COVID19 update, March 31, 2020: a brief look at Belgium

Belgium, historically a crossroads between rival European powers, now is home to the European Union’s nerve center in Brussels. I have been following De Standaard (in Dutch) for updates on the situation there.
This article quotes virologust Steven De Gucht. A few bullet points:

  • 485 new hospital admissions in the past 24 hours
  • 94 new fatalities, but this included deaths since March 11 from care centers for the elderly that had not percolated through the reporting yet (all above age 65). Total mortality is 705, of whom 93 percent are over age 65
  • the youngest victim yet is a thus far unique case of a 12-year old girl. Her status deteriorated suddenly after 3 days of fever. [Cytokine storm?!] De Gucht calls for investigating this rare and anomalous case in detail
  • 876 new cases, the second drop in a row
  • hospital admissions, at 485, are likewise down for the 2nd time. Total COVID19 hospital population is 4,920 — that number keeps mounting as COVID19 patients tend to be in for long hospital stays. 168 patients were discharged today.
  • 1,021 patients total are in intensive care (an increase by 94).
  • 786 patients need respiratory assistance of some sorts
  • 20 are on ECMO (“heart-lung machines”)
  • the article is accompanied by the following infographic:
green=new hospital admissions, teal=ICU, red=deceased

Elsewhere today, the same paper quotes medical sources as saying, “we’re off the Italian track, but not yet onto the Scandinavian one” . The subtitle says, “wait another few days to see if we’re really past the peak”.

And in what sounds like a bold bet, Johnson & Johnson, parent of local Janssen Pharmaceutica NV,  is planning to take a vaccine into production even while the clinical trial is running. It expects to be up to full production early next year. The article quotes Johan van Hoof, director of the vaccines division of Janssen, as saying “Theoretically this could go wrong. But we have enough experience with vaccines to be very optimistic. This virus uses the same ‘key’ [i.e., the so-called “spike protein] to penetrate the lungs as SARS did. So we know we can protect people if we can make the right antibodies be produced by the body.” [A DNA vaccine for the original SARS that expressed the spike protein never saw wide application in humans as the epidemic died out first.]

UPDATE: this isn’t Belgium, but in New York, Rabbi Daniel Nevins, dean of the Jewish Theological Seminary, who recovered from a mild case of COVID-19 earlier this month, is now donating plasma for an antibody therapy trial. https://www.jpost.com/Diaspora/Rabbinical-school-dean-participates-in-experimental-coronavirus-treatment-622670

COVID19 update, March 30, 2020: the quest for a vaccine, high-throughput testing

(1) Mrs. Arbel forwarded a long article that peeks inside the frantic efforts to develop a vaccine. An archived copy is here. Basically, the first step, coming up with a candidate vaccine, has been drastically shortened thanks to modern advances in biotech, genomics, and proteomics. What still takes almost as much time as it used to is testing in healthy subjects:

(2) Mako N12 (Hebrew news site) has an article on a novel high-throughput testing assembly developed by two PIs at the Weizmann Institute in Israel, in collaboration with two academic hospitals, Tel HaShomer in Ramat-Gan (one of the five Tel-Aviv boroughs) and Assuta Ashdod. The system can process up to 384 samples at a time, for a maximum throughput of 20,000 tests per day. Aside from automation and “massive parallelization”, one innovation is that the samples are dropped immediately into a kind-of “fixation” solution, which renders them biologically harmless. This eliminates the need for elaborate biocontainment facilities. Apparently the facility is going through final approval procedures.

(3) “masgramondou” brought this article by Dr. John Lee in The Spectator to my attention: https://spectator.us/understand-report-figures-covid-deaths/ on why the CFR (case fatality rate) statistics differ so widely. This affects both the numerator (do you count everybody who dies from any cause while COVID19-positive, or do you only count if COVID19 is definitely the cause of death) and the denominator (do you test aggressively, or do you only bother testing when it’s already pretty sure the person is ill).

(4) Speaking of statistics and comparing apples to apples: I remember this morning Mrs. Arbel gasping at a report in the Jerusalem Post that such a large percentage of the Israeli patients are between 20 and 30 years old. However, this is not entirely surprising once you compare Israel’s population pyramid with that of, say, Italy:

Another factor, which Mrs. Arbel pointed out, is the widespread custom of long post-army treks. The tendency of our young people to congregate in tightly packed quarters and in general not to keep people at a safe arm’s length adds to the ease with which an infection can spread.
The comparatively young profile of our general patient population is reflected in the low percentage (below 2%) of critical cases: As of today, 4,347 Israelis have been diagnosed, but only 80 people in serious condition (including one 20-year old man) of whom 63 patients requiring ventilation. 16 people have died. About half the diagnosed people appear to be asymptomatic (for now).
The age profile of critical patients is much the same as everywhere else: older people with pre-existing health conditions (referred to in Hebrew as machalot req`a , literally “background diseases”), or very old people.

UPDATE: FDA gives emergency approval for chloroquine and hydroxychloroquine for COVID19

COVID19 update, March 29, 2020: two brief items+new French hydroxychloroquine study

Day job (remotely) absorbed my day, so today I only have two brief items

(1) (H/t: a friend): Systems biologist, Prof. Ron Milo from the Weizmann Institute has released coronavirus by the numbers, with nearly daily updates. The “numbers” are accompanied by explanatory text written in a way that non-biologists can follow it — not “obscured by clouds” of jargon.

(2) I had an online conversation with a leading neuroscientist about our response to stress in such a situation. In a nutshell: our stress response system is optimized for a very different scenario: a lion or pack of wolves coming after you. Heart rate and blood pressure going up, blood sugar and cortisol levels… all great if you need your running speed and reflexes boosted to escape from a predator.

The trouble is with more diffuse, long-term threats like a COVID19 epidemic leading to “chronic stress”. The results is anxiety, sleep deprivation, depressed immune response, … He suggested meditation [his response when I suggested old-school Jewish prayer instead was rather bemused ;)], exercise (even in the house if confined there, outdoors if possible), and any sort of enrichment activity that you derive joy from.
At my observation that obsessive news readers may simply have to “ration” the news updates, since it’s possible to be distracted 24/7 by them and kept in a permanent state of anxiety, the neuroscientist nodded.

(3) Via Instapundit: The same French team at the Mediterranean Institute for Infectious Diseases in Marseille, which reported an initial pilot clinical trial with an hydroxyquinoline-azithromycin combo now has a larger study out:

In 80 in-patients receiving a combination of hydroxychloroquine and azithromycin, the team found a clinical improvement in all but one 86 year-old patient who died, and one 74-year old patient still in intensive care unit. The team also found that, by administering hydroxychloroquine combined with azithromycin, they were able to observe an improvement in all cases, except in one patient who arrived with an advanced form, who was over the age of 86, and in whom the evolution was irreversible, according to a new paper published today in IHU Méditerranée Infection.

“For all other patients in the cohort of 80 people, the combination of hydroxychloroquine and azithromycin resulted in a clinical improvement that appeared significant when compared to the natural evolution in patients with a definite outcome, as described in the literature. In a cohort of 191 Chinese inpatients, of whom 95% received antibiotics and 21% received an association of lopinavir and ritonavir, the median duration of fever was 12 days and that of cough 19 days in survivors, with a 28% case-fatality rate (18),” the research team said.

