COVID19 update, May 22, 2020: the human immune system; unlocked but the sky isn’t falling; professional courtesy; remdesivir study update

Derek Lowe wonders if there may be a unique COVID19 immune response. In the process, he gives a nice overview of the human immune system.

The NIH discontinued its double-blind remdesivir study. Mind you, not because the drug isn’t working, but because it is working substantially better than placebo controls, and they concluded that it was unethical to continue to feed patients placebos when they had a (somewhat) working drug on hand. Related.

Attacking  COVID19 from every angle, including molecular modeling on large-scale high-performance computing facilities.

Certain media outlets that cannot bring themselves to empathize with small business workers and owners who see their income dwindle to zero can somehow wax tearful about the plight of “sex workers” during the pandemic. Instapundit snarks:

“THE PRESS HAS SYMPATHY FOR SOME PEOPLE WHO ARE OUT OF WORK: The Fragile Existence of Sex Workers During the Pandemic. Sympathy for prostitutes, though, is probably just a species of professional courtesy.”

President Trump says he won’t close the country again if a second wave of coronavirus hits. Actually, this is probably sensible. The first closure was done in a “fog of war” situation. Now we understand a bit more about the epidemic and especially about what it is not

A study by a JP Morgan analyst reportedly shows that COVID-19 infection rates are declining in states that lifted lockdowns. I haven’t seen the original, but Georgia and Florida have been open for a while now and the sky hasn’t fallen on them. (Did it move sideways? Porcupine Tree fans can’t help asking.) 

 

But as a sanity check, here is a list of countries in Europe and the Middle East that have started opening a while ago and still (click on the names for Worldometer links) have nicely trending-down active case numbers:

 

ADDENDUM: Mike Hansen MD on vitamin D

 

 

 

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”.

COVID19 update, April 24, 2020: Belgium reopening May 4, Israel reopens “phase 1.5”, NYC immunity testing, nicotine

(1) Belgium has been nibbling around the edges of its existing lockdown, allowing phone stores, garden stores, etc. to reopen, but (with the highest per capita COVID19 mortality of any country in the world) experts kept saying they were not out of the woods yet. Now the country’s national security council decided on reopening in two phases, May 4 and May 19. https://www.standaard.be/cnt/dmf20200423_04932921

In Phase 1 (May 4), the following will again be permitted:

  • outdoor sports like tennis, angling, horseback riding (as a family, or in pairs — not yet in group)
  • registered sports teams can resume training
  • public parks etc are reopened
  • car dealers/garages, bike shops, real estate offices may function “by appointment” (not yet walk-in)
  • smaller home improvement shops (paint, tiles, lighting fixtures, kitchen stores,…) may reopen
  • non-essential enterprises may resume activity, subject to social distancing
  • masks will be mandatory on public transit. (Belgium has an extensive multimodal network.)

Phase 2 (May 18) adds:

  • all remaining businesses may reopen. Hairdressers have to wear masks
  • schools gradually reopen
  • museums reopen for individuals or families, not yet for groups
  • meetings up to 50 permitted
  • visit to vacation homes (in practice, on the sea coast or in the Ardennes): details to be finalized

“Horeca” (hotels, restaurants, and cafés) are not to be opened before June 8.

(2) Israel was supposed to have its Phase 2 reopening in a week, but apparently decided to speed things along a bit. As of Sunday, remaining stores are allowed to reopen. In addition, hairdressers are allowed to reopen, with maximum 2 clients at a time, and disinfecting equipment between every haircut. Indoor malls still remain closed for now. Restaurants, which until now were only allowed to operate by delivery, are now also permitted to offer takeaway (not yet with seating).

The country will go in hard lockdown over Memorial Day and Independence Day, to prevent super-spreader events like there were at Purim, but that should be “it” for a while. Active COVID19 cases in Israel have been declining for a week now, as recoveries outpace new cases.

(3) Much ado about preliminary results from a community testing effort in NYC that appears to indicate as much as 20% of the NYC population has antibodies for COVID19. (The figure drops to 3.6% for upstate New York.)

(4) (Hat tip: Erik Wingren.) Peculiar and counterintuitive claims (see here and here) from France that smoking, and specifically nicotine, would have a protective effect — specifically, that the COVID19 patient populations contained an anomalously low percentage of smokers compared to the general population.

A French study from the Université Pierre et Marie Curie found that just 8.5 percent of 11,000 hospitalized coronavirus patients were smokers compared to 25.4 percent of the country’s population.

