COVID19 update, July 30, 2020: Cross-immunity, or: Does a past common cold protect against COVID19?

Most common colds are caused by rhinoviruses — a different family — but about 15% are caused by coronaviruses. “Cross-immunity” is where past infection (and acquired immunity) against one virus in a family gives you partial or complete immunity against other viruses in the family (e.g., because your immune system got “trained” to a part of the virus common to the entire family, such as the coronavirus “spikes”).
DIE WELT has a long interview (in German) with a pulmonologist at the Charité Hospital in Berlin. Below are some highlights in (very slightly edited) machine translation, thanks to the awesome DeepL.com.

[…]WELT: In April, they made a very astonishing discovery in the laboratory: 40 percent of the volunteers they tested who had never come into contact with the corona virus before had cells in their blood that the virus was able to fend off. What exactly does this mean?
Leif Sander: At first, we were amazed by the findings ourselves. But apparently a previously experienced infection with related corona viruses activates the immune system in such a way that it also reacts to sars-CoV-2.
WELT: What does this activation look like?
Sander: The immune system consists of two systems: In one system antibodies are produced, i.e. proteins that can recognize an invading pathogen and eliminate it if possible. The second system is the cellular immune response. This produces so-called T-cells, which can either help other cells to render the pathogen harmless, or which can also attack it directly. In further experiments we have now been able to show that these T-cells apparently originate from previous cold corona infections. The common cold has given people immune cells that also recognise the new corona virus.
WELT: Does this mean that people who previously had a cold are now protected from Covid-19?
Sander: Unfortunately, we do not know. Based on our findings and similar studies from other laboratories, we have put forward the hypothesis that 30 or 40 percent of all people have cross-immunity. But this is only a hypothesis. In the laboratory we see that the activated T-cells are able to recognise sars-CoV-2 viruses. Do you think this also leads to protection against infections in living humans? In order to prove that, one has to do large studies. At the beginning of the study, the blood of volunteers would have to be searched for T-cells from previous coronavirus infections. And then it would have to be observed whether people with this existing immune trait become infected less frequently or at least become less seriously ill. Such a study was initiated by my colleague Andreas Thiel at the Charité. The study will, for example, examine the immune status of educators, residents of nursing homes and other institutions.

[…]

WELT: With the rhinitis corona viruses the immune protection does not last very long.
Sander: That is true, recently a large study has shown that a reinfection with these viruses is possible after only one or two years. The antibody concentrations in the body decrease rapidly. Maybe this is also due to the fact that rhinitis corona viruses do not make people particularly ill, which means that the immune system is not activated as strongly.
WELT: Could this also be the case with infections with the new corona virus? So that only those who are seriously ill – those who have no symptoms or only mild symptoms but no protection – build up good immune protection?
Sander: That could be, yes.
WELT: Does cross-reactivity mean that we have less to fear about the further course of the pandemic? After all, a part of the population would then be a little bit protected …
Sander: No, the basic assessment does not change at first. Cross-immunity is not a new addition – it has existed in the population from the very beginning. But if it really protects against severe disease progression or even infections, that would be good news.

WELT: In your work you concentrate on the T-cell response. However, these cells hardly play a role in the public discussion about immunity. There is always talk about antibody tests. What is more important for long-term protection – antibodies or immune cells?
Sander: You can’t say that in general. For some infections, antibodies play a more important role for the immune protection, whereas for other T-cells they play a more important role. Antibodies are easier to detect, there are also rapid tests for this. T-cells are more complicated to handle, you need blood samples and special laboratories. The immune system is extremely complex – and sometimes very surprising. For example, textbooks say that measles protects those who have a certain concentration of antibodies in their blood from infection. However, there are also people who are unable to produce measles antibodies due to a rare disease – but who are nevertheless protected. This is probably where T-cells provide protection. Whether we need antibodies, T-cells or even both for protection against the new coronavirus is not clear.
WELT: If one is optimistic and assumes that after an infection a medium-term sustained immune protection is built up and that perhaps even many people are already protected thanks to cross-immunity, could we still achieve herd immunity?
Sander: If most of the sick people would build up a good and lasting immune protection, as is the case with measles, then it could work. If this is not the case, as with rhinitis, then it doesn’t work. We know too little to give a conclusive answer to this.
But it is more important to know that in order to build up herd immunity, we would have to take the risk of many infections and also severe courses. Nobody can want that. The lockdown bought us time, which we should now invest in research into the correct handling of the virus. Establishing natural herd immunity would probably not be the right strategy. Rather, I am banking on a multi-layered approach with herd immunity achieved through vaccination.