The team went on to say: “Thus, in addition to its direct therapeutic role, this association can play a role in controlling the disease epidemic by limiting the duration of virus shedding, which can last for several weeks in the absence of specific treatment. In our Institute, which contains 75 individual rooms for treating highly contagious patients, we currently have a turnover rate of 1/3 which allows us to receive a large number of these contagious patients with early discharge. Chloroquine and hydroxychloroquine are extremely well-known drugs which have already been prescribed to billions of people.”

“In conclusion, we confirm the efficacy of hydroxychloroquine associated with azithromycin in the treatment of COVID-19 and its potential effectiveness in the early impairment of contagiousness. Given the urgent therapeutic need to manage this disease with effective and safe drugs and given the negligible cost of both hydroxychloroquine and azithromycin, we believe that other teams should urgently evaluate this therapeutic strategy both to avoid the spread of the disease and to treat patients before severe irreversible respiratory complications take hold,” the team concluded.

Preprint online at https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-IHU-2-1.pdf

Related, Carmi Sheffer, an Israeli doctor working in Italy shares some experiences in the Times Of Israel.

In Padua, the autoimmune medicine Tocilizumab has proven effective, but can only be used once it is established that no other viruses or bacteria are present in the patients’ bodies, he said. The hospital where he works has also seen positive results from the antiviral drug Remdesivir, he added.

[…] One technique he said had yielded dramatic results was to have patients lie on their stomach instead of on their back while on a ventilator. “Suddenly the oxygen level in the blood jumped [up],” he said.

[A source in Belgium told me they had started doing this as well.]

Dr. Sheffer believes, “I think the worst is behind us. We will control the virus and flatten the curve within a few weeks, but the closure will continue until June,” he predicted. 

COVID19 update, March 28, 2020: South Korea’s experience in more detail

Stephen Park, who runs the YouTube channel “Asian Boss”, managed to secure an interview with Dr. Kim Woo-Ju of the Transgovernmental Enterprise for Pandemic Influenza in Korea. How did the country manage to nip the epidemic in the bud, so to speak? Or, using a different metaphor (see below), skip the “hammer” phase and move straight to the “dance” phase?
https://medium.com/@tomaspueyo/coronavirus-the-hammer-and-the-dance-be9337092b56

Here is the full video (in Korean with English subtitles) follows at the end of the post (due to a WordPress glitch). The URL is:
https://www.youtube.com/watch?v=gAk7aX5hksU

Below follow my notes from the video:

* Koreans learned from 2009 H1N1 swine flu and 2015 MERS outbreak
Mask discipline, rapid PCR testing capability. Massive investment in R&D of PCR kits
* * MERS: 186 patients, 38 dead. Only country outside Middle East that had an outbreak
* status as of March 24 in South Korea: 8.961 cases, of which 20% asymptomatic. 111 dead.
Case fatality rate by age:
11.6% over 80
6.3% in seventies
1.5% in sixties
0.4% in fifties
0.1% in thirties and forties [but stats of small numbers, since only one fatality of each]
no fatalities (yet) below 40
* reason for age dependence: (a) immunosenescence, natural decay of immune system with age; (b) pre-existing conditions [that become more frequent with age]
* reactivation cases: have seen some cases that were discharged as cured, then came back 5-7 days later
* in South Korea, anyone can get tested on demand for pay: if found positive, gov’t refunds test. Should get tested if feel any of sore throat, fatigue, fever,…
* masks ARE definitely useful, though should go to healthcare personnel in 1st priority[, general public in 2nd priority]. Proved their worth during SARS and MERS outbreaks. Eyeglasses are useful! Infection occurs through mucous membranes (mouth, inside nose, eyes): virus needs ACE2 receptors, none to be had on epidermis of regular skin.
* main vectors: 1st: droplets from cough, sneeze on mucous membranes (can travel up to 2m in Earth’s gravity field); 2nd hands after wiping nose; 3rd droplets falling on keyboard, table,…
* risky locations: isolated gathering places, e.g. places of worship (he hinted at shouting preacher reaching further than 2m)
* presently, 20% of new cases arrive at airport from aborad. Everybody is now tested on arrival, held overnight at a temporary facility. Turnaround time for PCR testing is 6h, but can be overnight due to overload. If found positive, sent to hospital if moderate or severe symptoms, to special treatment clinic for mild cases. If found negative, tracking app installed on cell phone and sent to 14-day (?) home quarantine
* from 20 March, strongly recommended to close bars, churches, gyms, clubs (in “Gangnam” district), and cram schools (after-school college admission prep schools) for 2 weeks. Least successful with cram schools: 90% still open
* How long does he think this will last? Best-case scenario would be like SARS. (November 2002 outbreak killed 776 people out of about 8000 worldwide, fatality rate of 9.6%. Then just… disappeared basically). If all countries work together to whip this, could be gone by July-August; 2nd scenario: sputters out in Northern hemisphere in summer and but flares up “Down Under” during their winter, then comes back to North during winter, and becomes part of seasonal infection cycle; 3rd scenario: develop a vaccine and vaccinate the whole human races. If all goes well, should have vaccine in 18 months.
* drug repurposing: gives Viagra as best-known example. Originally developed for pulmonary arterial hypertension. [Note added: there are many other examples. The ADD drug Ritalin was originally developed as a remedy for hypotension; Antabus was originally a drug for tropical parasites]
* Kaletra and chloroquine somewhat effective
Convalescent plasma: antibodies from blood of patients who have recovered
*Best advice to young people: wash hands carefully, wear masks, practice social distancing

So what options do countries have that missed the bus for early clampdown South Korean style? This is probably best illustrated by a metaphor from Tomas Pueyo, “The Hammer And The Dance

The basic strategy outlined in that long essay is:
PHASE 1: very tight lockdown for a brief(ish) period to “starve the virus of hosts”: the goal is to get the reproductive number R well below 1, so the infection sputters out over a period of 3-7 weeks. (His guesstimate for R under tight lockdown conditions is 0.35.)
PHASE 2: “the dance”, relax lockdown in combination with intensive tracking and monitoring efforts, targeted quarantine, to keep R from exceeding 1 again

Full interview with Dr. Kim Woo-Ju

COVID19 update, March 27, 2020: (1) how long does the virus survive on surfaces? (2) more anecdata about remdesivir

You have all seen the reports that the virus “survives” for three hours on copper, 1 day on cardboard, 3 days on stainless steel, and whatnot— but what does this really mean?

First of all, “survival” of the virus on a fomite (the epidemiological term for an object that can hold a pathogen and pass it on to another person using the object) is not a binary state. It’s not like if somebody touched your stainless steel doorknob, say, 2d23h ago you will get infected from it, but at 3d exactly you’d be OK. Empirically, “survival” of such pathogens roughly follows an exponential decay curve (like radioactivity), and the meaningfully measurable parameter is the “half-life”, i.e., how much time does it take for the titer (virus “count”) to be halved.

Here is a recent research article in the New England Journal of Medicine where they empirically studied the question for both SARS-CoV-1 (the 2002-3 SARS virus) and the current SARS-CoV-2. http://doi.org/10.1056/NEJMc2004973
It seems that the various “survival” times being bandied about in the popular press correspond to either drops by four orders of magnitude in titer (that’s a bit more than 13 half-lives), or to the point where the pathogen concentration fell below the detection limit.

Excerpt from Figure 1 of the paper, showing uncertainty intervals.

