COVID19 update, May 19, 2020: scaling up drug production; super-spreading events; reopening churches and synagogues; Matt Ridley on vitamin D

(1) OK, so you have an experimental coronavirus drug and suppose it actually works — what next? NATURE has an article on the challenges involved in scaling up production to massive quantities. For instance, Gilead, having donated its entire supply of drug on hand, has now licensed production to five generics manufacturers.
And like with other manufactured products, the switch to “lean” “just in time” manufacturing and the outsourcing of critical components to cheap specialized suppliers abroad creates vulnerabilities. (The article gives a non-Chinese example: following the Fukushima earthquake and tsunami, the pharmaceutical industry faced a shortage of polyethylene glycol, as all major suppliers of this chemical were in Japan.)

(2) According to an analysis by the London School for Hygiene and Tropical Medicine, super-spreader events may be responsible for 80 percent of more of COVID19 cases, reports The Daily Telegraph.

“As most infected individuals do not contribute to the expansion of an epidemic, the effective reproduction number could be drastically reduced by preventing relatively rare superspreading events”[…] Hospitals, nursing homes, large dormitories, food processing plan[t]s and food markets have all been associated with major outbreaks of Covid-19.

Vigorous physical activity in an indoor space without adequate ventilation is one risk factor, as a South Korean analysis of outbreaks at intense workout classes at gyms found. Less strenuous classes, such as yoga, were not associated with such outbreaks, nor were outdoor sports.

Singing at high volume, and the attendant voice projection[*], is another factor associated with super-spreading events:

In Washington State on the west coast of America, a church choir went ahead with its weekly rehearsal in early March even as Covid-19 was sweeping through Seattle, an hour to the south. Dozens of its members went on to catch the virus and two died. [par] The Washington singers were not the only choristers to be hit. Fifty members of the Berlin Cathedral Choir contracted the virus after a March rehearsal, and in England many members of the Voices of Yorkshire choir came down with a Covid-like disease earlier this year. [par] A choir in Amsterdam also fell victim to the virus, with 102 of its 130 members becoming infected after a performance. One died, as did three of the chorister’s partners.

I’ve already mentioned carnival celebrations in Germany, with everybody kissing everybody and hollering at each other in packed beer halls to be understood over the loud ‘music’. (Outdoor beer gardens are probably safe, if you don’t share steins.) And then there are the apres-ski parties that have become a by-word:

Hundreds of infections in Germany, Iceland, Norway, Denmark and Britain have been traced back to the resort of Ischgl in the Tyrolean Alps. Many had visited the Kitzloch, a bar known for its après-ski parties. [par] The bar is tightly packed and famous for “beer pong” – a drinking game in which revellers take turns to spit the same ping-pong ball into a beer glass. [par] Earlier this year The Telegraph obtained a video from inside the Kitzloch. It may yet come to define the perfect superspreader event, with attendees all singing along to AC/DC’s Highway to Hell

Had I written the latter detail in a novel, an editor would consider it a particularly cheesy foreshadowing technique.

But here is the good news from all of the above: none of it is representative of how one goes about one’s normal daily business.

(3) Prayer without singing returns to synagogues in Germany and Israel (h/t: Mrs. Arbel). Church services in Germany actually reopened a couple of weeks ago: aside from social distancing similar to what is described below for synagogues, no singing.
I had a look at the website of the Zentralrat der Juden in Deutschland (Central Council of Jews in Germany): they actually have a section with COVID19 guidelines. My abridged translation:

* public prayer and Torah reading are allowed again
* people with even mild symptoms should stay away
* maintain a distance of 1.5m (read: 5ft), preferably 2m (6.5ft)
* it is recommended to keep attendance lists in case contacts need to be traced
* if need be to maintain distance, use the largest hall or sanctuary available rather than a small chapel (as many congregations use for regular services)
* no handshakes, hugs, kisses
* worshipers are urged to wear masks (regular day-to-day nonsurgical masks OK)
* recommended to bring your own siddur (prayer book) and, on the Sabbath, chumash (book with the Torah and commentaries)
* using only one’s personal kippa/yarmulke/skullcap and tallit/prayer shawl (and, for weekday morning minyan, tefillin/phylacteries)
* doorknobs etc. are to be disinfected frequently
* disinfectant should be on hand
* no kissing of religious objects (e.g., mezuzah, Torah scroll) — therefore, usual Torah scroll procession before the reading off the menu
* no touching the Torah scroll when called up for a reading[NB: these behaviors are customs and not Jewish law]

(4) Matt Ridley Ph.D., veteran popular science writer and editor[**], lays out the evidence on vitamin D. As usual, his writing is a paragon of clarity.