Tisha be-Av post: Raul Hilberg’s studies on the role of German railways in the Shoah

Today is Tisha be’Av (9th of Av), the day when practicing Jews commemorate a long litany of calamities, of which the Destruction of the First and Second Temples and the 1492 Gerush Sefarad (Spanish Expulsion) are but the best-known ones. (In general history, August 1-2, 1914, or 9-10 Av, 5764 also happens to be the date on which Germany entered World War One.)

The date has at least two links to the Shoah (Holocaust) that I can think of:

(a) August 2, 1941 (9 Av, 5701): two days earlier, Göring’s infamous letter charging Heydrich to “submit to me soonest, a comprehensive plan for the organizational, practical, and material preparations for the sought-after Final Solution of the Jewish Question“. [To the best of my knowledge, this is the first time the phrase Endlösung der Judenfrage]

(b) July 23, 1942 (9 Av 5702):  the first deportation trains leavethe Warsaw Ghetto for the extermination camp Treblinka.

In fact, some religious Jews (and Menachem Begin z”l, who had lost his parents and brother in the Shoah and had himself escaped by the skin of his teeth) objected to the creation of a separate Yom HaShoah, and instead wanted to commemorate it on Tisha Be’Av. 

While I did not observe a full fast this year due to COVID19,  I took a “yom bechira” (optional day off) as is my wont, and spent it reading material appropriate to the sadness of the day. I just finished this book:

The centerpiece of the collection are two essays by Raul Hilberg, written in his vintage style: a dry, pitiless barrage of facts that eschews philosophical reflection on the “why” in favor of painstaking document research into the “how”. But the pieces by Christopher Browning and Peter Hayes add a lot. Some things I learned from this collection:

(a) it is received wisdom that the Nazis (y”sh) shortchanged their own troops in their obsession to free up trains for transporting Jews to their death. In fact, as the authors lay out in great detail, the death camp trains accounted for about 0.7% of all the capacity in the network, and the rolling stock used were often ramshackle, decommissioned railway cars (usually boxcars) that had been kept at marshaling yards for emergencies rather than sent to the scrap heap. 

There were indeed pauses in the deportations when every bit of network capacity in Poland was needed, such as in the autumn of 1941 during Operation Typhoon (the Wehrmacht’s push for Moscow).  

(b) The degree of cooperation on the part of the Reichsbahn was absolutely astonishing. Anybody who was paying attention would have understood that these people were not merely being “resettled”. But most chose to look away and to focus instead on the logistics of most efficiently slotting these “DA” trains (as they appeared in logistics documents: DA=Deutsche Aussiedler, German emigrants).

Indeed, creative logistics were applied throughout: for example, goods trains that had delivered military supplies to the garrison in Greek Macedonia, and otherwise would have returned empty, made the return trip with Jews from Thessaloniki who were brought to Auschwitz.

The Reichsbahn indeed charged the RSHA for these trains, at the 3rd class passenger rate, with 50% discount under age 10, and free under age 4. (Never mind they were not even providing 4th-class carriages but box cars.) For special trains, a group discount was applied for 400 passengers and up. The RSHA, with typical cynicism, extorted the transport costs from the Jewish community or squeezed the hapless “passengers” themselves.

If the Reichsbahn bothered to provide any comfort at all, it was to the guards (who typically got a 2nd class car for their usage when not on watch).

(c) For a variety of reasons, nearly nobody in the Reichsbahn was ever punished. The CEO, who wore a second hat as Transport Minister, died from cancer just after the war. His deputy, Albert Ganzenmüller, fled to Argentina but returned ten years later, and a later prosecution against him was eventually suspended due to (real or feigned) mental deterioration of the defendant.

Lower-level officials and technical personnel found themselves desperately needed by the Allies to get the railway network back to working condition again — which they did with the same efficiency with which they had earlier acquitted themselves of their most grisly work.

That old saw “to understand all is to forgive all” is a load of tripe. Some things, the more you understand, the more you loathe them.