The other item I want to highlight for today: I’ve mentioned the proprietary drug remdesivir (originally developed by Gilead Scientific for ebola) and anecdotal evidence of its effectivity against COVID-19 when used as a “Hail Mary Pass” on a critically ill patient in Washington.
Now (hat tip: Mrs. Arbel) there is more such evidence from Israel (link to Haaretz, which is a far-left newspaper but tends to have fairly reliable science reporting, as so many of its limited readership are in academia):

As for coronavirus patients in serious condition, the ministry proposed – in addition to treating respiratory failure and supportive treatment – using the drug Remdesivir, which was used in the case of Patient 16. The 38-year-old bus driver from East Jerusalem was in serious condition and the drug improved his situation dramatically, so much so that he was in good condition after the treatment.

For background, “Patient 16” who was treated at the Poriah Hospital in Tiberias, had been driving around a group of pilgrims from Greece to Christian sites in Israel, the Palestinian Authority, and Egypt in a tour bus. Upon their return to Greece, 21 of the pilgrims tested positive. It is not clear where they originally got infected.

As I mentioned earlier, “remdesivir is a so-called “nucleotide analog”. In plain English, it pretends to be a nucleic acid (i.e., a letter in the genetic code), but when the “imposter” is being incorporated in a piece of RNA instead of the real nucleotide, it has no place to attach the next one, and copying stops. Thus, the virus cannot reproduce.”

To be updated. Stay healthy, stay safe, and stay calm.

UPDATE 1: Roger Seheult, MD’s medical tutoring channel “MedCram” on YouTube with a video on antibody testing in general, and its specifics in the case of COVID-19

UPDATE 2: The Tagesspiegel (in German) has a very detailed report on “The Taiwanese anomaly”: why the island nation, despite many visitors to and from mainland China, appears to have largely dodged the bullet, without resorting to lockdowns. The article refers to an English-language report in the Journal of the American Medical Association.
TL;DR version: Like in South Korea, an early clampdown, aggressive testing and tracking, and “big data” analytics were the key. Taiwan acted almost immediately following the initial (as we now know, scandalously delayed) December 31 report. While South Korea got its “dress rehearsal” during the limited 2015 MERS outbreak, Taiwan got it during the 2003 SARS outbreak.

COVID19 update, March 26, 2020: antibody testing could be a game changer

Multiple reports are coming in about new tests for SARS-nCoV-2 antibodies being developed and rushed into production:

• USA: Reuters dispatch

• From Belgium, De Standaard (in Dutch) reports on a homegrown antibody test that gives results in 15 minutes

• The UK is days away from rolling out “millions” of a similar test, developed at Oxford University, reports the Sydney Morning Herald.

Why is this a big deal? For one, antibody tests are way faster and easier to administer than the slow PCR testing for the virus itself. This is something that can be scaled up to entire populations of a region.

For another, if this confirms the theory of an Oxford epidemiologist that a substantial percentage of the UK population is already immune to the virus… That would completely transform the economic calculus. People who are immune could simply get tested, get a clean bill of health, and go back to work. This would go a long way to mitigating the economic damage (which ultimately filters down to everybody) of a prolonged lockdown.

Developing…

UPDATE: The New Scientist (UK popular science magazine) reports that Neil Ferguson, the Imperial College modeler whose worst-case scenario predicted two million dead in the US and half a million dead in the UK alone has now drastically revised his predictions, as evidence accumulated that the virus was both spreading more rapidly (with R0 ≈ 3). and had a lower IFR (infection fatality rate) than was originally assumed.

He said that expected increases in National Health Service capacity and ongoing restrictions to people’s movements make him “reasonably confident” the health service can cope when the predicted peak of the epidemic arrives in two or three weeks. UK deaths from the disease are now unlikely to exceed 20,000, he said, and could be much lower.

The need for intensive care beds will get very close to capacity in some areas, but won’t be breached at a national level, said Ferguson. The projections are based on computer simulations of the virus spreading, which take into account the properties of the virus, the reduced transmission between people asked to stay at home and the capacity of hospitals, particularly intensive care units.

[…]

He is also quoted in the same article that “community testing and contact tracing wasn’t included as a possible strategy in the original modelling because not enough tests were available,” but that the UK should have the testing capacity “within a few weeks” to copy what South Korea has done and aggressively test and trace the general population.


(h/t Erik Wingren). Related article.

UPDATE 2: Dr. Deborah Birx, WH Coronavirus Response Coordinator, weighs in on the drastic downward revision

COVID19 update, March 25, 2020: yet another drug target

  1. According to a recent report by Johns Hopkins University, the USA was the best (or least badly) prepared country for a pandemic .

2. Worrying evidence emerges from the CDC that survival of the virus on surfaces in unventilated rooms could be much longer than hitherto assumed—as long as 17 days (!) on the Diamond Princess.

3. Chemical and Engineering News discusses another drug target: the so-called “novel coronavirus main protease dimer” or Mpro:

This enzyme processes a polyprotein chain coded by the virus’s RNA, chopping up the chain into functional proteins that the virus then uses to assemble itself and multiply. Disrupting this key piece of the virus’s self-replication machinery could bring an infection screeching to a halt.

A group led by Rolf Hilgenfeld at the University of Lübeck now has elucidated the structure of this Mpro using synchrotron X-ray radiation, then computationally optimized an inhibitor for it: the alpha-ketoamide compound could even be inhaled rather than injected or swallowed.
(Science 2020, DOI 10.1126/science.abb3405).

This is an angle I hadn’t yet given thought to — and it could be a very selective drug, which should minimize side effects. Staying tuned for this one.

Also at C&EN, this article about repurposing existing arthritis drugs to mitigate “cytokine storm” in severely ill COVID-19 patients.

Be well, be healthy, be safe, be calm!

COVID19 update March 24, 2020: (1) anosmia as an early warning sign? (2) Italy vs. Germany redux.

Dr. John Campbell, a British retired nursing school instructor, has been posting daily COVID19 blogs on YouTube. This is his latest installment:



He draws attention to a paper by the Ear, Nose and Throat [Specialists Association] of the UK,
https://www.entuk.org/sites/default/files/files/Loss%20of%20sense%20of%20smell%20as%20marker%20of%20COVID.pdf
Loss of sense of smell (and taste) is an early symptom of a number of respiratory diseases, and appears to be an early warning sign for COVID19. (Actually, my daughter mentioned this the other day as popping up in a number of first-person stories by people who’d survived COVID19.)

The remainder of his daily update is here:



In an op-ed in the JPost, an investor and chairman of the board of a medical devices company claims he recognizes a “bell-curve” pattern of about 8 weeks in infection statistics of countries.

The extreme difference between CFRs (case fatality rates) in Italy and in Germany (as low as 0.3%) continues to attract attention. This article in Towards Data Science appears to be the original of the article I saw elsewhere. Much of the story is in these two graphs. While the age distribution of the population is actually fairly similar:

The age distribution of patients is actually radically different: predominantly elder people in Italy, predominantly young and middle-age adults in Germany. As I already mentioned in past installments, intergenerational living arrangements are quite common in Italy, comparatively rare in Germany. Homes for the elderly in Germany appear to have gone on lockdown comparatively early.

Also, Germany has been testing more thoroughly than Italy: on average, 3.9 people were tested in Italy per positive result, compared to 13.1 in Germany. A more thorough testing regime likely will pick up more mild cases that in Italy might simply not even appear on the radar.