[M]any people are deficient in vitamin D, especially at the end of winter. That is because, uniquely, vitamin D is a substance manufactured by ultraviolet light falling on your skin. You can get some from fish and other foods, but not usually enough. So most people’s vitamin D levels fall to a low point in February or March when the sun has been weak and its UV output especially so. Public health bodies have long advised people to supplement vitamin D in winter anyway. The level falls especially low in people who stay indoors a lot, including the elderly, and in those who have darker skin. Whereas the safe level of vitamin D is generally agreed to be above 10 nanograms per millilitre, one recent study of South Asians living in Manchester found average levels of 5.8 in winter and 9 in summer: too low at all times of the year. Darker skin reduces the impact of sunlight; so does the cultural habit of veiling; and so does a reluctance among some Muslims to take supplements that might have pork-derived gelatin in them.Vitamin D deficiency has long been known to coincide with a greater frequency or severity of upper-respiratory tract infections, or colds. That this is a causal effect is supported by some studies showing that vitamin D supplements do reduce the risk of such infections. These studies are not without their statistical flaws, so cannot yet be regarded as certain, but they are not quackery like a lot of the stuff coming out of the supplements industry: they come from reputable medical scientists.

What about vitamin D and Covid in particular? Results are coming in from various settings and the main message seems to be that vitamin D deficiency may or may not help to prevent you catching the virus, but it does affect whether you get very ill from it. One recent study in Chicago concluded that its result ‘argues strongly for a role of vitamin D deficiency in COVID-19 risk and for expanded population-level vitamin D treatment and testing and assessment of the effects of those interventions.’ The bottom line is that an elderly, overweight, dark-skinned person living in the north of England, in March, and sheltering indoors most of the time is almost certain to be significantly vitamin D deficient. If not taking supplements, he or she should be anyway, regardless of the protective effect against the Covid virus. Given that it might be helpful against the virus, should not this advice now be shouted from the rooftops? A new article by a long list of medical experts in the BMJ cautiously agrees, confirming that many people in northern latitudes have poor vitamin D status, especially in winter or if confined indoors, and that low vitamin D status ‘may be exacerbated during this COVID-19 crisis by indoor living and reduced sun exposure’.

Read the whole thing. I’ve been taking vitamin D and zinc supplements since the beginning of the crisis, even though I live in sunny Israel and have a very light skin type.

(5) This cartoon from Die Welt probably does not require translation:

[*] full disclosure: I am married to a classical soprano. She can easily fill a hall with sound without a microphone — and one does not achieve that feat without some serious air pressure.

[**] and member of the House of Lords, as the 5th Viscount Ridley

COVID19 update, May 9, 2020: Spreading reconsidered; German pathologist and Swiss doctors identify thrombosis as #1 killer in severe COVID19, Swiss clinical trial with aggressive anticoagulation treatment; meat supply chain disruptions in Germany

(1) The Daily Telegraph has a long article about an epidemiologist at St Andrews U., Scotland, who has been analyzing a number of epidemiological “contact tracing” studies on how COVID19 spreads.

https://threadreaderapp.com/thread/1257392347010215947.html

(Quote)

An analysis of such studies was recently posted on Twitter by Dr Muge Cevik, an infectious diseases clinician and researcher from St Andrews University. It was promoted by Sir Jeremy Farrar, the head of the Wellcome Trust and a member of the Scientific Advisory Group for Emergencies (Sage). “If you read one thread,make it this one,” Sir Jeremy said.

(Twitter thread unrolled here)

Dr Cevik starts with a big Chinese study that traced 2,147 close contacts of 157 confirmed Covid-19 cases. The overall infection rate was six per cent, but it was much higher among friends (22 per cent) and family members (18 per cent). In terms of location, the main risk factors were homes (13 per cent) transport (12 per cent) and dinner and entertainment (seven per cent).

Broadly similar findings emerge in several other papers. Risk of infection is much higher within households or other enclosed environments in which contact is close and sustained. In the outdoors, it falls to something in the 0-5 per cent range.

[…]A Chinese study of 392 contacts of 105 confirmed cases found that the attack rate in children was just four per cent within the home, compared with 17.1 per cent in adults, for example. The infection of spouses was super high, at 28 per cent. 

