COVID19 update, June 14, 2020: avoiding the Three C’s of Transmission; most asymptomatic cases remain asymptomatic

Busy workday, so just some quick updates:

(1) (hat tip: Masgramondou): Are Technica: “Just 10-20% of cases are behind 80% of transmission” 

Benjamin Cowling, a Hong Kong-based epidemiologist and biostatistics expert, agrees. Cowling and colleagues recently studied transmission in Hong Kong, finding superspreading events drove local transmission. In a recent op-ed, he and a colleague argue that public health policies aimed at stopping the pandemic should focus on stopping superspreading.

“The epidemic’s growth can be controlled with tactics far less disruptive, socially and economically, than the extended lockdowns or other extreme forms of social distancing that much of the world has experienced over the past few months,” the researchers wrote

In an email to Ars, Cowling fleshed out this idea a bit, noting that “measures that specifically target superspreading are those that reduce or prevent large gatherings of people,” such as those to reduce the density of people in schools and workplaces.

Measures not specifically targeted to superspreading, he noted, “are those like asking everybody to stay at home as much as they can, despite many workplaces and social settings not being places that superspreading could occur.”

In the op-ed, Cowling noted that Japan—which has been relatively successful at managing the pandemic—has employed an anti-superspreading policy called [“the Three Cs Of Transmission”]: Avoid (1) Closed spaces with poor ventilation, (2) Crowded places, and (3) Close-contact settings, such as close-range conversations. The risk for superspreading is highest in situations with all three Cs.

[…]Cowling and his colleagues’ analysis has been posted online but has not yet been peer-reviewed or published in a scientific journal. But, they note, their findings from Hong Kong aren’t unique. For instance, a study published in the Lancet in April, which looked at transmission of SARS-CoV-2 in Shenzhen, China, found that just around 9 percent of cases accounted for 80 percent of transmission. And a modeling study from researchers in London likewise found that just about 10 percent of cases may account for 80 percent of transmission.

Read the whole thing.

(2) via Instapundit, this report by UPI quoting this letter to the New England Journal of Medicine from a Japanese team:

http://doi.org/10.1056/NEJMc2013020

The outbreak of coronavirus disease 2019 (Covid-19) on the cruise ship Diamond Princess led to 712 persons being infected with SARS-CoV-2 among the 3711 passengers and crew members, and 410 (58%) of these infected persons were asymptomatic at the time of testing[….] A total of 96 persons infected with SARS-CoV-2 who were asymptomatic at the time of testing, along with their 32 cabinmates who tested negative on the ship, were transferred from the Diamond Princess to a hospital in central Japan between February 19 and February 26 for continued observation. Clinical signs and symptoms of Covid-19 subsequently developed in 11 of these 96 persons, a median of 4 days (interquartile range, 3 to 5; range, 3 to 7) after the first positive polymerase-chain-reaction (PCR) test, which meant that they had been presymptomatic rather than asymptomatic.

[…] The group of persons with asymptomatic SARS-CoV-2 infection consisted of 58 passengers and 32 crew members, with median age of 59.5 years (interquartile range, 36 to 68; range, 9 to 77). A total of 24 of these persons (27%) had coexisting medical conditions, including hypertension (in 20%) and diabetes (9%). The first PCR test at the hospital was performed a mean of 6 days after the initial positive PCR test on the ship. The median number of days between the first positive PCR test (either on the ship or at the hospital) and the first of the two serial negative PCR tests was 9 days (interquartile range, 6 to 11; range, 3 to 21), and the cumulative percentages of persons with resolution of infection 8 and 15 days after the first positive PCR test were 48% and 90%, respectively. The risk of delayed resolution of infection increased with increasing age.

In this cohort, the majority of asymptomatically infected persons remained asymptomatic throughout the course of the infection. The time to the resolution of infection increased with increasing age.

 

(3) UnHerd: so where did the virus really come from? Dogmatic answers do not behoove a scientist, as the writer rightly argues. On the other hand, extraordinary claims (e.g., a genetically engineered virus) require extraordinary proof. Either way, we need all the evidence we can get. Read the whole article.

This is in the realm of speculation, but I’ve been wondering: what if, after the outbreak began, local officials panicked thinking this may be a human-“improved” virus that had escaped from the WiV, then calmed down once it became clear it was “only” another novel coronavirus. That would explain some of the skittish behavior in the very beginning, the destruction of samples,…  

ADDENDUM: yes, public health experts are undermining themselves by U-turning on recommendations for political expedience. 

And Insta snarks “nothing to see here, move along”: Parts of Beijing locked down due to fresh virus cluster

ADDENDUM 2: Israeli public health expert on what we might face in the winter 

COVID19 update, June 13, 2020: Belgium takes a breather; the Jewish community of Antwerp; High-fructose corn syrup

 

(1) Belgium for a stretch has had the highest per capita COVID19 mortality in the world (except for the microstate of San Marino — beware of statistics of small numbers), with almost 10,000 dead out of a population of about 11 million. But now it seems to have turned the corner at last—daily dead are in the 10 range, down from 2-300 at the peak of the epidemic. 

BelgiumCOVIDdead

So the chair of the Corona Committee, virologist Steven De Gucht, gave his last of 54 press conferences for now, looking back at the past three months. “As quickly as the dark clouds gather, just as quickly can the sun break through again,’ Van Gucht said somewhat emotionally. This is the last press conference. We can let go of the reins a little. We’ve grabbed the virus by the neck and extinguished fires. It is clear that nature can be very harsh.” Future updates will be via weekly press releases, at least until (if ever) there is a second wave.

Current COVID19 measures are detailed on a dedicated website in four languages, including in (fairly idiomatic) English. At this point, all stores are open (night stores until 1am), as are (with capacity restrictions) restaurants with table service and bars. Sports teams, musical ensembles, and theater group may practice but not yet perform for an audience: starting July 1, audiences of up to 200 are permitted (which works for the local equivalent of off-Broadway theater and for junior league soccer teams). 

(2) Also in Belgium, in an area about six square blocks by the Antwerp railway station, is the Diamond District, home to about 20,000 mostly Orthodox or Chareidi (“ultra-Orthodox”) Jews. This community has given Antwerp the nickname ‘Jerusalem on the Scheldt’ in some circles. The Jerusalem Post looks at how this community has weathered the COVID19 storm: fairly well, all told. “The community projected in March that 85% of its members could contract the coronavirus because of its close conditions and frequent social interactions, and that over 500 could die. A communal taboo about dealing with the virus, which some labeled as a scourge of the secular world, added to the danger.” In the event, only 11 (eleven) community members succumbed to the virus, all elderly and/or with major pre-existing conditions. 

 

The community […] at first downplayed the danger of the virus […] but […]  took swift action following the death rate projection, implementing strict social distancing measures that included the closure of all synagogues on March 13 — five days before federal authorities imposed a nationwide lockdown. 
 
“It’s just a few days, but with a pandemic that grows exponentially it was a crucial early step,” said [Shlomo] Stroh, who was involved in the decision-making process led by the city’s chief rabbi, Aaron Schiff, and the city’s beit din, or rabbinical court. 

Getting the Orthodox Jewish community of Antwerp to adhere to social distancing was a “gradual process,” according to Claude Marinower, an alderman in charge of the city government’s communications efforts, among other portfolios. 
 
“At first there was some pushback” from some community members against the closure of synagogues, said Marinower, who is Jewish but is not Orthodox. But “there was more cooperation as the dimensions of the pandemic emerged — and especially in Belgium, where about 10,000 people have died of the coronavirus.” 
 
“When rabbis issued strong instructions against gatherings, it was accepted by all,” Marinower said.
 
Michael Freilich, an Orthodox Jewish lawmaker from Antwerp who serves in the federal parliament, also attributed the low death rate among Jews to a combination of rabbinical leadership and authorities’ strict enforcement. Together, he told JTA, “it meant we were saved from disaster.”

With the fairly narrow streets inside the district, a creative solution to communal prayer was found: a cantor would lead the service from the street and worshipers would join in from the balconies. Some non-Jewish neighbors lodged police complaints about the noise, but others welcomed the relief from the silence during the lockdown as well as “the chance to hear what goes on inside the synagogues”. (I would imagine that anybody who has serious issues with Jews would not voluntarily live in an area of Antwerp that is best described as an urban shtetl.)

 

(3) Roger Seheult MD has videoblogged extensively on the benefits of vitamin D and zinc for the immune system generally and during the COVID-19 epidemic in particular, as well as the value of the antioxidant and mucolytic NAC (N-acetylcysteine) as a food supplement.  This time, however, he talks about something to avoid for a change: fructose and specifically high-fructose corn syrup.

http://doi.org/10.3390/nu9040405

 

Diabetes prevalence was 20% higher in countries with higher availability of HFCS compared to countries with low availability, and these differences were retained or strengthened after adjusting for country-level estimates of body mass index (BMI), population and gross domestic product (adjusted diabetes prevalence=8.0 vs. 6.7%, p=0.03; fasting plasma glucose=5.34 vs. 5.22 mmol/L, p=0.03) despite similarities in obesity and total sugar and calorie availability. These results suggest that countries with higher availability of HFCS have a higher prevalence of type 2 diabetes independent of obesity.

https://doi.org/10.1080/17441692.2012.736257

And yes, much of it is about type 2 diabetes (a major risk factor with COVID-19) but there’s more to the story. Go watch the whole video.

 

 

Friday night delight: Liszt,. Concert Etude #3 in Db major, “Un Sospiro” (a sigh)

[no COVID19 post today — probably tomorrow]

Here are two performances of a little gem among Liszt’s earlier, flashier work. Before Liszt retired from the concert stage, his archival was the now-mostly forgotten Sigismund Thalberg, whose “party trick” was to keep a melody going on top of a two-handed accompaniment. Liszt was dismissive of what he might have called a “gimmick” of he spoke English, but he then exploited it to great effect in some of his own compositions, notably the famous “Liebestraum” in Ab major, and the following piece. Enjoy!

 

 

And while I’m at it, let me share a piece in the same key that appears in Operation Flash, Episode 3, where the two protagonists meet, and Diana Slater lacks the words to tell Felix Winter what is on her mind. 

COVID19 update, June 11, 2020: vitamin D as “the low-hanging fruit of the epidemic”; deficiency statistics for Israel; first monoclonal antibody for COVID19 enters clinical trials

(1) John Campbell and Roger Seheult both again have videos on vitamin D

Apparently, the French medical academy now also got in on the act. Adapted from his notes: There is a significant correlation (95.4% confidence) between vitamin D deficiency and mortality from COVID-19. This phenomenon follows a North-South gradient, but Nordic countries are the exception, as foods there are routinely fortified with vitamin D (since the long subarctic winter otherwise causes major problems).  Spain and Northern Italy have counterintuitively high rates with vitamin D deficiency, as they do not normally fortify foods nor take supplements.