UPDATE: via Roger Seheult, MD’s video series (COVID19 update 43) on his medicine tutoring channel, I found out about indications (link to SCIENCE) that the obsolete, century-old BCG (bacille Calmette-Guérin) tuberculosis vaccine might impart full or partial immunity against a number of other diseases — including COVID19?

And one Italian village eradicated the infection completely through a program of aggressive testing,

UPDATE 2: (H/t: Jim B.) This could be huge if true: A study by epidemiologist Sunetra Gupta at Oxford (highlighted in the Financial Times) claims that, based on a new epidemiological model, as much as half of the UK population may already be carrying SARS-nCoV-2, with the vast majority of cases asymptomatic or masquerading as mild colds, and that the IFR (infection fatality) would be in the 0.1% range. This would also imply that the UK population would be approaching “herd immunity”, and that hence new case counts should start dropping soon. Time will tell…

Stay-at-home reading promotion: all my ebooks free on Kindle, Wednesday March 25 through Sunday March 29

On account of the various lockdowns around the world, I’m following the lead of several friends who are running free or deep-discount ebook promotions. You can read these books directly on your Kindle, your smartphone (with the free Kindle app for iOS or Android), or you laptop or desktop computer (with the free Kindle app for MacOS or Windows).

WW II alternate history

On March 21, 1943, a general staff officer came within a hairbreadth of killing nearly the entire Nazi top in a suicide bombing.
In timeline DE1943RG, he succeeded.
And then the conspirators discovered killing the tyrant was the easy part of the job.

Episode 3, “Spring Awakening”, is presently in copy-edit.

Campus romance, with lots of music

“On Different Strings: A Musical Romance” was my writing debut. Between a penniless young music tutor and a British-born engineering professor, an unlikely romance cemented by music develops. Until Kafkaesque academic politics and jealous exes make appearances…

Novella

“Winter Into Spring” is a sweet romance novella set in suburban Chicagoland.

Contributions to anthologies

This one I cannot set free, but my story in it fits entirely in the free preview segment, and is hence permafree.

COVID19 update: March 23, 2020. What's in a name?

A reader asked me whether the scientific name is coronavirus, COVID-19, or something else. Without getting into the dispute over the common names, let me address that question specifically.

In a nutshell, coronaviruses are one major family of viruses. What they all have in common is their structure: They consist of a single strand of RNA which encodes the genetic “payload” , a shell of envelope proteins self-assembling around the strand, and a bunch of spikes on the shell whose job it is to stimulate receptors in the cell wall and effect an opening for entry. The spikes look like a kind-of ‘crown of thorns’ under an electron microscope, hence the name ‘coronavirus’.

The most common subgroup humans get exposed to are one type of common cold viruses (although most common colds are caused by rhinoviruses, a different family). There are other coronaviruses that are endemic in poultry and cause upper respiratory tract infections there. Others are endemic in bats, etc.

Alas, some coronaviruses are quite deadly to humans: SARS-nCoV (severe acute respiratory syndrome, novel coronavirus), also known as SARS-CoV, is the one that causes the disease simply named SARS. Originating in horseshoe bats, it somehow crossed the species border and caused a nasty epidemic in mainland China and Hong Kong, with another outbreak hitting Toronto hospitals. CFR (case fatality rate) of the disease is very high, at 9.6%, but no overt cases have reportedly been seen since 2004.

Another is MERS-CoV, causes MERS (Middle East Respiratory Syndrome, one colloquial name being “camel flu”). It apparently crossed the species barrier from bats to camels and thence (possibly via camel-based food products) to humans. MERS has a very high CFR (case fatality rate) of about 1/3 of diagnosed cases, but has a very low reproductive number (in part because it is so deadly?): since it was first described in 2013, we’ve had only about 2000 cases ever worldwide. An outbreak in South Korea in 2015 when a businessman returned from the Arab peninsula appears to have been when the South Koreans got their ‘dress rehearsal’ for how to deal with the present emergency.

The present virus is known as SARS-nCoV-2 because its RNA sequence is so similar (82 % sequence identity) to SARS-nCoV. The mutations that make up the difference (single-strand RNA viruses mutate very rapidly — for reason I’ll explain elsewhere) appear to have had two primary effects: (1) the virus is less deadly; (2) the spikes are more efficient at stimulating ACE2 receptors (angiotensin-converting enzyme 2), which it exploits to enter cells. (Remember, a virus that cannot enter a cell and take over its replication machinery can’t do much of anything. Like a computer virus without a computer ;))

What happens once the virus is inside, by the way? The RNA goes to a ribosome, which are the cell organelles that acts as  protein ‘assembly plant’ of our cells. Gene expression in our cells involves chunks of DNA getting copied onto “messenger RNA”, which then makes its way to the ribosome and gets translated into a protein (by assembling amino acids according to what the “tape” says, until it hits what biologists call a “stop codon”: an “end of message” marker, so to speak). When the viral RNA enters the ribosome instead, that merrily carries out the work order written on the “imposter”, such as the enzyme needed to clone the viral RNA (RdRA, or RNA-dependent RNA polymerase), the envelope proteins, and the spike proteins. There is considerable speculation that the spike proteins in SARS-nCoV-2 are more effective than those in SARS-nCoV.

COVID-19 (coronavirus disease, [first outbreak in] 2019) is what WHO settled on as the name for the disease, not the agent.

UPDATE: statistician and software developer Charlie Martin weighs in more on the Italy data.
And a Japanese financial website reports that the campaign to get the residents of Wuhan to “thank” their dictator backfired badly.
Also, some signs that maybe the anomalously good statistics from Japan may be the product of selection bias: see here (especially the comments) and here. One of the articles, however, made a collateral point I’ve brought up here before:

Cases of seasonal flu have been declining for seven straight weeks, just as the coronavirus was spreading, indicating Japanese may have taken to heart the need to adopt some basic steps to stem infectious diseases. Tokyo Metropolitan Infectious Disease Surveillance Center data shows that influenza cases this year are well below normal levels, with nationwide cases hitting a low according to data going back to 2004.


Also, after Sen. Rand Paul (R-KY), German Chancellor Angela Merkel is the latest politician to go into 14-day quarantine after the doctor or nurse who gave her a standard flu vaccine tested positive for COVID-19.

UPDATE 2: leaked documents appear to indicate that the claim that “there are no new cases in Wuhan” needs to be taken with LOTS of sodium chloride.

UPDATE 3: on the other hand, there is some good news hidden in all the bad (via Instapundit):
And this one gets the Möbius Dick Award: NYT claims travel restrictions didn’t work in China — for the period they weren’t implemented

COVID19: March 22, 2020 update

Finance professor and statistician Peter DaDalt, on his personal FB page, weighs in on the anomalously high CFR (case fatality rate) of 8% from Italy. In contrast, Germany at this stage has an enviable 0.3% CFR.

As I pointed out before, limiting testing to people with already pretty severe symptoms will intrinsically increased the CFR by throttling the denominator. In addition, it is heartbreakingly obvious that the healthcare system in the stricken regions is buckling under the strain.

But there is more than that: Peter cites a professor affiliated with the Italian National Institute of Health, who says that, while yes, all these people are sadly dead, re-analysis of the case files showed that in only about 11% of them COVID-19 was the proximate or underlying cause of death.