They are now experimenting with nicotine[*] patches. The initial data from China (caveat emptor) appeared to indicate that smoking was a risk factor because of damage to the lungs — but that damage comes overwhelmingly from tar, not from nicotine. (I wonder if anybody looked at “vapers” for comparison?) Anecdotally, a friend who is immunocompromised following an organ transplant, and has been having regular troubles with bronchitis, told me he took up vaping (which gives him nicotine but not tar), and it greatly reduced his respiratory issues.

[*] What is the purpose of nicotine in nature? Some plants produce alkaloids to deter animals from eating them: for this purpose, tobacco produces nicotine (named after Jean Nicot, the 16th century French diplomat who was the first to bring tobacco to France).

COVID19 update, April 16, 2020: Germany’s exit roadmap; brief Belgium update; UPDATE: Switzerland’s time table

A light edition today, as I’ve returned to work post-Passover.

Germany appears to have passed the peak of the infection, and for several days running now has seen recoveries exceed new infections.


Consequently, the number of active cases is dropping:

Austria is about a week further along on this trajectory, and started reopening yesterday. Now the German Chancellor, Angela Merkel, has announced a roadmap for Germany’s return to normality yesterday, Some key points translated from the German “breaking news” report (and from the original document, see below):

  • Stores smaller than 800 m2 (about 8,800 sq.ft.) will be allowed to reopen Monday April 20, with hygiene and distancing measures. The motivation appears to have been to exclude indoor malls and stores that functionally operate as such from the initial opening permit.
  • In addition, bike stores, automobile dealerships, and bookstores can reopen on the same day regardless of floor area.
  • Also allowed to open on the same day are zoos, public parks, botanical gardens, and libraries.
  • Schools will gradually reopen May 4, beginning not with the youngest (as Israel is considering), but with classes in their final exam years, as well as the final grade of elementary school.
  • hairdressers and cosmeticists can reopen May 4 (with protection)
  • mass public events such as concerts, festivals, soccer matches, etc. will remain banned until August 31.
  • the Free State of Bavaria/Bayern will wait an additional week beyond these deadlines, as it was particularly hard-hit. In general, the Länder (lands, constituent states of the Federal Republic) will have leeway in working out details.
  • industrial activity is to carry on as normally as possible, under observance of social distancing, and telecommuting where at all feasible. In sectors where standstills have occurred due to lacking supply of components or spare parts from abroad, the government is to step in to help secure these
  • agriculture, it seems, was never restricted in any way (thank G-d)
  • masks are strongly recommended for any situation where it is impossible to keep a distance of at least 1.5m (5ft), e.g., on public transit
  • people are strongly urged to avoid all unnecessary travel within the country. Travelers abroad are still subject to a 2-week quarantine upon return, with exceptions for those transporting goods (e.g., truck drivers) and for cross-border commuters in border areas.
  • hotels and travel services can resume limited activity for necessary travel, not for leisure tourism

Note that the original report in DIE WELT was (understandably, given the “hot” breaking news character) written in great haste, and contained a capital mistake concerning religious services, implying that they would remain prohibited indefinitely. Predictably, this led to considerable commotion both in Germany and abroad.

However, here is the full document from the Bundesregierung (Federal Government), which instead says:

The Federal Chancellor and the heads of government of the Länder [i.e., the semi-autonomous “lands”/member states/top-level provinces that made up the Federal Republic] are aware that the practice of religion is a particularly valuable asset and, especially against the background of the difficulties that this epidemic and its consequences are causing for many people, living faith gives strength and confidence. However, after all we know about the role of meetings in the spread of the virus and about the risk of infection and the serious consequences for vulnerable groups [read between the lines: attendance at places of worship is heavily skewed to older people], it is still urgently necessary to limit ourselves to the transmission of religious content through the media. Meetings in churches, mosques, synagogues as well as religious ceremonies and events and the meetings of other religious communities should not take place for the time being. The Federal Ministry of the Interior, Building and Homeland Affairs, together with representatives of the Prime Minister’s circle, will begin talks with the major religious communities this week in order to discuss a way forward that is as consensual as possible.