 

 

Now I got curious about Israel with its sunny climate, and found this in the IMAJ (Israel Medical Association Journal)

(journal issue from the publisher) (ResearchGate entry for paper)

 

As you can see in Table 3 (screenshotted below), there is a difference between Ashkenazi Jews (i.e., those whose ancestors came from Central and Eastern Europe), non-Ashkenazi Jews (in Israeli public discourse, actual Sephardim — descendants of the Spanish Expulsion — are commonly lumped in with Yemenite, Iraqi, Iranian,… Jews who descend from their own Diaspora branches), and Israeli Arabs. While there are some quite swarthy Ashkenazi Jews (as in: swarthy enough to pass for Arab), and conversely there are non-Ashkenazi Jews and Arabs who are quite light-skinned, the difference between the population averages is quite obvious. And indeed, this is reflected the vitamin D deficiency statistics below. Even with the small sample, statistics are significant at the 95% or more level.

Table 3 upper

Now elderly people of any ethnicity have more vitamin D deficiencies to begin with. So what is the sample is narrowed down to people aged between 20 and 50? That’s the lower pane of that table:

 

Table3 lower

Look, it’s a trade-off. Darker skin means you can spend more time outdoors in sunny climates without getting sunburned (the origin of the term “redneck”) or (G-d forbid) developing skin cancer. But it does make you more at risk  for vitamin D deficiency — and all that entails for the immune system —  if you live at northern(-ish) latitudes and/or spend most of your time indoors.

And you just have to stick the title of this paper in Google Scholar and look at the papers citing it to see a pile of studies linking vitamin D deficiencies with adverse outcomes for all sorts of illnesses. 

Medscape referred to vitamin D as “the low-hanging fruit of the epidemic”. It sure is.

 

(2) Chemical and Engineering News reports  that Eli Lilly has started phase 1 clinical trials with a monoclonal antibody. 

The discovery effort began at the end of February. Now, just 3 months later, Lilly says it has given the experimental antibody, called LY-CoV555, to the first participants in a Phase I clinical study of people hospitalized with COVID-19. The trial began more than a month ahead of the companies’ earlier goal of late July.

The 90-day turnaround from discovery to injection is likely a record for monoclonal antibody drug development. LY-CoV555 may also be the first experimental drug designed after the discovery of SARS-CoV-2 to be tested as a treatment for COVID-19. The dozens of therapies already tested in COVID-19 patients—including remdesivir, an antiviral made by Gilead Sciences—were discovered before the pandemic and are now being repurposed to fight the coronavirus.

LY-CoV555 targets the spike protein of SARS-CoV-2 and in preclinical studies prevented the virus from infecting human cells. Scientists hope that mass-producing these antibodies will help clear the virus from people who are already infected and struggling to recover. Antibodies could also be given to healthy people to help prevent an infection for a few weeks or months. That prophylactic approach could prove useful for high-risk people, including those with compromised immune systems and medical workers who face frequent exposure to the virus. […]

LY-CoV555 targets the spike protein of SARS-CoV-2 and in preclinical studies prevented the virus from infecting human cells. Scientists hope that mass-producing these antibodies will help clear the virus from people who are already infected and struggling to recover. Antibodies could also be given to healthy people to help prevent an infection for a few weeks or months. That prophylactic approach could prove useful for high-risk people, including those with compromised immune systems and medical workers who face frequent exposure to the virus.

Lilly’s program is one of about two dozen underway to develop monoclonal antibodies that target SARS-CoV-2. Several other firms, including Regeneron and Vir Biotechnology, expect to begin clinical trials of their antibodies in June or July.

The main goal of Lilly’s Phase I clinical trial is to see if LY-CoV555 is safe, but the company is taking the unusual step of including a placebo group in the study. That could provide early signs of whether the drug is working. Lilly says that it expects results by the end of June and that it will begin a larger, Phase II trial soon after if the drug appears safe.

Lilly has already begun large-scale manufacturing and is working on having several hundred thousand doses ready by the end of the year.

The discovery effort began Feb. 25, when AbCellera received a plasma sample obtained from a person who had been infected with SARS-CoV-2 and had recovered. That plasma contained precious B cells—the antibody factories of our immune systems. AbCellera scanned through more than 5 million B cells to find ones that made antibodies targeting the SARS-CoV-2 spike protein.

 

(3) Both masgramondou and a friendly writer sent me links to this article in al-Grauniad (https://archive.is/lkKN0) I am glad to see that exasperation at repeated “coat-turning” on lockdown and social distancing measures is not just the province of political conservatives and libertarians. 

 

 

COVID19 update, June 10, 2020: Interview with Norwegian public health chief; tug-of-war over testing in Israel; COVID-19 outbreak on Dutch mink farms

Some quick updates after a long, busy workday.

(1) UnHerd interviews Norway’s public health chief, Camilla Stoltenberg. [Her brother is NATO Sec.Gen., father was FM of Norway]. 

At 7:30 into the video. Camilla Stoltenberg says that it was with hindsight unnecessary to close down schools.

Distance: we had 2m until recently, now we updated to 1m because so few people still have the virys

Face masks: Norway has no general mandate, and she sees no adequate reason for one.

It is interesting that she, and her Swedish colleague Anders Tegnell, started out from very different positions and converge at least partly toward each other.

(2) Israel is seeing a second ripple, if not a second wave. Pretty much nobody has the stomach for a second lockdown, so “test, track, trace” is the mantra. Haaretz reports |(h/t: Mrs. Arbel) on the tug-of-war to control the testing effort. In one corner is  the  emergency commission, led by Weizmann Institute professor Eli Waxman, which stresses efficiency and rapid turnaround. In the other corner is the healthcare bureaucracy which appears to fear encroachment on its territory., and as the remedy for its comparatively slow turnaround proposed budget and personnel increases for itself.

Honestly, I am somewhat puzzled why RT-PCR testing somehow must be under the auspices of healthcare bureaucrats when Israel has a solid biotech industry and research academia that has come up with some very creative ideas in the area of high-throughput testing.

(3) Coronavirus rips through Dutch mink farms, triggering culls to prevent human infections, reports the news section of SCIENCE magazine. (A preprint of the paper is at https://doi.org/10.1101/2020.05.18.101493v1 )

The mink outbreaks are “spillover” from the human pandemic—a zoonosis in reverse that has offered scientists in the Netherlands a unique chance to study how the virus jumps between species and burns through large animal populations.

But they’re also a public health problem. Genetic and epidemiological sleuthing has shown that at least two farm workers have caught the virus from mink—the only patients anywhere known to have become infected by animals. SARS-CoV-2 can infect other animals, including cats, dogs, tigers, hamsters, ferrets, and macaques, but there are no known cases of transmission from these species back into the human population.

The first two mink outbreaks were reported on 23 and 25 April at farms holding 12,000 and 7500 animals, respectively. More mink were dying than usual, and some had nasal discharge or difficulty breathing. In both cases, the virus was introduced by a farm worker who had COVID-19. Today, it has struck 12 of about 130 Dutch mink farms. Once COVID-19 reaches a farm, the virus appears to spread like wildfire, even though the animals are housed in separate cages. Scientists suspect it moves via infectious droplets, on feed or bedding, or in dust containing fecal matter.

That mink are susceptible wasn’t a surprise, because they are closely related to ferrets, says Wim van der Poel of Wageningen University & Research, which has an animal health laboratory here. (Both mink and ferrets can also contract human influenza viruses.) Like humans, infected mink can show no symptoms, or develop severe problems, including pneumonia. Mortality was negligible at one farm and almost 10% at another. “That’s strange—we don’t really understand it,” says virologist Marion Koopmans of Erasmus Medical Center in Rotterdam. Feral cats roaming the farms—and stealing the mink’s food—were found to be infected as well. 

The Netherlands is the only country so far to have reported SARS-CoV-2 in mink. In Denmark, the world’s largest mink producer, “We have not recorded any similar disease or outbreaks,” says Anne Sofie Hammer, a veterinary scientist at the University of Copenhagen. Neither has China, the second largest producer, says virologist Chen Hualan of the Chinese Academy of Agricultural Sciences. (Hubei, the province hardest hit by COVID-19, does not have mink farms, she notes.)

The Dutch outbreaks are giving scientists a chance to study how the virus adapts as it spreads through a large, dense population. In some other animal viruses, such conditions trigger an evolution toward a more virulent form, because the virus isn’t penalized if it kills a host animal quickly as long as it can easily jump to the next one. (Avian influenza, for instance, usually spreads as a mild disease in wild birds but can become highly pathogenic when it lands in a poultry barn.) Although SARS-CoV-2 is undergoing plenty of mutations as it spreads through mink, its virulence shows no signs of increasing.

Read the whole thing. The article also points out that mink farming, under pressure from animal rights’s groups. will be banned in the Netherlands from 2024 on anyhow, so a number of farmers may decide to throw in the towel early.

(4) How predictable. How transparent. How pathetic.

[NB: I haven’t forgotten about yesterday’s NATURE paper on NPI’s, but want to blog about it when I’m not asleep on my feet.]

 

 

 

COVID19 update, June 9, 2020: Matt Ridley on parallels with the 1890 flu epidemic; 57% infected in Bergamo, Italy; corroboration of different susceptibilities between blood groups

(1) (H/t: masgramondou). Matt Ridley tells the story of the 1890 Russian flu epidemic 

The killer came from the east in winter: fever, cough, sore throat, aching muscles, headache and sometimes death. It spread quickly to all parts of the globe, from city to city, using new transport networks. In many cities, the streets were empty and shops and schools deserted. A million died. The Russian influenza pandemic of 1889-90 may hold clues to what happens next — not least because the latest thinking is that it, too, may have been caused by a new coronavirus.

In addition to the new diseases of S[ARS], M[ERS], and C[COVID]-19, there are four other coronaviruses that infect people. They all cause common colds and are responsible for about one in five such sniffles, the rest being rhinoviruses and adenoviruses. As far as we can tell from their genes, two of these coronaviruses came from African bats (one of them bizarrely via alpacas or camels), and two from Asian rodents, one of the[se] via cattle.

It sounds very  familiar… (Note that at the time, not everybody even believed in bacteria — and the first virus was only discovered eight years later by Martinus Beijerinck.)

Genetic analysis by the Belgian virologist, Prof. Marc van Ranst at the University of Leuven, suggests OC43, one of the four common cold coronaviruses diverged away from a pneumonia virus in cattle around 1890. Matt Ridley describes the hypothesis that OC43 was the pathogen of the 1890 Russian Flu, then gradually evolved away to a much more contagious, but infinitely less harmful, form.

 

 

The first case is thought to have been in Bukhara, in central Asia in the spring of 1889, but by October, Constantinople and St Petersburg were affected. In December, military hospitals in the Russian capital were overcrowded, factories and workshops closed for lack of workers and ‘whole districts of the city were abandoned by the population’, according to one report. The symptoms were said to include headache, fever, aching bones, facial rash and swollen hands. The illness lasted for five or six days but sometimes left the patient exhausted for weeks.

The virus reached Paris in November. By the turn of the year, with hospitals full, patients were housed in military barracks and tents in the city’s parks. […] In Vienna the schools closed early for Christmas and stayed closed till late January. In Berlin, it was reported that many post-office staff were affected. In London so many lawyers fell ill that the courts were closed for a while. One day in January at St Bartholomew’s Hospital in the City of London, Dr Samuel West found more than 1,000 people crowded into the casualty ward, most of them men.[Sounds familiar?] […]

According to a modern analysis, the death rate peaked in the week ending 1 December 1889 in St Petersburg, 22 December in Germany, 5 January 1890 in Paris, and 12 January in the US. [The basic reproductive number] R0 has been estimated at 2.1 and the case fatality rate was somewhere between 0.1 per cent and 0.28 per cent: similar figures to today’s pandemic.