(Robert A. Heinlein, “Starship Troopers”)

COVID19 update, July 29, 2020: Second wave in Europe; eyeing a new Roaring Twenties post-pandemic; Israeli ‘coronavirus czar’ unveils new plan of action

(1) In this video, Dr. Campbell is being interviewed by a reporter from the Deutsche Welle’s English-language service.

(2) In the Daily Telegraph, this piece [UPDATE: archive copy without paywall] looks at the aftermath of the 1918 “Spanish Flu” pandemic and the roaring economic surge that followed it — and predicts the same will happen now, even if the COVID19 epidemic is both much less deadly and economically more disruptive.

(3) Prof. Roni Gamzu, Israel’s new COVID czar, unveiled his “Shield of Israel” strategic plan

The Shield of Israel plan has three main arms: 1) a new contract will be established between the public and those managing the coronavirus crisis; 2) the IDF will take over the management of testing and contact tracing; 3) data will be consolidated and presented in a unified manner.

[…] With regards to “test, trace, isolate,” the methodology that experts believe is key to stopping the spread of the pandemic, Gamzu admitted that until now the Health Ministry has not done a sufficient job. As such, “the IDF will deal with this,” he said.

“The IDF’s involvement is very important because it is a system that can work quickly,” Gamzu said. […] Earlier in the day, Gamzu met with the heads of local authorities and shared more about his plan, including that testing will be increased to 60,000 people per day within the next two months and ultimately up to 100,000 by winter. He said he wants to manage cities according to their rates of infection, designating them red, orange or green.

The Health Ministry clung for dear life unto the responsibility for testing and tracing, but their practically implementation is at this point a logistical problem first and foremost. It makes sense that a logistical problem is handled best by experts in logistics — be they from the army or from industry.

According to the COVID19 data dashboard of the Ministry of Health (just updated) we now have 34,521 active COVID19 cases. Just 747 of these (2.2%) are in hospital, including 148 (0.43%) in moderate condition and 328 (0.95%) in severe condition. (I presume the 271 hospital cases with mild COVID19 are mostly people actually hospitalized for other ailments.)
Total recovered cases are at 32,722. We seem to be reaching a plateau with about 2,000 new positive cases per day, and (with wild variations due to reporting quirks) about 500 new recoveries per day (which will obviously lag by 15-30 days).

(4) On a related note, tonight starts the Jewish fast day of Tisha be-Av — when we remember the destruction of the First and Second Temples and the many other calamities that befell the Jewish people and are associated with this date. The Israel Chief Rabbinate has ruled that people who test positive for COVID19 should not fast — whether or not they feel ill — and that public prayer services (on this day we read the Book of Lamentations) should be abridged for reasons of public health.

Let me end with former Chief Rabbi of the UK, Dr. Jonathan Sacks, and his special message for Tisha be-Av in the age of corona. This is a message for all humanity, not just for Jews.

COVID19 update, July 28, 2020: Dr. Seheult retrospective on COVID19; logistics of testing; Matt Ridley’s five reasons to be optimistic

(1) In Dr. Seheult’s 100th update, he gives a retrospective, together with a brief discussion of the promising beta-interferon trial. At the end, we get a brief musical lagniappe. (He is apparently an amateur classical organist, seen here playing BWV 565 on the organ at Nantes Cathedral, which one of his ancestors helped build.)

(2) Wendover Productions is an educational channel that mostly centers on aviation, logistics, and engineering, with occasional geopolitics thrown into the mix. Here they discuss the logistics of COVID19 testing, as well as the concept of “pooled testing”.

In a nutshell, pooled testing saves resources as follows. If you need to test 100 people, it needs 100 “slots” in your automated RT-PCR machine. Now imagine you do the following: create 25 “pools” of 4 samples, create a mix for each pools of a fraction of each sample, then test these 25 mixes (requiring just 25 slots). If a mix comes back negative, all four patients in it are negative, end of story. If a mix comes back positive, you go back to the stored rest of the four samples in the mix and run those individually.
If you have a positive test rate of 8% in a population, for example, each batch would have a 28.36% chance (i.e., 100%*(1 – 0.92^4) of having at least one positive sample in the mix, or about 7 out of out 25 batches. For these you do individual testing on the remaining fraction of each sample, which requires 7*4=28 additional slots. So you can now handle 100 samples with 25+28=53 testing slots.

Clearly, as the percentage of positive tests runs up, this can become a mug’s game, while as it goes down, you could speed things up further and/or expand testing for the same capacity by creating larger pools. A group at UC Berkeley proposed using an artificial intelligence model of the population to guesstimate an infection rate, then automatically optimize pool size based on that.

