynex for a pittance. I cringed at the time. (London Times) Has China used British technology to build a railgun?

Yes, they did.  Eleven years later,  that pittance bit us in the ass. The IGBT is a type of power transistor that enables energy weapons of all sorts. The cost of  countering a military that approaches qualitative parity with the U.S. cannot be measured in billions, if at all.