Contemporary newspaper reports say that like today’s epidemic, the Russian flu appeared to attack adults more than children, and in some schools the teachers were all affected but not the pupils. Like today’s virus, it was, intriguingly, reported to affect men much more badly than women. Newspapers were filled with statistics of mortality, anecdotes and reassuring editorials.

By March 1890 the pandemic was fading in most places, just as common colds and flu do in spring today. The seasonal pattern displayed by colds and flus is so striking that it cannot be a coincidence that today’s pandemic was also in retreat by May all around the world, irrespective of the policies in place. By the northern summer of 1890 the virus was ensconced in the southern hemisphere, having reached Australia in March. It returned to Europe the following winter and for several years after.

If OC43 was the cause of the 1889-90 pandemic — far from proven, of course — and given that it is the cause of perhaps one in ten colds today, then it has evolved towards lower virulence. It is easy to see how this occurs with respiratory viruses, which are transmitted by people chatting and shaking hands. Mutations that affect the severity of the virus also tend to have an impact on whether people pass it on: if it sends you to bed feeling rotten, you will not give it to so many people. In the inevitable struggle for survival, the milder strains will gradually displace their nastier ones. This is why so many cold viruses affect us but so few kill us, except maybe when new to our species.

Perhaps, too, a degree of immune response in the population helps moderate the effects of the virus, even if not achieving full and permanent immunity. Some cross–immunity seems to exist today, whereby those who have had coronavirus colds do not catch, or do not suffer severely from, Covid-19.

 

(2) Die Welt reports that in the Italian city of Bergamo (classical music lovers may think of Debussy’s Suite Bergamasque) no fewer than 57% of 10,000 tested subjects had antibodies for COVID19. (This is most definitely in 1st-order ‘herd immunity’ territory.) Among a similar-sized (10,400) sample of healthcare workers, “only” 30% had antibodies (which is in the 2nd-order herd immunity range).

In a summary of the state of the epidemic so far, the German daily quotes virologist Prof. Christian Droste, who in an interview in Der Spiegel states that with our present state of knowledge, it is time to shorten the 2-week quarantine in case of exposure to just one week.

(3) A German-Norwegian collaboration, reports Die Welt, found confirmation of earlier indications that blood groups have an effect on disease progression. A+ are worst off (oh joy ;)), while O imparts a degree of protection.

Dass die Blutgruppe Krankheitsverläufe beeinflussen kann, ist grundsätzlich nichts Neues. So gibt es schon seit Längerem Hinweise darauf, dass Blutgruppe 0 auch vor schweren Malaria-Verläufen schützen kann, dafür aber anfälliger für Magen- und Darminfektionen macht, während Träger der Blutgruppen A, B oder AB besser gegen die Pest gewappnet sind.

[That blood groups can influence disease progression is fundamentally nothing new. There have for long been indications that blood group O can also protect for severe malaria [!!], but makes one more susceptible for gastro-intestinal infections, while carriers of blood groups A, B, or AB are more resistant to the plague.

Preprint: https://www.medrxiv.org/content/10.1101/2020.05.31.20114991v1.full.pdf+html

Laut Blutspendedienst des Bayerischen Roten Kreuzes haben 37 Prozent der Bevölkerung die Blutgruppe A Rhesus Positiv und 35 Prozent die Blutgruppe 0 Rhesus Positiv.

[According to the blood donation service of the Bavarian Red Cross, 37% of the [German] population have blood group A+ and 35% O+.]

(4) A new Nature paper “Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe”

http://doi.org/10.1038/s41586-020-2405-7

(This is a “postprint”, i.e., accepted version after peer review, but without copy-editing by the publishers and corrections in proof.) I will probably devote tomorrow’s edition to discussing this paper. (The hoary sketch comes to mind: “Why are you spraying pesticides on an organic garden?” 

“Those aren’t pesticides, that’s a powder against elephants.”

“But there aren’t any bleeding elephants here!”

“Yeah, good stuff, huh?”)

 

(5) Apropos of nothing:

“Liberty is for science what air is for an animal: when deprived of liberty, [science] dies of suffocation as surely as a bird deprived of oxygen. […]

Thought must never submit —

neither to dogma,

nor to party,

nor to passion,

nor to special interest,

nor to a preconceived idea,

nor to anything but the facts themselves —

for when thought submits,

that means it ceases to be.”

—Henri Poincaré, Le libre examen en matière scientifique (1909)

COVID19 update, June 8, 2020: timeline pushed back to October 2019?; leaked German Interior Ministry internal report; hydroxychloroquine prophylactic use study

Just a few quick updates today, as things were busy at work.

(1) The time line for the epidemic keeps getting pushed back further? According to an ABC exclusive report , satellite imagery of parking lots of Wuhan hospitals in October 2019, compared to the same month the previous year, indicate unusual levels of activity. Moreover, internet searches on Baidu at the time supposedly had a number of queries for flu/SARS like symptoms. I am not wholly convinced, but who knows?

 

(2) An internal German report from “Referat KM4” of the BMI (Federal Interior Ministry), that was strongly critical of the “overreaction” of the German government to the pandemic, was leaked to the press. A PDF of the full text is here: (accompanying provenance info): Powerline has a summary in English. A little googling turned up an organigram in which KM4 shows up as “Schutz kritischer Infrastrukturen” (protection of critical infrastructures), one of six Referate (idiomatically: desks, sub-departments) in the department Krisenmanagement und Bevolkungsschutz (Crisis Management and Population Protection).

The report argues that mortality is a small fraction of the annual all-cause mortality in Germany [of course, this argument is open to the “well, that is so because we took action quickly” argument], and indeed, worldwide excess mortality at the time of writing (May 11) was one-sixth of that during the 2017/8 seasonal flu epidemic.

I haven’t waded through the entire report, which is nearly 100 pages long, but it is preceded by a 2-page Kurzfassung (“short version”, idiomatically “Executive Summary”). Item 3 of the Executive Summary speaks of a “Fehlalarm” (false alarm) and laments:  

The fact that the suspected false alarm remained undetected for weeks has a major reason
that the existing framework for action of the crisis unit and the
crisis management in a pandemic do not include appropriate detection tools that
automatically trigger an alarm and initiate the immediate cancellation of measures
as soon as either a pandemic warning turned out to be a false alarm or
it is foreseeable that collateral damage — particularly in terms of destruction of human lives — threatens to become larger than the health consequences and especially the lethal potential of the disease under consideration.

The report explicitly distances itself from economic cost-benefit calculations and, in item 4, argues that collateral damage in lives is larger than the damage of the original epidemic. 

Probably the most inflammatory sentence of the executive summary is “One reproach [from the public] might be that, in the Corona crisis, the State has shown itself to be one of the greatest producers of fake news” (Ein Vorwurf könnte lauten: Der Staat hat sich in der Coronakrise als einer der größten fake-news-Produzenten erwiesen.)”

German governmental authorities have tried to dismiss this report as “one person’s opinion”, but — agree with the report or not — it seems to be a good deal more than that. 

(3) Dr. Seheult looks at another hydroxychloroquine clinical trial: this time it looks at a prophylactic regime.

https://doi.org/10.1056/NEJMoa2016638

A group of about 800 patients who reported high-risk contact (nearer than 6th for more than 10 minutes) with a known COVID-19 carrier was split into two arms. One arm was given a 5-day hydroxychloroquine (HOcq) regimen, the other a placebo. Interestingly, and noted by Dr. Seheult, again no zinc!

The percentage of people who developed COVID19 was somewhat lower in the HOcq arm (11.8%) than in the placebo arm (14.3%), but with this sample size, there is about one chance in three the difference is due to chance. (What he didn’t highlight is that, even with high-risk contacts, the risk of contagion is much lower than you might intuitively expect.) 

A fairly large proportion of test subjects in the HOcq arm reported gastrointestinal complaints, but interestingly, no severe adverse events were reported. (HOcq is known to lead to QT-prolongation: in combination with other drugs that do this, such as the macrolide antibiotic azithromycin, the cumulative effect may lead to heart arrhythmias.)

Anyway, let Dr. Seheult explain it himself:

 

(4) Dr. Mike Hansen discusses differences between autopsy reports of COVID19 deaths and deaths from seasonal flu

COVID19 update, June 7, 2020: Do-it-yourself COVID-19 tests found to be more accurate as well as comfortable; Israeli study confirms protective effect of smoking?!; “half of colleges may close in the next 5-10 years”

(1) Via Instapundit, a popular writeup of a study that found samples acquired by the patients themselves were more accurate than the usual deep nasal and pharyngeal swabs, and not just more comfortable. Besides, they are less likely to expose healthcare personnel, as deep sampling often causes sneezing, coughing, and gagging.

I should perhaps clarify here that the accuracy-limiting factor of RT-PCR testing, at this point, is not the testing apparatus at all (with lab-prepared samples, accuracy approaches 100%) but the sampling technique.

 

The original scientific article about the study was published in the New England Journal of Medicine: http://doi.org/10.1056/NEJMc2016321

Here is an animation of how, once the sample has been acquired, RT-PCR testing works in the lab.

 

(2) There were several reports that, counterintuitively, smokers were underrepresented among COVID19 positive cases. Now in https://www.medrxiv.org/content/10.1101/2020.06.01.20118877v2.full.pdf is an intriguing large-sample study from doctors associated with Clalit Health Services, the largest HMO in Israel which has about 3 million patients in its central database. [Full disclosure: we are insured through a competitor. All four authorized HMOs operate such databases—unlike with Surgiscape, I have every reason to believe these data are kosher.]

As of the cutoff date (May 16), over 145,000 adults insured with Clalit underwent RT-PCR testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2),  3.3% of which tested positive. After discarding cases aged under 18 and over 95, as well as those where it was unknown whether they smoked or not, the authors were left with 4,235 positive tests and 124,192 negative. Out of the latter, they randomly selected a control sample of 20,755 patients (5x as many) that matched statistical make-up of the positive sample in terms of gender, age distribution, and ethnosocial group — Jewish Orthodox, Arab, General(mostly Jewish non-Orthodox).

Guess what: Statistically, 9.8% of the  COVID19 positive cases smoke currently, one-half the percentage in the control group 18.2%. Because of the large sample size, p<0.001, i.e., the probability that this result could have arisen from “the luck of the draw” is less than 0.1%. There was no significant difference for past smokers (11.6 vs. 12.9%) — it’s definitely got something to do with current smokers (nicotine or some other component of tobacco smoke).

Of the COVID19-positive tests, 1.8% deceased, 2.0% hospitalized in severe condition, 4.0% in moderate condition, 15.0% in mild condition, the remaining 77.2% did not require hospitalization. There was no significant correlation between the degree of severity and the patient’s smoking status.

Changeux et al11, relying on similar observations, propose a crucial role for the nicotinic acetylcholine receptor (nAChR) in COVID-19 pathology. According to their neurotropic hypothesis, SARS-CoV-2 invades the central nervous system through the nAChR receptor, present in neurons of the olfactory system, as reflected by the frequent occurrence of neurologic symptoms, such as loss of smell or taste, or intense fatigue in patients affected by COVID-19. Other mechanisms may also affect SARS-CoV-2 infection potential in smokers. It is widely accepted that the angiotensin converting enzyme 2 (ACE2) represents the main receptor molecule for SARS-CoV-2, and smoking has been shown to differentially affect ACE2 expression in tissues12–14. Other putative explanations could involve altered cytokine expression such as IL-6, for which increased levels are associated with unfavorable disease outcome14,15.