Emphasising the link with age, another study found that household members over 60 were much more likely to become infected (18 per cent) than those under 20 (five per cent).

Children, it seems, are not only better able to resist the infection within the home but also less likely to bring it back with them. A study, funded by the Australian Research Council, of 31 household clusters including children found that only 10 per cent had been sparked by children.

Using these and other studies, Dr Cevik concludes that they suggest (not prove) the following:

[emphases mine in the quote below]
  • Close and prolonged contact is required for transmission of the virus. 
  • Risk is highest in enclosed environments such as houses, care facilities, public transport, bars and other indoor spaces where people congregate.
  • Casual, short interactions are not the main driver of the epidemic. 
  • Susceptibility to infection increases with age.

(2) Die Welt has a video interview (in German) with Prof. Nils Kucher at the Zurich university hospital. 

Summarizing his remarks:

  • We got severe COVID19 completely wrong in the past. This is changing as overwhelming evidence accumulates, e.g. from autopsies, and is published
  • Severe COVID19 is not a conventional viral disease at all, but a coagulation disease
  • Endothelial cells have ACE2 receptors. The virus docks there, cause inflammation of the endothelium, this leads to release of cytokines. (Cf. “cytokine release syndrome”, a.k.a. “cytokine storm”.) Thrombosis ensues, and eventually the patient dies of embolisms
  • It has taken us way too long to figure that out, which has cost needless lives
  • The way to prevent thrombosis is treatment with [?]molecular weight heparin. Guidelines traditionally limit this to hospital settings because of the risk of hemorrhage 
  • Often patients seem to be in decent shape, are sent to home isolation with just antifebriles, and then some die of thrombotic events
  • Now we [=Zurich U. Hospital] are running a clinical trial on 1,000 ambulatory COVID19 patients. Half get standard care, the other half also get heparin injections. All are closely monitored by telephone in case something goes awry. For the heparin treatment with that patient group, the risk of hemorrhage is rated as less than 1%
  • Sadly, doing a control group creates an ethical problem if it’s a deadly disease and you are pretty sure you have the answer

Related: a Hamburg coroner, Dr. Klaus Püschel , talks about what he has learned from 192 autopsies on COVID19 patients (Under a law in the Free City of Hamburg, autopsies are mandatory for deaths from an infectious disease.)

“Of the first dozen I autopsied, seven died of thrombose, four directly of lung embolisms.” 

Those results were just published [following peer review by four experts, which takes a while] in the Annals of Internal Medicine. http://doi.org/10.7326/M20-2003

Independently of his colleague in Zurich, Hamburg University Hospital Prof. Stefan Kluge wonders if treatment of severe COVID19 patients should not primarily feature anticoagulant therapy.

[My “gut” tells me: a combination of anticoagulants and immunomodulators.]

Coroner Klaus Püschel : “This isn’t a killer virus, we’re not at war. We must not fear and should not give up.”

(3) Now even De Standaard (in Dutch) has woken up to the problem of food insecurity in the US. The article is a mixed bag: the journalist is clearly  floored by the generosity of Americans (in “nanny states” like Belgium, there is a tendency on the part of people to say, “oh, helping people, that’s the government’s job”). At the same time gets taken in by socialist snake oil peddled by the likes of “Beta” O’Rourke.

(4) On a related note, supply chain disturbances for meat are not just a US phenomenon: Here are two articles telling of outbreaks at two meat processing plants, one in Schleswig-Holstein in the North, the other in Baden-Württemberg in the South.

Consequently, meat prices are rising in Germany.

COVID19 update, April 27, 2020: Israel and Europe progress; worrisome signs in the US food supply chain; Bastiat and “non-urgent” healthcare

(1) Let’s have a quick roundup of the latest active cases data from worldometers (I’ll leave Israel to the last):

Germany’s active cases 39,794 are down to 55% of the peak value on April 4, 72,865. Switzerland is doing better still — 5,651 down from a peak of 14349 on March 31, or down to 39% of peak. Austria stands at 2,401, or down to 26% of its April 3 peak of 9,334. Norway’s graph has no info on recoveries (hence no useful info on active cases), but daily new cases are a fraction of their peak. Total dead are clearly nearing the top of the sigmoid at 201. Finland’s graph looks like a wild zigzag owing to intermittent reporting of recoveries — but seems to be trending the right way. Active case graphs in Spain, Italy, and France seem to indicate these countries are turning the corner — if they can prevent a second flare-up.