Now how is Italy doing during bog-standard seasonal flu? This article (hat tip: LawDog) https://www.sciencedirect.com/science/article/pii/S1201971219303285
states: “We estimated excess deaths of 7,027, 20,259, 15,801 and 24,981 attributable to influenza epidemics in the 2013/14, 2014/15, 2015/16 and 2016/17, respectively, using the Goldstein index.”

That adds up to 68,068 for the four flu seasons together. For comparison, at: https://www.cdc.gov/flu/about/burden/index.html I find US figures for the same seasons of 38,000, 51,000, 23,000, 38,000, i.e. a total of 150,000 for the same four seasons.

Now the populations of the two countries stands at about 60,4M (Italy, 2018 census) and 330M (2019 census estimate. Taking the respective ratios, that works out to 0.045% excess mortality rate for the USA, and nearly two and a half times that, 0.11%, for Italy. Possible explanatory factors include an aged population profile and severe air pollution in some regions (notably Lombardy), but anecdotal evidence from people who have been in the Italian healthcare system suggests there’s more to it than that,

Finally, the US President has authorized Ford, General Motors, and Tesla to engage in mass production of respiration ventilators, as American hospitals are in some areas (notably WA, where the first outbreak took place) reaching the saturation point.

Stay healthy, stay calm, and stay safe.

COVID19: March 21, 2020 update

(1) Israel saw its first death from the epidemic, an 88-year old Shoah survivor from Jerusalem named Aryeh Even. May his memory be for a blessing.

The total number of patients reached 883. Despite “soft lockdown”, people still went out to the beach and to national parks.

(2) Neuroscientist and sci-fi author Robert E. Hampson: reports on an Icelandic biotech company has been organizing a free testing program running in parallel with the official one, and where everybody can ask to be tested. Presumably the purpose is to gather better data about what the small island nation is really dealing with. (At about 335,000, they can in principle test their entire population.)

The biggest takeaway of the results: about one-half of those who tested positive never got ill at all — a number congruent with what is seen on the Diamond Princess.

(2b) From the same post, a preprint on MedRXiv (DOI 10.1101/2020.03.05.20031773 ) of a detailed epidemiological analysis of the Diamond Princess data and of the China data. The central result: they estimate an IFR (infection fatality rate, i.e., dead per number of people infected) of 0.5% (one-half percent), with a 95% confidence interval running from 0.2 to 1.2%, and a CFR (case fatality rate, i.e., dead per number of people who actually get sick) of 1.1%, with a 95% confidence interval running from 0.3 to 2.4%. I certainly hope it’s closer to the bottom than to the top of these CIs.

Israeli epidemiologist Dan Yamin, interviewed here in Haaretz (archive link) argues for low figures as well, and (very much to the distaste of Haaretz’s small, leftist readership) gives Trump’s response positive marks and the WHO’s negative marks. He also stresses what I’ve been suspecting: that anomalously high apparent CFRs in some countries (notably Italy) reflect a selection bias in testing, with scarce testing resources being applied primarily to cases with an already probable COVID19 diagnosis. (Link via Jordan Schachtel.)

We need more and faster testing, and we need it yesterday.



Happy first day of spring, stay healthy, stay safe, stay calm.

Addendum: somebody forwarded a graph highlighting the flatter case incidence graphs for countries like Taiwan, South Korea, Japan, as well as for Hong Kong. Correlation is not causation, of course, and particularly the Japanese by default practice a considerable degree of social distancing on the micro level, but in all of these places, wearing face masks when one has even the slightest hint of a respiratory infection is common social custom. Wearing a mask prophylactically when one is not feeling ill: somebody who lived in Japan for a long time told me people won’t routinely do it except in flu season, but it is definitely socially acceptable.

Addendum 2: The Johns Hopkins COVID19STATS dataset is online here.

Addendum 3: HonestReporting produced this brief memorial video for Aryeh Even z”l.

COVID19 update: a brief look at three possible drugs; Bonus: a brief look at pre-existing conditions in Italy

Yesterday, the Israeli Ministry of Health fast-tracked approval for no fewer than eight experimental therapies for use.

Normally, Phase I, II, and III clinical trials on a drug take a lot of time and effort. But if you are merely repurposing an existing drug for another disease, you can short-circuit a lot of that since you already know safe dosage range and side effects.

These are the three that jumped out at me.

(1) Remdesivir was originally developed by Gilead Science as an anti-ebola drug. It worked against that virus in vitro (i.e. in the lab “test tube”) but not in vivo (i.e. in actual patients). It also worked in vitro against MERS and against the original SARS, so trying it against COVID-19 was worth at least a try.

Which is what was tried as a desperation roll of the dice on an early patient patient in Washington state, with apparently impressive success . Since then, increasing confirmation has been seeping in. Controlled clinical trials are in progress, with results expected next month.

Remdesivir is a so-called “nucleotide analog”. In plain English, it pretends to be a nucleic acid (i.e., a letter in the genetic code), but when the “imposter” is being incorporated in a piece of RNA instead of the real nucleotide, it has no place to attach the next one, and copying stops. Thus, the virus cannot reproduce.

(2) Favipiravir (sold in Japan under the brand name AVIGAN by Toyama Chemicals, a subsidiary of FUJIfilm). This was developed as a broad-spectrum anti-RNA-viral drug. It is an RdRA (RNA-dependent RNA polymerase) inhibitor, i.e., it interferes with the enzyme responsible for copying the viral RNA.

Japanese doctors apparently are using the drug, and China is running clinical trials.

(3) Chloroquine (a 70-year old generic antimalarial), and its close relative hydroxychloroquine, are at first sight the odd duck among the three. It’s obvious why the two above drugs could work, and it appears that they do. But why do we hear a lot about chloroquine these days? Last time I checked, malaria was not even a viral disease?

There is a fairly lucid explanation here of what is going on:

Zn2+ and RdRA discussion about midway through the video

Like for AVIGAN, it’s again about RdRA. Turns out Zn2+ ions latch onto the enzyme and act as an inhibitor. [UPDATE: reference here.] The trouble is getting zinc into the cell. Now in a completely unrelated research project on metallophores as anticancer drugs, it was found that chloroquine is a very good zinc ionophore: https://doi.org/10.1371/journal.pone.0109180

I doubt it is the most effective of the three. On the other hand, chloroquine and its less toxic close relative hydroxychloroquine have been used extensively for decades in areas where malaria is endemic, both for treatment and prophylaxis, so their safety profile and side effects are very well understood. Besides they are very cheap as well. (Report of stocks running out in Western countries: well, these aren’t drugs you routinely stockpile unless you are dealing with malaria all the time… although they have been in some use for lupus and rheumatoid arthritis.) So it apparently has been part of treatment regimes in both Korea (hydroxchloroquine) and China, and it appears to at least some extent in Italy.

Speaking of Italy: yesterday the independent media circulated a report that only 1% of case fatalities in Italy were people without pre-existing conditions. Meanwhile, Bloomberg has picked up the story, and from there I located the original official report (in Italian) on the website of the Italian public health office. This graph is from the Bloomberg report:

and this table (screenshot) comes from the original report

Table 1 from the Italian March 17 report:pre-existing conditions in patients deceased from coronavirus

The Italian names mean, in order, coronary disease, atrial fibrillation, stroke, hypertension, diabetes, dementia, COPD (chronic obstructive pulmonary disease), active cancer in the past 5 years, chronic liver disease, and chronic kidney insufficiency. Needless to say, the statistical risk for ALL of these increases with age, so as patients get older, the percentage of them without any comorbidities will get smaller and smaller.