 

 

(3) Business school professor admits that as many as half of tier-2 colleges will be gone in the next 5-10 years. This was a bubble waiting to burst anyway: the COVID-19 crisis and the attendant shift to online learning is just precipitating the burst, the way Amazon and online shopping more generally were the downfall of many a brick-and-mortar store.

(4) This is the sort of behavior that makes me cringe in embarrassment for my profession. True scientists follow the facts wherever they lead, and seek the truth wherever it may be found. Political hacks exist in every profession — but they are especially grating in ours. And when the public loses all faith in us because of such politicized hacks, it will be blamed on “anti-science” and anti-intellectualism.

 

COVID 19 update, June 5, 2020: ex-MI6 chief drops bombshell; “chaos disguised as strategy”; Trump admin selects shortlist of five vaccine candidates

(1) The former head of MI6 (the UK’s foreign intelligence service — its CIA if you like), Richard Dearlove, says flat-out COVID-19 was engineered in a Chinese lab but escaped from there. 

He continues:

Although he did not believe that the Chinese released the virus intentionally, Sir Richard told the Telegraph that the Chinese regime handled the outbreak very differently from the way a Western government might have dealt with it, and that the incident should be a wake-up call for the rest of the world on underestimating the scope of Chinese global ambitions. 
“Look at the stories… of the attempts by the leadership to lockdown any debate about the origins of the pandemic and the way that people have been arrested or silenced,” he said. “I mean, we shouldn’t really have any doubt any longer about what we’re dealing with. 
“Of course, the Chinese must have felt, well, if they’ve got to suffer a pandemic maybe we shouldn’t try too hard to stop, as it were, our competitors suffering the same disadvantages we’ve got. 
“Look, the Chinese understand us extremely well. They have made a study of us over the last decade or longer, particularly through attending our universities. We understand the Chinese very poorly. It’s an imbalanced relationship in that respect.” 
Australia has been taking the lead on pushing for an “impartial, independent and comprehensive evaluation” of the global response to COVID-19, an ambition which was agreed to by the World Health Organization in late May. China launched cyberattacks and trade restrictions against the Antipodean state in response. 
“I think it’s very courageous of the Australians to take China on,” Sir Richard said. “I mean, there’s an obvious, huge imbalance in terms of power, both economic and military and political, but they are showing the way. You have to have a critical relationship with China.” 
He urged the British authorities to do the same, calling for the government to scrap plans to place the construction of Britain’s new 5G network in the hands of Chinese telecoms firm Huawei, and to reduce reliance on Chinese-made personal protective equipment for health workers. 
“We need to go into reverse,” he said. “It’s important that we do not put any of our critical infrastructure in the hands of Chinese interests. So telecommunications, Huawei, nuclear power stations, and then things that, you know, we require and need in a crisis, like PPE.” 
“We have allowed China so much rope that we are now suffering the consequences, and it’s time to pull the rope in and to tighten the way we do business. It’s very, very important that we keep a keen eye on this and do not allow the Chinese to, as it were, benefit strategically from this situation that has been imposed on all of us.”

Wow.  

(2) Die Welt (in German) continues to pour withering criticism on the Swedish sonderweg. They call it “chaos disguised as strategy” (Chaos getarnt als Strategie). Private corporations are now stepping up with immunity testing for pay. Due to high demand, they had to limit their offerings to Sweden’s two largest cities, Stockholm (by far hardest hit) and Göteborg, but other companies are looking to fill the void. 

Sweden’s chief epidemiologist, Prof. Anders Tegnell, gave a remarkably self-critical interview on Swedish radio: “Too many have died too soon”. He regrets not having been more proactive to protect the most vulnerable. My translation (2nd hand via German): “I believe there is definite room for improvement in what we ‘ve been doing in Sweden, of course., And it would have been good if we’d known more precisely what to close to prevent infection spread.” Also, he said, if we’d encountered the same epidemic but with the knowledge we have today, then the correct course in his opinion lay intermediate between the road Sweden took and what the rest of the world did. “Unambiguously, we could have done better in Sweden, I believe.”

(3) Operation Warp Speed, an initiative of the White House, selected a shortlist of five vaccine candidates for mass manufacturing in the US

The five vaccines include Moderna’s mRNA1273, currently in phase 2 trials; AstraZeneca and Oxford University’s AZD1222, now in clinical trials at multiple UK sites; a candidate from Johnson & Johnson; a Merck vaccine based on that company’s successful Ebola vaccine; and Pfizer and BioNTech‘s BNT162.

The accelerated programs are funded through $10 billion from Congress and $3 billion directed for National Institutes of Health (NIH) research.

Earlier this week, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said he was confident more than one COVID-19 vaccine would prove effective in a reasonable period of time.

Francis Collins, MD, NIH director, said some vaccine candidates will be ready for large-scale testing as soon as the beginning of July. The phase 3 trials would involve as many as 30,000 volunteers for each candidate vaccine, with half the volunteers receiving a placebo, Collins told National Public Radio.

If successful, this will be the most rapid vaccine development program in history.

 

ADDENDUM: GenomeWeb reports that another Surgiscape-sourced paper, in the New England Journal of Medicine, has now been retracted. 

The Lancet and the New England Journal of Medicine have retracted two COVID-19 papers because of questions regarding the data used in the studies. The papers were both previously the subject of expressions of concern.

The now-retracted Lancet paper had reported that the antimalarial drugs hydroxychloroquine and chloroquine may increase the risk of death among COVID-19 patients, while the now-retracted NEJM paper noted that though cardiovascular disease increases someone’s risk of dying from COVID-19, ACE inhibitors did not increase that risk.

Both studies relied on a database run by Surgisphere, which said it had detailed data on about 100,000 COVID-19 patients from 1,200 hospitals around the world, but as the New York Times noted earlier this week, clinicians and medical researchers have raised concerns about the data it houses.

The authors of the Lancet study who were not associated with Surgisphere noted in the expression of concern that they would be seeking an independent audit of the data. However, in the retraction notice, they wrote that Surgisphere would not transfer the full dataset to its independent reviewers, citing client agreements and confidentiality. Because of this, the Lancet notes in a statement that three of the four authors — the fourth author being Surgisphere chief executive Sapan Desai — said they “can no longer vouch for the veracity of the primary data sources.” 

The NEJM retraction notice similarly says that the authors, this time including Desai, could not “validate the primary data sources” and requested a retraction.

COVID19 update, June 4, 2020: is the virus a picky eater; co-authors of influential Lancet hydroxychloroquine study retract paper

(1) Somebody quipped to me the other week: “the virus is a picky eater”. Now, Prof. Karl Friston of UC London, a well-known neuroscientist and computational modeler who is a member of “the independent SAGE committee” is interviewed here on UnHerd.

Now, from the unlikely source of a prominent member of the “Independent SAGE committee”, the group set up by Sir David King to challenge government scientific advice and accused by some of being populated with Left-wing activists, comes a claim that the true portion of people who are not even susceptible to Covid-19 may be as high as 80%.

 

A written essay is here. His thesis: 

Theories abound as to which factors best explain the huge disparities between countries in the portion of the population that seems resistant or immune — everything from levels of vitamin D to ethnic-genetic and social and geographical differences may come into play — but Professor Friston makes clear that it does not primarily seem to be a function of government coronavirus policy. “Solving that — understanding that source of variation in terms of this non-susceptibility — is going to be the key to understanding the enormous variation between countries,” he said.

Controversial? We link, you decide.

(2) The Washington Examiner reports that the influential The Lancet paper, which claimed hydroxychloroquine was more harmful than helpful in the treatment of COVID19 based on dodgy Surgisphere data, has now been retracted by 3 of the 4 authors (the 4th is the CEO of Surgisphere). Here is the original retraction notice:

https://www.thelancet.com/lancet/article/s0140673620313246

After publication of our Lancet Article,1 several concerns
were raised with respect to the veracity of the data
and analyses conducted by Surgisphere Corporation
and its founder and our co-author, Sapan Desai, in
our publication. We launched an independent third-
party peer review of Surgisphere with the consent of
Sapan Desai to evaluate the origination of the database
elements, to confirm the completeness of the database,
and to replicate the analyses presented in the paper.

Our independent peer reviewers informed us that
Surgisphere would not transfer the full dataset, client
contracts, and the full ISO audit report to their servers
for analysis as such transfer would violate client
agreements and confidentiality requirements. As such,
our reviewers were not able to conduct an independent
and private peer review and therefore notified us of their
withdrawal from the peer-review process.

We always aspire to perform our research in accordance
with the highest ethical and professional guidelines. We
can never forget the responsibility we have as researchers
to scrupulously ensure that we rely on data sources that
adhere to our high standards. Based on this development,
we can no longer vouch for the veracity of the primary
data sources. Due to this unfortunate development, the
authors request that the paper be retracted.

We all entered this collaboration to contribute
in good faith and at a time of great need during
the COVID-19 pandemic. We deeply apologise to
you, the editors, and the journal readership for any
embarrassment or inconvenience that this may have
caused.

The accompanying statement by the Lancet editorial board:

Statement from The Lancet
Today, three of the authors of the paper, “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis”, have retracted their study. They were unable to complete an independent audit of the data underpinning their analysis. As a result, they have concluded that they “can no longer vouch for the veracity of the primary data sources.” The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics (COPE) and International Committee of Medical Journal Editors (ICMJE), institutional reviews of Surgisphere’s research collaborations are urgently needed.

(3) Elsewhere in the Lancet is an article with a “meta-analysis” of other studies (in plain English: a study in which the raw data of several original lstudies are combined into a larger dataset and the statistical analysis repeated in order to achieve greater productive power than the individual studies)  on the effectiveness of distancing, face masks, and eye protection, in both  healthcare and non-healthcare (community) settings.

https://doi.org/10.1016/S0140-6736(20)31142-9

From the summary (paragraphing and emphasis mine):

Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients).

Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio [aOR] 0·18, 95% CI 0·09 to 0·38; risk difference [RD] –10·2%, 95% CI –11·5 to –7·5; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2·02 per m; p_interaction=0·041; moderate certainty).

Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0·15, 95% CI 0·07 to 0·34, RD –14·3%, –15·9 to –10·7; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12–16-layer cotton masks; p =0·090; posterior probability >95%, low certainty).

Eye protection also was associated interaction with less infection (n=3713; aOR 0·22, 95% CI 0·12 to 0·39, RD –10·6%, 95% CI –12·5 to –7·7; low certainty).

Unadjusted studies and subgroup and sensitivity analyses showed similar findings.

 

ADDENDUM: “WHO frustrated by China’s info delays as coronavirus started to spread, report finds”. Is this damage control/reputation management on the part of the WHO, or the genuine expression of frustration by the technical levels of the organization? More about this tomorrow, G-d willing.