Belgium, however, is not out of the woods yet, nor are the Netherlands and the UK. Sweden looks murky, with active case numbers still climbing about linearly, but total deaths seemingly starting to level off. The US — overall looks pretty grim still, but if greater New York City were taking out of the equation, the rest of the country looks rather rosier.

As for Israel: our active cases have been dropping steadily since April 15, from a high of 9,808 to the present 8,511. Recoveries have exceeded new cases since April 16. The total number of dead has crossed the 200 mark, but the curve over time shows a clear sigmoid that appears to be close to leveling off. With 15,443 documented infections since the beginning of the crisis (of which 6,731 documented recoveries), our apparent “case fatality rate”, at 201/15,443*100% = 1.3%. However, keep in mind that Israel counts everybody who tests positive, whether they develop symptoms or not. Guesstimating about half of these to be asymptomatic, the true CFR may be closer to double that, while the true IFR (infection fatality rate) is certainly lower than 1.3%, as despite increased testing capability the country is sure to have a significant Dunkelziffer/stealth infection rate. (Do keep in mind Israel has a much younger population pyramid than the major developed countries — this alone accounts for our low number of severe cases. The stories of young and healthy people without pre-existing conditions getting severe COVID19 are “man bites dog” news, not significant shares of the patient population.)

Israel indeed has done something today that I can only hope the US is wise to do soonest: opened its hospitals and HMO policlinics for elective procedures. (A lot of “gray area” care is technically elective in that it doesn’t have to happen right this second — but any unnecessary delay will cause complications later.)

Finally, in India lockdown is to end May 3, but it’s getting rolled back already in some less-stricken locations.

(2) Rather more worrisome news from the US, with twin posts (here and here) reporting about food supply chain disruptions from the agricultural side of things. I reached out to a few people informed about goings-on, and the problems are basically threefold:

  • Choke points in the distribution chain were created by COVID19 outbreaks at meat processing plants (like Smithfield’s in South Dakota), which necessitated closure, sanitation, and reopening at reduced capacity. (At some processing plants, workers are also reluctant to show up.) Hence, farmers are stuck with hogs etc. and no place to have them processed.
  • Farmers whose chief outlet was to the large food service companies and institutional customers are now stuck with product they cannot unload, except at a loss. Their operational cash headroom is limited at the best of times;
  • Meanwhile, those who supply to the grocery chains see shifting demand. Dairy, for instance, is down. This has caused prices paid to farmers to drop to “below cost” levels.

There are second-order effects: corn growers who primarily supply pig farmers etc… And with oil prices down to historical lows, selling corn for ethanol is not practical. (Incidentally, while some farmer supplies (e.g., fuel) are cheaper, others go up in price because imported from, you guessed it…)

I doubt dire predictions of famine in the USA will come to pass (and dearly hope and pray they won’t). However, remember the USA is a major food exporter — and that it is likely to apply the maxim “the poor of my own city come first” in a serious food crisis. So major shortages in countries that are dependent on US food imports are increasingly likely. 

“Just-in-time” supply chains can normally respond smoothly to ordinary shifts in demand, and thus keep prices down for the end consumer. However, they are fragile to major disruptive events like COVID19. The old engineer’s maxim “better, cheaper, faster — pick any two” seems to have a supply chain counterpart: “cheap, just in time, robust: pick any two”. 

The social distancing measures in the USA (outside greater NYC,  and perhaps a few other congested metropolitan areas) have crossed the line from diminishing returns territory into doing more damage than they prevent — it is high time to return no normality. Scott Atlas MD definitely agrees.

(3) On a final note: Dr. Paul Hsieh quotes Bastiat about “the seen vs. the unseen [costs]” in the context of emergency care. (Bastiat’s classic essay expounding the concept of hidden costs and consequences should be required reading, not just for any economics student, but for every public servant and every elected official.) The number of COVID-19 deaths are in the public eye. The number of people dying from cardiac complications or ruptured appendicitis because they were unwilling to come to the ER for fear of contracting COVID19 (a phenomenon seen in Europe as well as the US) are not so obvious — but they are still there. This is without going into the urgency level one step below: cancer surgeries, non-emergency bypass surgeries,…

UPDATE: John Tyson, chairman of the board of Tyson Foods, weighs in on the company’s blog: “Feeding the nation and keeping our employees healthy”.

UPDATE 2: more about the MIT study on the NYC subway as “the mother of all super-spreader events”.