Stay well, stay safe, and above all, stay calm and rational.

UPDATE: Teva Pharmaceuticals donates 6 million doses of hydroxychloroquine.
And a commenter on Facebook drew my attention to this French clinical trial that just got published (open access PDF here). Especially in combination with azithromycin (presumably for secondary infection prophylaxis), results look very promising.

COVID-19: interesting data from Korea and from the Diamond Princess

One of the first countries to deal with the epidemic was South Korea. Unlike China, South Korea is a fairly transparent society and data published by the Korean CDC (Center for Disease Control) can be more or less taken at face value.

A progress report is published every day on their website: here is today’s edition.

The most interesting part of the report is Table 5, which I am reproducing as a screenshot below:

Table 5 from the Korean CDC report, March 18, 2020

Let’s have a good look at this. Preliminary remark: Korea started a massive testing (according to Table 1 in the same report, nearly 300,000 people have been tested, at a current rate of 10,000 a day) and tracking program early, leveraging all available tech data — privacy concerns be darned.

Observation 1: overall mortality is 1 (one) percent. Still one percent too much, to be sure. But considerably lower than what has been reported from some other places — I suspect because of undertesting.

Observation 2: mortality in the 0-29 age bracket is nil — not one death out of 2,867 patients.

Observation 3: in the 30-49 age bracket, just two (2) deaths out of 2,044 patients, or about 0.1%. Only above 50 does mortality start rising, over 60 in a worrisome fashion. (Not coincidentally, so do comorbidities/pre-existing conditions. I would love to see the statistics broken down between otherwise healthy people and those with chronic cardiovascular/pulmonary/immunity/diabetes problems, or cancer patients. Hypertension is apparently another major risk factor.)

Observation 4: Note the interesting “gender gap”. Men (1.39%) have nearly twice the mortality of women (0.75%). I asked friends on Facebook familiar with South Korea, and they told me over half of men smoke, compared to fewer than five percent of women.

Now what can we expect for older people who are otherwise healthy? Chinese data (caveat lector) suggest overall mortality for patients without comorbidities may be about one-third the overall statistic. https://www.worldometers.info/coronavirus/coronavirus-age-sex-demographics/

And then there is the uncertainty factor of how many people are asymptomatic virus carriers. This is impossible to ascertain without a much more massive testing program (and this isn’t a test you can quickly do with a strip!), but I have seen estimates from 5-7 carriers for each overt disease case.

But the Diamond Princess cruise ship offers an interesting insight. It had nearly 4,000 people on board—many of them in risk groups. (Somebody who used to perform aboard cruise ships quipped that passengers are mostly “the newlywed and the nearly dead” ;)) You’d expect these packed together on a ship in quarantine to be all infecting each others. And yet… 4,061 passengers and crew were examined, on board what effectively became an unintentional virus incubator. Only 712 contracted the virus (about 17.5%), of which 334 asymptomatic (8.2% of the total), leaving 378 (9.3% of the total) ill. Only 7 people died (1.85% of those ill, or 0.17% of all passengers and crew examined), all of them age 70 or older. (Remember, the passenger population is skewed toward the elderly.)

One might treat Diamond Princess stats as an upper limit (since spreading in even dense urban areas will never be as efficient as on a cruise ship) and South Korea as what can be achieved with agile and efficient tracking and containment measures.

Meanwhile, a frantic search for both vaccines and drugs continues. One track that may yield results earliest is the repurposing of existing drugs following off-label testing, since safety and “therapeutic interval” testing have already been done for their original approval. I have mentioned a promising remdesivir trial and I see increasing reports that chloroquine (which has been used for decades as an antimalarial) may interferewith the virus lifecycle. (See e.g., https://www.ncbi.nlm.nih.gov/pubmed/32171740)

Be well, stay healthy, be prepared, and remember:

[L]et me assert my firm belief that the only thing we have to fear is fear itself — nameless, unreasoning, unjustified terror which paralyzes needed efforts to convert retreat into advance.

FDR, inaugural address (1933)

UPDATE: via Behind The Black,

(1) an article in SCIENCE about South Korea and how it got a “wake-up call” in 2015 when a businessman brought back MERS from the Middle East

(2) a lengthy analysis of the Diamond Princess data
(3) are there 6 asymptomatic or “too mild to notice” cases for each clinical case?

(4) https://www.statnews.com/2020/03/16/lower-coronavirus-death-rate-estimates/

UPDATE 2: computational biochemistry pioneer Michael Levitt (2013 Nobel Prize in Chemistry shared with Arieh Warshel and Martin Karplus) sounds an optimistic note based on what he knows. His comments start off with Israel (he divides his time between Weizmann and Stanford) but then go on to the rest of the world.

Containment measures may create an offsetting factor for COVID-19 mortality

Something occurred to me as I saw a sign in our elevator telling us to refrain from leaning on the sides, and to wash our hands upon entering the house:

The excess mortality from the current COVID-19 epidemic may be offset to a smaller or larger extent by the mitigating effect “social distancing” behavior will have on seasonal flu.

Keep in mind that every winter, according to CDC data, complications from seasonal flu account for as many as 61,000 excess deaths (winter of 2018-9) in the USA. Many of the people dying are the same as are most at risk from COVID-2019: the elderly, the immunocompromised, people with chronic illnesses. A very nontrivial percentage of these deaths are preventable not just through vaccination, but also through sensible social distancing and hygiene measures. The latter applies even more outside the USA, for example in much of Europe or in the Middle East where the concept of “personal space” is nearly foreign.

Yes, you say, but few people die directly from seasonal flus, and most deaths are actually from opportunistic superinfections (usually pneumonia). True, but: (1) the end result for patients is, sadly, the same; (2) more and more bacterial pneumonia is caused by multiply antibiotic-resistant strains against which the usual pharmaceutical arsenal is increasingly powerless. (I’ve lost a couple too many colleagues and friends to resistant infections that would have responded quickly to antibiotics 30 years ago.); (3) many of these people would never have gotten the same pneumonia if their immune systems weren’t already dealing with the flu.

A friend who is a geriatric nurse told me that many of the social distancing and hygiene measures now recommended for COVID-2019 are just more stringent reiterations of what she’s been telling people to do for years.

Even if they were to make only a 10-20% dent in excess mortality from seasonal flu epidemics, that would be a reduction of 6,000-12,000 in the USA alone that would offset the increased excess mortality from this novel respiratory infection. It may sound like a meager silver lining on a dark and uncertain cloud, but it is definitely some positive food for thought.

Meanwhile, stay well, stay safe, and let us hope we will all weather this storm as well as can be. It is good to remember the whole quote from FDR’s inaugural address:

So, first of all, let me assert my firm belief that the only thing we have to fear is fear itself — nameless, unreasoning, unjustified terror which paralyzes needed efforts to convert retreat into advance.

UPDATE: Some “anecdata”: Friends who live in the North of Japan counts a number of local healthcare professionals among their friends. Normally, a hefty percentage of case load at the local hospital consists of elderly with complications from flu or viral pneumonia. Reportedly, things are much slower in that regard since COVID-19 got people minding their social distance again…

Purim 5703/1943 in another timeline: Excerpt from Operation Flash, Episode 1

Happy Purim to my fellow Jews! May the day be filled with joy despite the worldwide anxiety about the COVID-2019 epidemic.