COVID19 update June 3, 2020: serological study in Israel; Surgisphere data scandal [UPDATED]

(1)  Israel is planning to test a sample of 70,000 people for antibodies. Earlier, preliminary result from a smallish sample of 1,709 Israelis found that 2.5±0.5% had antibodies for the virus. With official infection numbers (positive tests in RT-PCR) reaching only 0.2% of the population, this implies a Dunkelziffer  (stealth infection rate) of 10-15 times the official one — not dissimilar from what Prof. Hendrik Streeck found in Germany or the team of Ioannides, Bendavid et al. found in Santa Clara County, CA. [For non-American readers: Santa Clara County is almost synonymous with Silicon Valley.] 

With just 291 dead out of 17,377 confirmed cases — a raw case fatality rate (CFR) of 1.67%, this implies that the infection fatality rate is just 0.11–0.17%. This is considerably lower than even the drastically downward-revised CDC figures,  (IFR of about 0.26%), but Israel has a much younger population pyramid than the USA, and is sunny enough that vitamin D deficiency should not be as prevalent as in  northern US states.

Meanwhile, Israel is seeing a flare-up of cases in schools that has some people speaking of a second wave, although it might actually be more like a ripple, or a round of the dance in Tomas Pueyo’s “Hammer and Dance” strategy. Rungholt blogs in German about her experience as a kindergarten teacher in a kibbutz in the far North of the country.

(2) h/t: Cathe Smith: several papers, including the one that led to suspension of the hydroxychloroquine trials, now under a cloud owing to suspect medical database

On its face, it was a major finding: Antimalarial drugs touted by the White House as possible COVID-19 treatments looked to be not just ineffective, but downright deadly. A study published on 22 May in The Lancet used hospital records procured by a little-known data analytics company called Surgisphere to conclude that coronavirus patients taking chloroquine or hydroxychloroquine were more likely to show an irregular heart rhythm—a known side effect thought to be rare—and were more likely to die in the hospital.

Within days, some large randomized trials of the drugs—the type that might prove or disprove the retrospective study’s analysis—screeched to a halt. Solidarity, the World Health Organization’s (WHO’s) megatrial of potential COVID-19 treatments, paused recruitment into its hydroxychloroquine arm, for example. (Update: At a briefing on 3 June WHO announced it would resume that arm of the study.)

But just as quickly, the Lancet results have begun to unravel—and Surgisphere, which provided patient data for two other high-profile COVID-19 papers, has come under withering online scrutiny from researchers and amateur sleuths. They have pointed out many red flags in the Lancet paper, including the astonishing number of patients involved and details about their demographics and prescribed dosing that seem implausible. “It began to stretch and stretch and stretch credulity,” says Nicholas White, a malaria researcher at Mahidol University in Bangkok.

Today, The Lancet issued an Expression of Concern (EOC) saying “important scientific questions have been raised about data” in the paper and noting that “an independent audit of the provenance and validity of the data has been commissioned by the authors not affiliated with Surgisphere and is ongoing, with results expected very shortly.”

Hours earlier, The New England Journal of Medicine (NEJM) issued its own EOC about a second study using Surgisphere data, published on 1 May. The paper reported that taking certain blood pressure drugs including angiotensin-converting enzyme (ACE) inhibitors didn’t appear to increase the risk of death among COVID-19 patients, as some researchers had suggested. (Several studies analyzing other groups of COVID-19 patients support the NEJM results.) “Recently, substantive concerns have been raised about the quality of the information in that database,” an NEJM statement noted. “We have asked the authors to provide evidence that the data are reliable.”

A third COVID-19 study using Surgisphere data has also drawn fire. In a preprint first posted in early April, Surgisphere founder and CEO Sapan Desai and co-authors conclude that ivermectin, an antiparasitic drug, dramatically reduced mortality in COVID-19 patients. In Latin America, where ivermectin is widely available, that study has led government officials to authorize the drug—although with precautions—creating a surge in demand in several countries.

Chicago-based Surgisphere has not publicly released the data underlying the studies, but today Desai told Science through a spokesperson that he was “arranging a nondisclosure agreement that will provide the authors of the NEJM paper with the data access requested by NEJM.”

UPDATE (h/t LIssa Hailey): much more at The Guardian (archive copy here) “Governments and WHO changed Covid-19 policy based on suspect data from tiny US company”

A search of publicly available material suggests several of Surgisphere’s employees have little or no data or scientific background. An employee listed as a science editor appears to be a science fiction author and fantasy artist. Another employee listed as a marketing executive is an adult model and events hostess.

[…] Until Monday, the “get in touch” link on Surgisphere’s homepage redirected to a WordPress template for a cryptocurrency website, raising questions about how hospitals could easily contact the company to join its database.

[…] At a press conference on Wednesday, the WHO announced it would now resume its global trial of hydroxychloroquine, after its data safety monitoring committee found there was no increased risk of death for Covid patients taking it.

The article refers to an earlier expose at MedicineUncensored.

COVID19 update, June 2, 2020: Remdesivir Phase 3 trial results

A short post today, as the day job is keeping me busy. 

 

(1) Today the results of the Phase 3 remdesivir trial were released. (I previously discussed its mechanism of action here: in brief, it’s a nucleoside analog that interferes with viral RNA copying by acting as an “imposter letter” in the RNA genetic code and causing further copying to break off.)

Again, as with prior trials, we see that it’s not a “magic bullet” drug, but clearly has a therapeutic advantage  in patients with moderate disease (signs of pneumonia, but don’t yet need oxygen). The trial used almost 600 patients, divided into three roughly equal groups: (a) standard of care (SOC) + 5-day remdesivir; (b) SOC + 10-day remdesivir; (c) SOC only (control group). In the table below, percentages are given in parentheses:UntitledImage

The “ordinal scale” is an ad hoc 7-point scale ranging from hospital discharge on one end to death on the other end. In the 5-day regimen (which I read between the lines uses twice the dose for half the time), about 10% more patients see an improvement, and 8% fewer patients see a worsening from baseline than with SOC. No patients on the 5-day regime died (compared to four with SOC), but we are in “statistics of small numbers” territory.

As for drug side effects (“AE”), there are about 6% more than with standard care, but actually fewer serious side effects.

Additional Phase 3 trials in severe and moderate disease are in progress in various countries. The drug is currently approved in Japan and under FDA emergency authorization in the US.

 

(2) A few videos:

A 60 Minutes Australia documentary on the Chinese cover-up (see also my earlier post about Fang Fang’s “Wuhan Diary”)

In this video, Dr. Seheult talks about masks and about a database for vaccine clinical trials.

 

 

ADDENDUM: Israeli-developed “disinfection tunnel” sprays harmless disinfectant aerosol generated electrolytically from water and salt

COVID19 update, June 1, 2020: Sweden’s “road alone” and elderly care; avoiding lockdowns in a new flare-up; not even Stanford immune from cuts and layoffs

 

(1) Sweden’s Sonderweg (“special road”, idiomatically, “going its own way”) is the subject of heated debate pro and con.

At first sight, per capita mortality is an order of magnitude higher than in adjacent countries with similar ethnic profile, climate, and sociology. (Sweden does, however, have a higher percentage of 1st-generation immigrants than Norway, Denmark, and Finland — see below.)

At second sight, however, it turned out that Swedish morbidity and especially mortality is disproportionately concentrated in two populations: elderly in care homes (over 70%) and 1st-generation immigrants. Mortality among native Swedes from young to independent elderly, is actually not that elevated compared to the neighbors. 

On the gripping hand, while the Swedes may have avoided the economic ruination of a full lockdown and may be closer to herd immunity now should a second wave arrive, there are costs to this epidemic for everyone (the travel and airline industries, for instance, are on life support everywhere, lockdown or no lockdown). Some aspects of the world economy will be changed forever — and some already existing ‘creative destruction’ trends will be accelerated worldwide. Sweden will see a recession, just not as deep, and possibly with a quicker recovery. 

But let’s come back to those care homes. Die Welt has an exposé on what is going on there: “The true problem of the Swedish sonderweg“. If it were in English, I’d say “read and weep”. But as it’s in German, let me summarize a few points (reader beware):

  • As explained earlier, the Swedish elderly care model is based on encouraging people to live independently for as long as possible, with paid ‘home helpers’ if needed. Assisted living facilities seem to be primarily a private-sector option, while true homes for the elderly are seen as the last resort. Median survival time in them is less than a year
  • Caregivers in these homes were alleged not issued PPEs, and testing was only carried out people who showed symptoms, despite adequate testing capacity being available.
  • The Swedish newspaper Aftonblådet quoted gerontologist Prof. Yngve Gustafsson of Umea University as saying that 70-80% of care home residents admitted to geriatric hospitals with COVID-19 are sent back to the care home. Residents checked into the hospital with COVID19 were often sent back to the home, where of course the infection then spread.
  • He adds that in many cases they don’t die from COVID19 but from secondary infection with bacterial pneumonia, and could be saved with intravenous antibiotics. However, the prescribed care protocol for such patients is purely palliative — Morphin, Midazolam and Haldol – which according to him is a nearly 100% certain death sentence
  • A man named Thomas Andersson, who discovered that his father Jan, aged 81 had been put on this protocol (following diagnosis over the phone!) managed to get the decision reversed after first contacting the care home management, then going to the media. His father was put on an antibiotic IV and, once the bacterial pneumonia receded, managed to fight off the relatively mild COVID19 infection on his own. Below is Jan celebrating his recovery with children and grandchildren. Thomas still cannot believe such a thing was possible in Sweden.

Infuriating and appalling as such stories may be, they have a flip side: that if Sweden hadn’t gone “full Cuomo” on its elderly, its mortality might well have been a fraction of what they have now, and Sweden’s sonderweg might look a good deal better.

(2) Israel is, sadly, seeing a spike in new infections, almost all of them at a few schools in the Jerusalem area. Prof. Eli Waxman of the Weizmann Institute, who led the team that laid out Israel’s COVID19 planning,  discusses here how to handle a possible 2nd wave without lockdowns.

It sounds a lot like what  Norway envisages as its strategy for a second wave: individual test, track and trace as the first line of defense, where speed is of the essence; localized isolation measures as a second line of defense; expanding the ring of those if necessary; but national lockdown only as a very last resort. (It sounds like nobody in Israel, Norway, nor for that matter Belgium has any stomach for a second lockdown. This is especially true as Norway is wondering, with hindsight in numbers, if voluntary social distancing might night have been adequate. Your mileage may vary, of course — Norwegians and Italians, for example, would react very differently to strong social distancing recommendations.)

[…] In Israel, the HaMagen [“The Shield”] app, which was developed and endorsed by the Health Ministry and can tell people if they have been in the presence of anyone who has been diagnosed with coronavirus, could play a key role, he said. “The more people who download it, the better.” 
[In addition, the] Shin Bet [Israel’s domestic security service] was reported to have traced a third of Israel’s coronavirus cases, some 4,089 people, [through their cell phones.  Israel’s Supreme Court has however ruled that this cannot continue past the emergency order, unless anchored in law.]

[…] Waxman said South Korea has two advantages over Israel: It learned the importance of moving fast from its experience with Middle East Respiratory Syndrome (MERS) in 2015, when the virus killed 36 people, infected 186 and put thousands of citizens into isolation. The outbreak was ultimately traced to a single visitor from overseas. 
In addition, South Korea has leveraged some technological tools that “Israel cannot and should not be able to use” because they might infringe on privacy rights, he said.