In other words: I expect places of worship to reopen, with distancing restrictions (in practice: a cap on attendance), sometime in May unless an agreement can be reached very quickly. Lest anybody doubt the role of religious ceremonies in spreading an infection like this: Israel had major “super-spreading” events during Purim celebrations and closed down all communal houses of prayer (synagogues included) for the duration. What’s more: two ultra-Orthodox communities where rabbis at first continued to operate synagogues and yeshivot (communal religious academies) in defiance of the order now account for about 40% of all COVID19 cases in Israel. The virus doesn’t care whether you’ve come to pray, to watch a soccer match, or to hear Dream Theater play their new album — from its perspective, they are all large crowds of people packed together.

The same full document also stresses what I call TTT (test, track, trace) as a cornerstone of the strategy. Present testing capacity is stated as 350,000 a week. (Germany avoided the mistake of the CDC and decentralized testing from the start, with individual Länder harnessing the private sector.)

Meanwhile in next-door Belgium, a similar “roadmap” is being worked on but has yet been published. Instead, existing restrictions are being trimmed ad hoc at the margins. For example, about a week ago cell phone and telecommunications stores were added to the “permitted essential businesses” list, and both garden supplies stores and DIY stores are now allowed to reopen.

UPDATE: Switzerland is reopening April 27 (except for Ticino/Tessin canton bordering on Italy, which got it bad and will follow later). The Neue Züricher Zeitung has details (in German): https://www.nzz.ch/…/corona-ausstiegsstrategie-der…

Briefly:
27 April: Garden centers, flower shops, DIY shops, etc…. also with hygienic measures: hairdressers, massage, beauty salons.
11 May: remaining stores
8 June: middle schools, vocational schools, high schools, zoos, museums.
TBD: restaurants (Swiss don’t eat out as much as Americans in urban areas tend to do, BTW), touristic infrastructure, recreational facilities like swimming pools.

COVID19 update, April 9, 2020: Passover quick takes

Happy Passover to my Jewish readers! Some quick takes on the holiday:

(1) Germany’s Minister of Health Jens Spahn is looking at reopening the country, reports DIE WELT (in German). He sees two main preconditions: (a) numbers keep evolving in the right direction; (b) businesses will be compliant with hygiene and distance requirements 

Spahn on video: “The Easter Weekend will be a fork in the road.” Paraphrasing: If we remain compliant, we may soon be on the road to renormalization. If we become lax and complacent, we may be stuck with this for a long time.

DIE WELT also reports that Chancellor Angela Merkel is reluctant to open early, as she is afraid that a flare-up following a hasty reopening will instead lead to a much longer shutdown

(2) A European Union think tank is drafting a “European roadmap for an exit from the COVID-19 epidemic” , and Die Welt obtained a copy. Their recommendations echo some of what the German decision makers are mulling, but urge a coordinated response of all European countries. At the same time, they recommend that specific lockdown relaxation decisions be taken at a local (district or province, not national) level — such that if a flare-up does occur, the affected district can be separately placed in renewed lockdown, rather than the entire country.

Also, enough time should be left between relaxation steps to assess their impact. 

Fundamentally, blanket “one size fits all” measures should give way to targeted measures

(3) De Standaard (in Dutch) reports hopeful signs from Belgium where total COVID19 hospitalization keeps dropping. 

(4) Via Instapundit, a peculiar result from a French cancer research team, where of a group of 2,500 high-risk cancer patients that were administered the antioxidant methylene blue as part of their therapy (for reasons unrelated to COVID19), allegedly not a single patient got infected by COVID19. The researchers hypothesize that the changes in cellular pH induced by methylene blue impede the replication of the virus, in the same manner as they hypothesize (hydroxy)chloroquine work

This particular institute seems to be exploring the controversial theory of Otto Warburg (Nobel Prize in Medicine 1931 for “discovery of the nature and mode of action of the respiratory enzyme”)  that cancer is primarily a metabolic disease. (Mainstream oncology considers the metabolic peculiarities of cancer cells an effect, rather than a cause.)

(5) Some New York physicians, who look at the terrifying death rate among adults placed on “ventilators” (read: lung intubation), now favor keeping patients off invasive respiration as long as possible, as they suspect that long-term intubation is itself a stressor.

(6) CDC director Robert Redfield says actual mortality will be much lower than models predicted.

(7) As Zoom has become so popular during this epidemic, and contains a number of cyber vulnerabilities, here are some cyber security recommendations from CheckPoint Software 

(8) Roger Seheult MD, host of the YouTube channel MedCram, has an update on ivermectin and COVID-19 that makes its possible mechanism quite clear to people other than molecular biologists.