It hasn’t always been a joyous occasion: during the Shoah, henchmen of the modern Haman “marked” the holiday in their own cynical way. As we learn from Wikipedia:

Nazi attacks against Jews were often coordinated with Jewish festivals. On Purim 1942, ten Jews were hanged in Zduńska Wola to “avenge” the hanging of Haman’s ten sons.[92] In a similar incident in 1943, the Nazis shot ten Jews from the Piotrkówghetto.[93] On Purim eve that same year, over 100 Jewish doctors and their families were shot by the Nazis in Częstochowa. The following day, Jewish doctors were taken from Radom and shot nearby in Szydłowiec.[93] In an apparent connection made by Hitler between his Nazi regime and the role of Haman, Hitler stated in a speech made on January 30, 1944, that if the Nazis were defeated, the Jews could celebrate “a second Purim”.[93] Indeed, Julius Streicher was heard to sarcastically remark “Purimfest 1946” as he ascended the scaffold after Nuremberg.[94]

[In fact, said occasion was on a different Jewish holiday, namely Hoshana Rabba

I am about to start pre-publication editing of Episode 3 of my World War Two alternate history series, “Operation Flash”. The premise of this series, of course, is that the March 21, 1943 suicide bombing attempt on Hitler and his main underlings had succeeded. (Colonel Rudolf Freiherr von Gersdorff would only have needed to use a different detonator.)
As I was writing Episode 1, I suddenly thought: “Hmm, let me check what day March 21, 1943 was on the Jewish calendar”. Sure enough, 14 Adar 5703 would have been the mother of all Purims in that timeline. So I could not resist splicing in a chapter about this, which also gave me a chance to touch on some other issues. Below I am reproducing this chapter.

Happy Purim!


***

Operation Flash — Episode 1 — Chapter 6

Berlin-Wedding
Germany
March 21, 1943

For the whole world, my name was Johann Schulze. I must never mention my old name, Joachim Israel Steinberg.

My father had been a well-known doctor. When the law forbidding Jewish doctors to treat non-Jewish patients came out, we tried to make ends meet. I somehow got a job at the Siemens-Halske electrical factory.

For one reason or another, some of my coworkers took a liking to me. So when the transports to the East started, we were distributed across a few families. Fortunately, I don’t look very Jewish, so I can “submarine”, as we call it. There are a number of us fellow “U-boats” hiding in plain sight in the city — right in the heart of the Third Reich. We are always on the lookout for Gestapo agents — and for traitors of our own, who for money or a temporary reprieve for their families ferret out fellow Jews for the Gestapo.

If anyone asked, I was originally from Lübeck, but our house had been destroyed in the major RAF raid, and my maternal uncle, Christoph Baumann, had taken me in. Some people would shake their heads in sympathy — “to flee bombardments to Berlin is like fleeing the rain into the gutter”. I would say I was “hoping to join the Wehrmacht soon”, or perhaps “wanted to join the Luftwaffe to help defend the Reich against the terror bombers”, but meanwhile was working at a factory essential for the war.

My sisters had an easier time submarining elsewhere, and actually worked in various jobs. Unlike me, they did not carry the sign of the Covenant, of course—if arrested and made to strip, I’d be done for.

***

We’d had a simple meal, mostly bread and a watery soup made of potatoes. This was one reason each family had only taken in one of us: unless we could somehow get registered under a false name and get ration cards issued, each hidden person was an additional mouth to feed with the same number of ration cards.

Occasionally I would take the risk and work an odd job as a day laborer, and with the money Mrs. Baumann could buy some food on the black market. She would also quietly sell family curios and jewelry, one item at a time, if needed. It wasn’t impossible to survive that way, as Mr. Baumann and his eldest son Peter had increased rations as “essential war workers”. Peter had lost a foot stepping on a mine during the France campaign and had been invalided out of the army.

The large radio, built at the same factory they worked, was one luxury we did have.

***

“I don’t get it. Are they drunk on the job?”

“Why?” I walked in from the other room, where I’d been reading.

“In the middle of the news overview, the radio suddenly went to a Franz Léhar tune.

“And then, after about a minute, it went back to the newsreader.”

Suddenly we heard him pause, clear his throat, and speak, with a jittery voice.

***

“We interrupt this program for a special announcement.”

“Proclamation Number One of the Reichsnotregierung!”

We looked at each other. Emergency Reich Government?!

The Führer—”, he paused, “The Führer, Adolf Hitler, is dead!

What?! We were dumbstruck. The newsreader continued.

“He was killed in a bomb attack together with the Deputy Führer, Reich Marshal Hermann Goering; with the Head of the Wehrmacht High Command, Field Marshal Keitel; with the Führer’s Chief Adjutant, Gen. Rudolf Schmundt; and many others.

“A conscience-less clique of party and SS leaders who are strangers to the front have attempted to stab the struggling soldiers in the back and to grab power for self-serving purposes.

“Therefore we, the Emergency Reich Government, have assumed executive power. In order to maintain law and order, the ERG has declared a state of martial law and delegated responsibility to the Supreme Command of the Wehrmacht.

“1. The following are subordinated to the ERG and the Army:”

We listened in disbelief as a long list of Nazi Party institutions were declared either subordinate to the government or outlawed.

“…Effective immediately, the Waffen SS is to be integrated into the Wehrmacht. Any resistance to this order will be regarded as mutiny and punished as such.

“3. The Allgemeine SS and its associated organizations are declared illegal…”

None of us could believe our ears. Would this long nightmare at last be over?!

“…Any resistance to the military authorities is to be ruthlessly suppressed. The Fatherland is in its hour of greatest peril.

“The German soldier is faced with an historic task. It will depend on his energy and behavior whether or not Germany will be saved.

“Signed:

Ludwig Beck, Reichsverweser.

Dr. Carl Goerdeler, Chancellor.

Field Marshal Erwin von Witzleben, Commander in Chief of the Wehrmacht.”

* * *

Shock and elation filled the room; it was difficult to know if it all could be contained. The Baumanns had been Social Democrats during the Weimar Era. Mr. Baumann had been a member of the Reichsbanner Black-Red-Gold and later, when that merged with two other groups, of the Iron Front — which had fought both the SA brownshirts and the Communist “Red Front”. Somehow, he had escaped persecution after the Nazi takeover.

Meanwhile, “Siegfried’s Death” by Wagner had started playing from the radio.

“Now this senseless war will end,” Mrs. Baumann murmured, “and the troops will come home.”

“That won’t be easy,” Mr. Baumann replied. “The remaining Nazis won’t give up without a fight.”

“Perhaps Johann can come out of hiding,” daughter Ruth spoke up. For some reason, Ruth is a very popular girl’s name among Germans—even those who begrudge us the whites in our eyes, as we say here. This does not include our Ruth, mind you.

“Again, make haste slowly. And don’t go cheering too hard outside. You never know.”

I could speak only one word.

Purimfest. Purimfest.

“Come again?” Peter asked.

“Today would have been the holiday of Purim.”

“Yes?”

“It’s where we read the book of Esther, about how an evil man named Haman tried to kill all the Jews in Persia and they were saved.”

“I remember this book from Bible School,” Mrs. Baumann added. “Esther and her uncle Mordechai stopped him.”

“And Haman was hanged from the gallows he had prepared for Mordechai.”

I had lost my faith some years ago. But this was surely a most remarkable coincidence.