 

(3) One “industry” which will be hit hard is higher education. Especially in the US, much of it is built upon an unsustainable base, with people paying extortionate tuition for amenities and administrative overhead that has nothing to do with education — be it the country-club level gym and dormitories, the football stadium (which only in a few places is net profitable), or the ever-expanding army of administrators. Now that these places were forced to move to distance learning, they found themselves competing with much cheaper online colleges. Instapundit has endlessly blogged (and written a book) about the “Higher Education Bubble” and the coming wave of creative destruction in that industry: COVID19 only accelerated a process waiting to happen. I had always assumed, however, that blue-chip brandnames like Harvard would be largely insulated. 

Now it turns out that not even Stanford (!) is fully immune, as revealed in a statement by the president

Many of our income streams will continue to be diminished: Housing revenue will be reduced due to fewer students living on campus; income-producing events and programs will continue to be limited; and clinical, research and philanthropic income streams will be challenged. At the same time, expenses in some areas, such as student financial aid, will increase. The market volatility affecting our endowment also can be expected to continue, given the seismic disruptions occurring in the national and global economies.

[…]

We previously asked university units to prepare FY21 budget plans based on a scenario with a 15 percent reduction in funding from endowment payout and a 10 percent reduction in support from general funds. We sincerely hope that the reductions needed will be smaller than this, but for now we need to plan to these targets as a contingency. We expect to provide final allocations of general funds and endowment payout to units by the end of June, enabling them to finalize their budgets in July.

As units plan for budget reductions, we expect there will be reductions in some of the programs each of them is able to offer. We will work to ensure that any program reductions still allow us to sustain Stanford’s core academic strengths and our long-standing commitments to student access.

Given the magnitude of the budget challenge, we also expect that program reductions will make some workforce reductions unavoidable as we enter the new fiscal year. We don’t yet know the scale of job reductions. We hope they will be limited, but they will be driven by the program needs and budget capacity of individual units. Our expectation is that some of these reductions will be temporary layoffs (furloughs) until we are able to resume services and bring employees back, and that other reductions will be permanent layoffs. At this time, we expect to be able to communicate more detailed decisions about layoffs in late July.

It would be too much to hope that the “programs” affected would primarily be silliness such as courses on “the poetics of the lowrider” (as Victor Davis Hanson has described elsewhere), rather than the STEM programs that made Stanford such a powerhouse. But never underestimate the reverse Midas touch of professional college administrators…. 

 

(4) And just because: “June came upon us much too soon…”

 

 

COVID19 update, May 31, 2020: which patients benefit most from Remdesivir; asymptomatic infection rate; the post-lockdown economy; miscellaneous updates

(1) Dr. Seheult discusses remdesivir for different categories of patients, and suggests that the drug is most beneficial (in terms of quicker recovery) for patients sick enough to require oxygen, but not so sick as to require mechanical ventilation or ECMOs (“heart-lung machines”). In this latter group, the virus has already done so much damage that remdesivir amounts to “closing the barn door after the horses have fled”, while mild cases will resolve on their own.

The conventional division of patients is (averaged across age groups):

  • 80% self-limiting, self-resolving disease
  • 15% get more severely ill
  • 5% critically ill

So it would be the 15% where the drug can make most of the difference, probably by keeping patients from moving into the 5% critical group. 

(2) Dr. John Campbell’s video looks at the asymptomatic infection rate, which he frustratingly places “between 5% and 80%”, and briefly highlights different studies that arrive at wildly different rates. My working assumption all along has been “about 50%”. 

(3) The Economist has a somewhat pessimistic take on the post-lockdown economy. Note that at least some of the economic effects of the pandemic are also felt in countries that never locked down, like Sweden.

Relatedly, Die Welt (in German) looks at how in reopened Germany, spending habits have changed to the extent that some retailers say they don’t see the point of reopening. The main shopping streets have seen foot traffic dwindle by 30 to 75% (Berlin’s famous Kurfürstendamm was hardest hit). Stores with an online presence, who kept in touch with customers during the crisis, have weathered the storm better, while some with a primarily online business model have seen revenue rise (including a new online grocery shopping chain).

(3) Miscellaneous updates:

Moderna’s COVID-19 vaccines now moves into Phase 2 clinical trials, reports the Jerusalem Post, who also note that the chief scientific officer of Moderna is an expat Israeli. (Like in information technology, tiny Israel punches well above its weight in biotech.)

Forbes highlights what it calls the most important COVID-19 statistic: 42% of US deaths occur in a group that is just 0.6% pf the US population, namely care home residents.

Oddly enough: Monkeys steal COVID-19 testing samples in India. 

Tangentially related, the Daily Telegraph looks at what awaits Hong Kong under full ChiCom rule. The UK has offered asylum to Hong Kongers who still hold BNO (British National Overseas) passports. (This unusual type of passport does not come with automatic “right of abode” in the UK.)

COVID19 update, May 30, 2020: Fang Fang’s “Wuhan Diary”

The Chinese novelist Fang Fang has lived most of her life in Wuhan, going back to the days before the Cultural Revolution. Until her retirement, she used to be the provincial chair of the Chinese Writers Association. 

(Wuhan, the capital of Hubei province, was originally three separate cities named Wuchang, Hankou and Hanyang, all lying on the confluence of the Han and Yangtze rivers.)

When it became clear that an epidemic was breaking out, she started writing diary entries and posting them  on Chinese social media. They quickly acquired a following in the millions, despite furious attempts of online censors to airbrush them away. By the time the lockdowns on Wuhan were lifted, the combined diary had reached book length.  

Now translations in both English and German have come out. I read the English translation, which is available on Amazon. The rating is dragged down by a number of 1-star reviews posted by obvious “50-Cent Army” troll reviewers. So I decided to read the book for myself.

I warmly recommend it, despite its high price ($19.99). It is a unique first-person document by an articulate person with lots of contacts, including in the medical system.

It seems that the Wuhan residents were just as bamboozled by the ChiCom regime as the West. Doctors at the Central Hospital apparently realized early on that they were not just dealing with a new SARS-like infection, but that it was contagious person-to-person. After attempted whistleblower  Dr. Li Wenliang was strong-armed by the police into confessing he had been spreading false news, the others apparently restricted themselves to quietly warning each other. Yet officials eventually realized something was up and organized a high-level meeting on the 14th, which ended inconclusively. Even the Chinese New Year celebration was allowed to proceed.

She tells numerous stories of friends, acquaintances, and relatives who succumbed to the disease — many of them surprisingly young. Many medical personnel (including Li Wenliang) were among the early casualties, but also such people as journalists and cameramen.

She also relates the harrowing period where the local medical system was overwhelmed and patients would die while waiting to be admitted. This was a brief situation, alleviated when medical personnel and supplies started flowing in from other parts of China. 

She highlights the inventiveness of the locals in coping with the lockdowns and the attendant logistical problems. For example, as trying to shop individually was problematic (you were allowed out of your apartment complex once every 3 days) and often stores could not handle the flood of calls, an informal association of residents would collect orders, place a centralized bulk order, then distribute the ordered grocery parcels, at first by placing them in the building’s courtyard, then by placing them in buckets lowered from the windows of residents.

Food donations from other parts of China were apparently abundant enough that distributing them before they spoiled became a problem. She proposed a surprisingly (or not) “capitalist” solution: deliver to grocery stores (who have the storage and the delivery network in place), and let them resell at highly discounted prices meant to cover their distribution costs. 

While she affirmed the necessity of a strict lockdown, she highlights a number of instances where unthinking and callous enforcement of the letter of regulations, with no room for common sense, led to suffering and deaths. (One example that stands out in my mind was a special-needs child left to fend for itself when its father was placed in isolation. Another was a married couple stuck on a bridge between two boroughs because the two spouses had residence permits for opposite banks of the river.) 

“People often have reasons that they use to describe their actions, such as “we were just carrying out written directives.” But reality is filled with all kinds of unpredictable changes, whereas written directives are often prepared hastily with only broad guidelines. Moreover, those written directives are mostly composed with common sense in mind, so they are usually not in direct contradiction with the basic principles of humanitarianism. All we need is for the people assigned to enforce these principles to have just a little more humanistic spirit; just enough so that a driver who had been stuck out on the highways for more than 20 days wouldn’t end up with his life in danger; just enough so that when someone is infected with coronavirus, a crowd of people doesn’t end up sealing their front door with a steel rod so that everyone is locked inside; just enough so that when an adult is forced into mandatory quarantine, their children don’t end up starving to death alone at home. That is all I am asking for.”

Some of her tales will sound familiar — for example, how the suspension of all non-emergency medical services at the height of the epidemic led to other medical problems being neglected (e.g., dialysis and chemotherapy cases). (Apparently she and two of her siblings are diabetic, and the siblings have additional chronic medical problems, so this is something they experienced first-hand. Her ex-husband caught COVID but survived.) 

She also described, via her medical contacts, that mortality at the hospitals decreased once the capacity crunch was over and the doctors had refined their treatment protocols. She mentions remdesivir being applied with some success: non-intubated patients were also often treated with traditional Chinese remedies alongside Western medicine. She herself took various herbal potions in an attempt to boost her immune system. 

Telling it like it is, warts and all, earned her enemies, and even death threats.

“Today there is something I want to get off my chest that has been weighing on me for a long time: Those ultra-leftists in China are responsible for causing irreparable harm to the nation and the people. All they want to do is return to the good old days of the Cultural Revolution and reverse all the Reform Era policies. Anyone with an opinion that differs from their own is regarded as their enemy. They behave like a pack of thugs, attacking anyone who fails to cooperate with them, launching wave after wave of attacks. They spray the world with their violent, hate-filled language and often resort to even more despicable tactics, so base that it almost defies understanding.”

In a footnote, she explains that by ultra-leftists she means ultra-Maoist nostalgics for the Cultural Revolution era, opposed to the reformist polices introduced by Deng Xiaoping.  These people report her posts on the Chinese Twitter-clone and managed to get her account blocked a number of times.

In this atmosphere, newspapers practice self-censorship. She highlights the story of a man who left a testament of 11 word, “I donate my body to the state… what about my wife?” where the newspaper would only highlight the first seven words as concern for his surviving spouse was apparently not worthy of sharing the limelight with his selfless devotion to the state.

(She does mention that autopsies of people like that man were invaluable in helping doctors understand what they were dealing with, notably the ARDS.)

The party leadership and officialdom — well, let me quote her:

“The world of officialdom is filled with people who have never learned a damn thing in their entire lives, but one thing they have mastered is the art of putting on a show; and they have ways to deal with you that you would have never imagined even existed. Their ability to shirk responsibility is also second to none; if they didn’t have a good foundation in all these worthless skills, this outbreak would have never grown into the large-scale calamity that it is today.”

She mentions that three groups of specialists had come to visit during the earlier stages of the outbreak. The first two had accepted the claim that no person-to-person transmission took place, but the leader of the 3rd group —  one Dr. Zhong Nanshan, who had earned his spurs in managing the original SARS outbreak — did not take no for an answer. Under insistent questioning, it was admitted that a patient had infected 14 others, and he announced on January 20 that person-to-person transmission did take place. By then, of course, precious time had been lost.

 

 

 

 

COVID19 update, Shavuot edition: Singapore research finds 50% of sample has pre-existing immunity

Breaking news (via Instapundit): Prof. Francois Balloux from UCLondon highlights preprint from Singapore: https://doi.org/10.1101/2020.05.26.115832

Recent preprint reporting that 24/24 (100%) people form Singapore infected by SARS-1 in 2003 have pre-existing T-cell immunity against #SARSCoV2, but more surprisingly 9/18 (50%) with no exposure to SARS-1 also possess T-cells targeting #SARSCoV2.

One take[-]home message is that infection with coronaviruses induces strong and long-lasting T-cell (cross-)immunity. T-cell immunity is likely a far more important for our immune response to #SARSCoV2 infection than antibodies, in line with other recent reports.

What remains unresolved is which virus caused T-cell immunity in the people with no prior exposure to SARS-1 in 2003. We know of seven coronaviruses infecting humans: #SARSCoV2, SARS-1, MERS and four causing ‘common colds’ (OC43, HKU1, 229E and NL63). [NB: most common colds are caused by rhinoviruses, which are a different family]

Intriguingly, none of the known viruses in circulation in humans looks like a good candidate for the T-cell immunity to #SARSCoV2 in those with no prior exposure to SARS-1. This might suggest that other yet unknown coronaviruses could have been in circulation in humans.

No surprise that having had SARS 1.0 would protect you against SARS 2.0, but nice to know. But that half of a random sample would have immunity owing to previous exposure to a common cold-level virus… If confirmed on a larger sample, this could be yuge. Put this together with the 2nd-order correction for the herd immunity threshold, and acquiring herd immunity could take a lot less doing than previously assumed…

Developing…

Happy Shavuot to my fellow Jews!

UPDATE 1: Dr. Anthony Fauci no longer considers 2nd wave inevitable.

“We don’t have to accept that as an inevitability. Particularly[…] when people start thinking about the fall. I want people to really appreciate that, it could happen, but it is not inevitable.”

COVID19 update, May 28, 2020: ACE inhibitors beneficial; asymptomatic infection rate as high as 80%; NYT on California economy in freefall

(1) The lead story of Chemical and Engineering News, the house organ of the American Chemical Society, is about rethinking the role of ACE inhibitors (angiotensin converting enzyme inhibitors, a commonly used family of blood pressure drugs).

https://cendigitalmagazine.acs.org/2020/05/22/rethinking-the-role-of-blood-pressure-drugs-in-covid-19/content.html

“Once thought to boost levels of ACE2 , the novel coronavirus’s doorway into human cells, these widely used medicines are now contenders to treat the respiratory disease”

(2) Meanwhile,  the Daily Telegraph has a popular write-up of an intriguing paper that just appeared in Thorax, a daughter journal of the British Medical Journal. It suggests the asymptomatic infection rate may be much higher than the 35% in the revised CDC figures

http://doi.org/10.1136/thoraxjnl-2020-215091

ABSTRACT: We describe what we believe is the first instance of complete COVID-19 testing of all passengers and crew on an isolated cruise ship during the current COVID-19 pandemic. Of the 217 passengers and crew on board, 128 tested positive for COVID-19 on reverse transcription–PCR (59%). Of the COVID-19-positive patients, 19% (24) were symptomatic; 6.2% (8) required medical evacuation; 3.1% (4) were intubated and ventilated; and the mortality was 0.8% (1). The majority of COVID-19-positive patients were asymptomatic (81%, 104 patients). We conclude that the prevalence of COVID-19 on affected cruise ships is likely to be significantly underestimated, and strategies are needed to assess and monitor all passengers to prevent community transmission after disembarkation.

The Uruguayan Ministry of Health provided on board SARS-CoV-2 virus testing of all passengers and crew, which occurred on 3 April (day 20; Atgen-Diagnostica, Montevideo) with CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel.

In the body text we find that: 

 

[The 128 who tested positive on RT-PCR]  included all passengers who tested negative on the VivaDiag qSARS-CoV-IgM/IgG Rapid [antibody] Test. There were 10 instances where two passengers sharing a cabin recorded positive and negative results.

[…]

From the departure date in mid-March 2020 and for the next 28 days, the expedition cruise ship had no outside human contact and was thus a totally isolated environment in this sense. […]

[…]

We conclude from this observational study that

  • The prevalence of COVID-19 on affected cruise ships is likely to be significantly underestimated, and strategies are needed to assess and monitor all passengers to prevent community transmission after disembarkation.
  • Rapid  [antibody] COVID-19 testing of patients in the acute phase is unreliable.
  • The majority of COVID-19-positive patients were asymptomatic (81%).
  • The presence of discordant COVID-19 results in numerous cabins suggests that there may be a significant false-negative rate with RT-PCR testing. Follow-up testing is being performed to determine this.
  • The timing of symptoms in some passengers (day 24) suggests that there may have been cross contamination after cabin isolation.

 

Just how reliable is RT-PCR really?  According to this piece in IEEE Spectrum, current test setups reach are essentially 100% sensitive (no false negatives) and 96% specific (4% false positives) with lab-generated samples., i.e., if you feed them virus cultures. The trouble begins when you have to collect specimens from actual patients.  According to this piece in MD Magazine,   “Of the specimens collected [from known COVID-19 patients], bronchoalveolar lavage fluid specimens demonstrated the highest positive rates of at 93% (n = 14). This was followed by sputum at 72% (n = 75), nasal swabs at 63% (n = 5), fibrobronchoscope brush biopsy at 46% (6/13), pharyngeal swabs at 32% (n = 126), feces at 29% (n = 44) and blood at 1% (n = 3). The authors of that study pointed out that testing of specimens from multiple sites may improve the sensitivity and reduce false-negative test results.” 

 

(3) Via David Bernstein: the WSJ on New York’s long road to recovery even after a lifting of the lockdown. (Archived copy here.)

And via Instapundit, the NYTimes on The price of a lockdown: economic freefall in California

(archived copy ) To be fair, the tourism industry would have been bludgeoned with or without a lockdown, as the (proportionally less important) Swedish tourism sector has learned.

But a large part of the rest could have been mitigated, and can still be mitigated, by not going the “37-step reopening over 10 years” route in California.  (Heck, when did The Babylon Bee forget it was a satirical publication?) But — as much as this sickens even the jaded student of history — I suspect that for some politicians, ensuring that the recovery does not happen before November is worth any price…  

 

Finally, to my Jewish readers, happy Shavuot! There will probably not be an edition on the holiday unless breaking developments warrant it.

 

ADDENDUM: an op-ed in The Lancet in defense of prophylactic use of hydroxychloroquine in India.

COVID19 update, May 27, 2020: Norwegian official report now questions necessity of lockdown; Dr. John Campbell on The Lancet hydroxychloroquine study

 

(1)  According to the Spectator (UK), a report (in Norwegian) by the Norwegian public health authority now argues their lockdown was probably unnecessary as voluntary social distancing efforts were already effective enough.

Norway is assembling a picture of what happened before lockdown using observed data – hospital figures, infection numbers and so on – to assess the situation in the country in March. At the time, no one really knew. It was feared that Covid was rampant with each person infecting two or three others – and only lockdown could stop this exponential growth by cutting the R number to 1 or lower. But the country’s public health authority has published a report with a striking conclusion: the virus was never spreading as fast as had been feared and was already on the way out when lockdown was ordered. ‘It looks as if the effective reproduction rate had already dropped to around 1.1 when the most comprehensive measures were implemented on 12 March, and it would not take much to push it down below 1… We have seen in retrospect that the infection was on its way out.’

This raises an awkward question: was lockdown necessary? Could voluntary social distancing alone have achieved the same outcome? Camilla Stoltenberg, director of Norway’s public health agency, has given an interview where she is candid about the implications of this discovery. ‘Our assessment now, and I find that there is a broad consensus in relation to the reopening, was that one could probably achieve the same effect – and avoid part of the unfortunate repercussions – by not closing. But, instead, staying open with precautions to stop the spread.’ This is important to admit, she says, because if infection levels rise again – or a second wave hits in the winter – you need to be brutally honest about whether lockdown proved effective.

Norway’s statistics agency was also the first in the world to calculate the permanent damage inflicted by school closures: every week of classroom education denied to students, it found, stymies life chances and permanently lowers earnings potential. So a country should only enforce this draconian measure if it is sure that the academic foundation for lockdown was sound. And in Stoltenberg’s opinion, ‘the academic foundation was not good enough’ for lockdown this time. The leading article in the new Spectator, out tomorrow, argues that Britons deserve the same candour.

I don’t have enough Norwegian to read the entire report: I will try to get a contact there to help me out. A member of our own ad hoc commission described the situation around the time as “fog of war” (ar`afel krav) — I can understand that, with incomplete information, the Norwegians made the decision they did. (They also had more economic ‘buffer capacity’, as it were, to absorb the economic blow than many others. Their mortality statistics are just 235 dead out of a population of 5.3 million.) 

I would like to venture, however, that “to lockdown” or “to go Swedish”  is a false binary choice. Norway is a very large country with vast differences in population density: I see no intrinsic reason why greater Oslo, for example (and perhaps Bergen and Trondheim) could not have been subjected to a lockdown separately from a more laissez-faire approach for the rest of the country.

Norway started reopening shortly after us — and no, the sky hasn’t fallen there. (We ourselves reopened cafés and sit-down service in restaurants  today, pretty much everything else already being open.)

(2) Dr. John Campbell discusses hydroxychloroquine, the initial encouraging results from clinical trials, and then finally the recent multinational registry analysis published in The Lancet

https://doi.org/10.1016/S0140-6736(20)31180-6

that indicates hospital survival rates are actually lower on HCQ or CQ than without, and that the gap increases when a macrolide antibiotic such as azithromycin is added (presumably owing to heart arrhythmias). Dr. Campbell is clear that neither this study (nor the earlier ones) include zinc supplementation, which would seem to be a fatal flaw.

Collateral results from this very large sample are confirmations of statistical correlation between severity of  COVID19 and factors such as obesity, recent smoking, diabetes, being male, hypertension,… and black or Hispanic ancestry (he again stresses increased propensity for vitamin D deficiency). More surprising was the finding that East Asians (i.e, Chinese, Japanese, and Koreans) appear to be less vulnerable than Caucasians. Taking ACE inhibitors (but not angiotensin receptor blockers) also appears to be correlated with reduced severity, as is taking statins.

(3) For what it’s worth, the CDC website has an aggregator page of the various COVID19 epidemic models. “All models are wrong, but some are useful” (George E. P. Box FRS) — the useful ones now may be those that fit their parameters to the observed time evolution of data.

And while only tangentially COVID19 related, the Jerusalem Post reports on the controversy regarding the tender for building “the largest desalination plaint in the world” Sorek-2 in Israel. The Chinese were poised to win the tender, but following US pressure applied during SecState Mike Pompeo’s visit, an Israeli consortium won out instead. 

 

ADDENDUM: Via commenter “No More Obamas” on Instapundit , here is an article in the Sydney Morning Herald on the Australian lockdown decision 

Australia’s policymakers were in March bracing for up to 150,000 deaths from the coronavirus pandemic as the virus spread globally and health officials warned that hospitals might not be able to cope.

Ten weeks later, with just 103 COVID-19 deaths, some experts say the modelling behind the national cabinet’s decisions was flawed and some commentators say the response went too far.