25 Luglio 1943: Dino Grandi and the fall of Mussolini

This is the original radio announcement on the Italian radio from July 25, 1943 at 10:45pm:

[My translation:] “Attention! Attention! His Majesty the King and Emperor, [Victor Emmanuel III,] has accepted the resignation of the Head of Government, Prime Minister, and Secretary of State, Mr. Benito Mussolini, and has appointed to [these same offices] His Excellency, Marshal of Italy Pietro Badoglio.”

The bloodless coup that had occurred the day before was in no small measure the brainchild of a now forgotten Italian politician: Dino Grandi, 1st Count Mordena.

Bundesarchiv, Bild 102-00160 / CC-BY-SA 3.0

Dino Grandi had been one of “Il Duce”s earliest companions. Originally he had left-wing sympathies like Mussolini himself (many people forget that “Il Duce”s first major political engagement was as the editor-in-chief of the Italian socialist newspaper Avanti! [Forward!]). Like in “Il Duce”, World War One awakened nationalist tendencies in Grandi. He was one of the 35 Fascist delegates elected to the Chamber of Deputies in 1921. From September 1929 until July 1932, he served as Foreign Minister, in which position he apparently possessed some skill: particularly with the United Kingdom, the anglophile Grandi built up good relations.

Considering Grandi’s attitude to the League of Nations too accommodating, Mussolini dismissed him and took up the portfolio himself, before later passing it on to his son-in-law Galeazzo Ciano (whose diaries are a valuable primary source). 

Grandi was appointed ambassador in London as a kind of consolation prize. He reportedly had affairs with a number of high-society ladies, notably Lady Alexandra Curzon, the daughter of Viceroy of India, Lord Curzon. (Said daughter simultaneously was carrying on with both British Union of Fascists leader Oswald Mosley and with the Foreign Secretary, Viscount Halifax).

At the outbreak of the war, Grandi was recalled when Hitler found out about Grandi’s attempts to negotiate a separate nonaggression pact between Italy and the UK, and went ballistic on Mussolini. The latter appointed Grandi Minister of Justice upon his return. Later he became Chair of the lower house of the quasi-parliament, the Chamber of Fasci and Corporations [“corporations” in the sense of estates, professional associations, and the like — in keeping with Mussolini’s “corporatist” ideology].

Grandi opposed both antisemitic legislation (introduced in 1938 under Nazi pressure) and Italy’s entry into the war, and his increasing criticism of Mussolini’s policy led to his ouster from the cabinet on February 5, 1943. Crucially for what follows, however, he remained a member of the Grand Council of Fascism.

By this time, the continued military bad news from the Eastern Front and North Africa had reduced Mussolini to a state of near-catatonia, and increasingly, senior Fascists started grumbling that Il Duce had become unfit for the job. 

Now much unlike the Führer — who was accountable to no-one (except arguably Satan) — Mussolini still had a measure of accountability to the Grand Council of Fascism, as well as to the head of state, King Vittorio Emanuele III. The latter, under Article 5 of the Statute Albertino (the constitution of Sardinia and later of Italy until 1948),  had the constitutional prerogative to appoint and dismiss all government officials, including the Prime Minister: he was, however, reluctant on principle to exercise this power.

Then, on July 10, 1943, the Allies invaded Sicily, which was the last straw for Grandi, Ciano, and many others. Grandi, as the bearer of the country’s highest decoration, had free access to the king and sounded him out. An agreement was reached that, if the Grand Council of Fascism were to recommend Mussolini’s dismissal, then the king would carry it out.

Grandi scheduled a meeting of the Grand Council of Fascism on Saturday evening, July 24, 1943 at its usual location in the aptly named “Sala del Pappagallo” (Parrot Room, after the parrot Pope Paul II had kept there  https://www.romasegreta.it/campitelli/piazza-venezia.html [in Italian]) of the Palazzo Venezia on San Marco Square. The ostensible reason was the presentation to Mussolini of a new book.  

There, within sight of the Forum as well as of Trajan’s Market, the Duce was suddenly presented with a motion to invoke Article 5 (implied: for the King to dismiss Mussolini).

Following a lengthy debate and a break, the 28 members voted by roll call on Grandi’s motion: 19 voted in favor, 7 against, 1 abstained, and one left the room. At 2:40am on July 25, the council broke up for what turned out to be the last time.

Mussolini requested an audience with the king, who agreed to receive him at 5pm. There and then, he was told he was dismissed from his offices and that Marshal of Italy Pietro Badoglio had been appointed in his place. 

Upon emerging from the palace, a specially briefed detachment of Carabinieri accompanied the Duce “for his own protection” to a military ambulance that turned out to be a disguised “Black Maria” taking him to prison.

And thus ended the reign of Il Duce. Two months later, an SS commando team led by Otto Skorzeny would spring him from imprisonment. Brought to Hitler, he was told he would now be the head of a  puppet state in the German-occupied zone of Italy (what became known as the “Italian Social Republic”). Mussolini was at that point ill, exhausted, and looking forward to retirement, but the German tyrant threatened to have several Northern cities flattened by the Luftwaffe unless he consented. So he spent the remaining fewer than two years of his life a nominal dictator, but a prisoner in fact.

As for Dino Grandi, he fled abroad to Portugal and then Brazil — where he became a successful businessman — but eventually would return to Italy and die there at a ripe old age.

Operation Eclipse: How Churchill and Canadian troops saved Denmark from Stalin in the last days of World War Two

Mark Felton just posted a video about a fascinating episode in the last days of WW II

Mark Felton video about Operation Eclipse

View the whole thing. But here is a quick summary:

At Yalta, the Elbe River had been the agreed-upon demarcation line between the Red Army and the Western allies. On April 25, 1945, the Red Army and the US Army had met at Torgau on the Elbe, effectively cutting what remained of the “Thousand-Year” Reich into two.

Winston Churchill, however, feared that if the Russians were allowed to reach the Elbe river in the North, they would be able to march into Schleswig-Holstein and thence into Denmark — adding that to their growing inventory of Soviet satellite states.

So a group of Canadian paratroopers was sent on a deep-penetration raid across the Elbe to capture and hold the Baltic port of Wismar, and block the Soviet advance there. The Canadians encountered negligible resistance — instead, they ran into thousands of Wehrmacht soldiers eager to surrender to the Western Allies. In order not to be slowed down in their advance, the Canadians disarmed the soldiers and sent them on an unaccompanied march toward the Elbe, while they continued.

Eventually they made their objective. Shortly after they had occupied the town (against no resistance other than sporadic sniper fire), advance scouts for a Red Army tank column showed up — they were headed for the Hanseatic city of Lübeck — confirming Churchills’s suspicions, as Lübeck was the Eastern gateway to Schleswig-Holstein and then Denmark.

An uneasy standoff ensued, but no open hostilities. Of course the Canadians had to be withdrawn just days later — but their maneuver had bought Montgomery and Churchill enough time to accept the surrender of the remaining German forces in Northern Germany and in Denmark.

This was not the most glamorous or heroic operation of WW II — but it achieved an important objective, and materially affected the power relationships between NATO and the USSR in years to come. And, of course, it spared the Danes from life as a Soviet satellite.

Two cheers for Winston, and for Canadian paratroopers! And thanks to Mark Felton for sharing this unknown but important tale with us.

UPDATE: more on Operation Eclipse here: https://www.historylearningsite.co.uk/world-war-two/world-war-two-and-eastern-europe/operation-eclipse/