[…] On Tuesday Chief Medical Officer Brendan Murphy told the Senate inquiry into the Morrison government’s response to the pandemic that Australia had avoided 14,000 deaths by implementing strict social distancing measures, considerably fewer than the initial warning.

COVID19 update, May 26, 2020: Sweden revisited; homes for the elderly; new drug on the block

(0) Israel today celebrated its first day with zero new cases.

(1) Via Instapundit, SSRN (Social Science Research Network, a preprint server similar to arXiv.org, medrxiv.org, biorxiv.org and chemrxiv,org) has a article in press about the Swedish COVID19 epidemic. 

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3609493

Their per capita death rate is an order of magnitude larger than neighboring Scandinavian countries. It is tempting to attribute all this to Sweden’s Sonderweg (“road alone”) — but this article makes a case that at least part results from factors unrelated to Sweden’s decision not to go on lockdown.

Not only is half of Sweden’s mortality concentrated in just the capital city Stockholm, but over 70% of Sweden’s mortality is in nursing homes. As the article explains, in Sweden the elderly tend to stay at home for as long as possible, assisted by home helpers assigned by the public healthcare system. (Independent assisted living facilities do exist, apparently mostly in the private sector.) But normally a home for the elderly is a last-resort option, and those who move in there are generally so frail that their median stay there is under one year. (Such facilities in Sweden have doctors etc. on site.)

Now in a facility where everybody needs a lot of hands-on care, there is plenty of room for nosocomial (i.e., caregiver-transmitted) infections unless staff is (a) healthy and (b) has extensive training and/or experience in biosafety. Guess who does the most “hands-on” work at such care homes? First-generation immigrants from the Third World, often with at best high school education. And guess what else? Immigrants are the second most common group of COVID19 victims in Sweden, after the elderly. 

Immigrants tend to live in crowded conditions, and many probably have  major issues with vitamin D deficiency (and hence a weakened immune system) in winter. (Even light-skinned “Vikings” would be in trouble in a sub-arctic winter, were it not that Scandinavians tend to fortify their diet with vitamin D supplements — I was floored once to see cod liver oil at a hotel breakfast buffet!)

Intriguingly, overall year-over-year mortality is not as elevated as you might expect — COVID19 mortality was compensated in part by an unusually mild flu season.

Now Sweden is just an egregious example of a general trend: Steve “Vodkapundit” Green points out that  42% of Americans whose deaths have been attributed to COVID-19 were in nursing homes or assisted living centers. 

He links to a report of the International Long-Term Care Policy Network about deaths in such facilities in a number of countries. A few quotes:

On the 3rd of May there had been 7,844 deaths linked to COVID-19 in Belgium, of these, 4,164 people died in care homes (53%). The report also includes suspected cases and, of the total deaths, 83% of all care home deaths were suspected cases, and only 17% had been confirmed. The reported % of deaths in care homes has increased since the first date these data were published, from 42% on the 11th April to 53% on the 3rd May. The report also contains data on the numbers of care home staff and residents that have been tested since the 10th of April. As of May 3, 88,883 staff were tested, of these, 3% were positive, and of those who tested positive, 72% were asymptomatic. Of the 68,336 residents who had been tested, 7% were positive and of these, 74% were asymptomatic.

[…] In British Columbia[, Canada], counts published by the BC Centre for Disease Control11 on May 1 illustrate a total of 112 deaths as a result of COVID-19, of which 70 (63%) were patients/residents in care facilities, which includes acute care institutions, long-term care homes, assisted and independent living establishments. On that day, there were a total of 2,145 confirmed cases of COVID-19 in the province, of which 260 (12%) were patients/residents in these establishments. 

[…] In Ontario[…] The official report included a total of 1,216 deaths as a result of COVID-19, of which 590 (49%) were residents in long-term care homes.

[…] Quebec is the province with the highest cases and the most deaths related to COVID-19 in Canada. According to the most up-to-date estimates from both governmental and media releases on April 29, a total of 1,859 deaths as a result of COVID-19 occurred in the province, of which 1,469 (79%) were residents in long-term care homes. Tabarnak!

[…] The total deaths in Germany on the 3rd May were 6,649, so deaths in communal settings represent 36% of all deaths (36.5% including mortality of staff in communal settings)24. […]

The first COVID-19 patient in Israel was diagnosed on February 27th and since then the number of confirmed cases has risen to 15,782 (as of April 29th), with 120 in serious condition and 202 deaths. Of the deaths, 65 were long-term care residents (32%).

[…] According to their data of the 3rd May41, the total number of deaths in nursing homes is 16,878, which, according to this source, adds up to 67% of all deaths by COVID-19 in Spain. The greatest number of deaths happened in Madrid (5,828) and Catalonia (3,044). […]

 

 

Figure1

(2) Via the Jerusalem Post, here is a preprint from the Israel Institute for Biological Research

https://doi.org/10.1101/2020.05.18.103283

indicating that an analogue of Cerdelga (Eliglustat), a drug for the rare metabolic disorder named Gaucher’s Disease, might be a useful broad-spectrum antiviral. From the abstract:

Since viruses are completely dependent on internal cell mechanisms, they must cross cell membranes during their lifecycle, creating a dependence on processes involving membrane dynamics. Thus, in this study we examined whether the synthesis of glycosphingolipids, biologically active components of cell membranes, can serve as an antiviral therapeutic target. We examined the antiviral effect of two specific inhibitors of GlucosylCeramide synthase (GCS); (i) Genz-123346, an analogue of the FDA-approved drug Cerdelga®, (ii) GENZ-667161, an analogue of venglustat which is currently under phase III clinical trials. We found that both GCS inhibitors inhibit the replication of four different enveloped RNA viruses of different genus, organ-target and transmission route: (i) Neuroinvasive Sindbis virus (SVNI), (ii) West Nile virus (WNV), (iii) Influenza A virus, and (iv) SARS-CoV-2. Moreover, GCS inhibitors significantly increase the survival rate of SVNI-infected mice. Our data suggest that GCS inhibitors can potentially serve as a broad-spectrum antiviral therapy and should be further examined in preclinical and clinical trial. Analogues of the specific compounds tested have already been studied clinically, implying they can be fast-tracked for public use. With the current COVID-19 pandemic, this may be particularly relevant to SARS-CoV-2 infection.

 

(3) Miscellaneous:

Charlie Martin about YouTube censorship of comments about the “Fifty-Cent Army” (the paid internet commenter brigade of the CCP). 

DIE WELT refers to Angela Merkel’s silence in the face of China’s repression of Hong Kong as “Merkel’s kow-tow”.

Elsewhere, the German paper reports on the “nightmarishly” empty beaches in St.-Tropez on the French Azure Coast. Now any tourist would be welcome — not just the rich and famous — but they aren’t coming. It would seem obvious that tourism is one sector of the economy that was going to get near-fatal blows with or without lockdowns.

According to the Daily Telegraph, remdesivir will be rolled out in the UK for treatment. 

COVID19 update, US Memorial Day edition: meat-packing plants as hotspots around the world; Japan lifts state of emergency; Philippines in longest lockdown anywhere; Robert A. Heinlein for Memorial Day

(1) A reader drew my attention to a COVID19 outbreak in Nobles County, Minnesota — again linked to a meatpacking plant (JBS, in this case). According to a May 12 report from MPR (Minnesota Public Radio), https://www.mprnews.org/story/2020/05/12/latest-on-covid19-in-mn

In southwestern Minnesota’s Nobles County, where an outbreak hit Worthington’s massive JBS pork plant, about 1 in 17 people have tested positive for COVID-19. In mid-April, there were just a handful of cases. On Tuesday, there were 1,291 confirmed cases. The numbers were still increasing, although at a slower rate than in previous weeks. [Ed.: My source adds: now 1,414 positive cases out of a county population of 21,378, about 6.6% or one in fifteen. So far, there have only been 2 deaths.]

The JBS plant shut on April 20 but has partially reopened with expanded hygiene and health monitoring measures.

Similar problems have been reported in Stearns County, where COVID-19 cases tied to two packing plants — Pilgrim’s Pride poultry plant in Cold Spring and Jennie-O Turkey in Melrose — have skyrocketed. An undisclosed number of workers at both plants have tested positive for the virus.

There were about 55 confirmed cases in Stearns County two weeks ago. By Tuesday, confirmed cases had jumped to 1,512.

The Grauniad has more on US meat-packing plants. 

But this is not just a US thing. We noted several outbreaks at meat packing plants in Germany — earlier we offered a translation of an interview with an anonymous Polish worker in one such plant. In brief: work in very close quarters (2ft/60 cm. between stations) in enclosed, air-conditioned spaces; the line laborers are mostly guest workers (there from Poland, Romania,…) who sleep two to a room or even four to a room in “accommodation” arranged via the subcontractor; … 

And Australia had an outbreak near Melbourne (hat tip: Wannita F.)

 

(2) Japan is apparently lifting its state of emergency even in Tokyo, 

In contrast, the Philippines has been under possibly the longest lockdown anywhere, longer even than Wuhan reports DIE WELT. which also quotes President/strongman Duterte as saying quarantine violators should be shot.Here is a drier report in English in US News and World Report has some detail in English. : it is clear that, in a country where many people already eke out a precarious existence at the best of times, their loss of their meager income quickly brings on actual hunger. 

(3) I thought of a suitable quote for US Memorial Day. Then I figured I could add nothing to the words of Robert A. Heinlein in The Pragmatics Of Patriotism — his 1973 Forrestal Lecture at the US Naval Academy, Annapolis (of which he himself was an alumnus — he started writing after being invalided out of the US Navy). The full text is available online here. I cannot help being moved everytime I read it, especially the peroration:

The time has come for me to stop. I said that ‘Patriotism’ is a way of saying ‘Women and children first.’ And that no one can force a man to feel this way. Instead he must embrace it freely. I want to tell about one such man. He wore no uniform and no one knows his name, or where he came from; all we know is what he did.

In my home town sixty years ago when I was a child, my mother and father used to take me and my brothers and sisters out to Swope Park on Sunday afternoons. It was a wonderful place for kids, with picnic grounds and lakes and a zoo. But a railroad line cut straight through it.

One Sunday afternoon a young married couple were crossing these tracks. She apparently did not watch her step, for she managed to catch her foot in the frog of a switch to a siding and could not pull it free. Her husband stopped to help her. But try as they might they could not get her foot loose. While they were working at it, a tramp showed up, walking the ties. He joined the husband in trying to pull the young woman’s foot loose. No luck.

Out of sight around the curve a train whistled. Perhaps there would have been time to run and flag it down, perhaps not. In any case both men went right ahead trying to pull her free… and the train hit them. The wife was killed, the husband was mortally injured and died later, the tramp was killed – and testimony showed that neither man made the slightest effort to save himself. The husband’s behavior was heroic… but what we expect of a husband toward his wife: his right, and his proud privilege, to die for his woman. But what of this nameless stranger? Up to the very last second he could have jumped clear. He did not. He was still trying to save this woman he had never seen before in his life, right up to the very instant the train killed him. And that’s all we’ll ever know about him.

THIS is how a man dies. This is how a man lives!

‘They shall not grow old as we that are left grow old;
age shall not wither them nor the years condemn;
At the going down of the sun and in the morning, we shall remember them”

– Tomb of the Scottish Unknown Soldier, Edinburgh