(3) In the Daily Telegraph, Matt Ridley gives 5 reasons for optimism: (non-paywalled copy on his blog):

1. Vaccine trials are promising
2. (Practical) herd immunity may be more quickly reached than previously thought, owing to cross-immunity with different coronaviruses in a large swath of the population
3. Quoting: ” The one place where the virus did spread with horrible ease was in care homes and hospitals. Why was this? T-cell senescence is an issue, so old people’s immune systems are just not as good at coping with this kind of infection, and there were dreadful policy mistakes made, like stopping testing people, clearing patients out of hospitals to care homes without tests, and assuming no asymptomatic transmission. Healthcare and care home staff were not properly protected and were allowed to go from site to site. Many were infected and became carriers. [Now we know better.]”
4. “The fourth cause for cheer is therefore that now we know about asymptomatic transmission, we have more protective equipment and we have a better, if still imperfect, capacity to test, track and isolate cases, it is likely that the hospital-acquired epidemic of the spring will not be repeated.”
5. “My fifth excuse for being hopeful is that we now know better how to treat people who get seriously ill. Ventilation is not necessarily the answer, blood clotting is a real threat, making patients lie face down is helpful, dexamethasone can save lives and some antiviral drugs are showing promise.”

He also notes that due to social distancing (even short of lockdown), not only was the covid19 epidemic mitigated, but annual deaths due to seasonal influenza were significantly reduced, which is one reason overall excess mortality during the flu season was considerably less than the COVID19 death toll. Read the whole thing: Matt Ridley’s prose is lucid as always.

COVID19 update, July 27, 2020: Dr. Campbell explains the science behind vitamin D and the immune system

Just a brief post, as I’m battling a deadline at work: in this video, Dr. Campbell explains the science behind vitamin D and its role in the immune system.

This is a paper that just came out he is referring to: https://doi.org/10.3390/nu12072097

See also the previous item.

COVID19 update, July 26, 2020: Israeli large-cohort study shows vitamin D insufficiency linked to both higher suspectibility to COVID19 infection and larger risk of hospitalization

The main COVID19 news item of the day is an Israeli study that just came out (in accepted manuscript form, i.e., after peer review) in FEBS Journal (FEBS=Federation of European Biochemical Societies).

The authors are affiliated with the medical schools of Tel-Aviv and Bar-Ilan Universities, as well as with the Leumit Health Services HMO (one of the four licensed HMOs in Israel — which has an HMO insurance mandate). They went through the Leumit patient database and looked at patients tested for COVID who had at least one recent blood test for vitamin D levels. Other health data were collected in order to correct for confounding factors. After screening, 782 COVID-19 positive and 7,025 COVID-19 negative patients remained. Note that the time window for COVID19 testing was February 1 to April 30, 2020 — i.e., before our sunny season.

https://doi.org/10.1111/febs.15495

From the abstract:

[…]“Suboptimal” or “low” plasma 25(OH)D level was defined as plasma 25-hydroxyvitamin D, or 25(OH)D, concentration below the level of 30 ng/mL.
Results: Of 7,807 individuals, 782 (10.1%) were COVID-19-positive, and 7,025 (89.9%) COVID-19-negative. […] Univariate analysis demonstrated an association between low plasma 25(OH)D level and increased likelihood of COVID-19 infection [crude odds ratio (OR) of 1.58 (95% CI 1.24-2.01, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [crude OR of 2.09 (95% CI 1.01- 4.30, p<0.05)]. In multivariate analyses that controlled for demographic variables, and psychiatric and somatic disorders, [these conclusions] were preserved. […]

Dr. John Campbell has been going hammer and tongs at vitamin D insufficiency on his YouTube channel, and an association has been shown by study after study. This is just the latest, and on a relatively large cohort.

I do know that dietitians in at least one HMO here have recently been told to routinely prescribe vitamin D supplements across the population. Presumably deficiency is less of an issue now in the summer than in winter.

At any rate: vitamin D deficiency is (for most people) cheap and easy to correct with supplements.

ADDENDUM: according to De Standaard (in Dutch) Belgium is seeing its highest new infection numbers in 3 months. A 3-year old toddler is among recent victims — underscoring that, while the risk of fatal complications is way lower in young people, it is not zero. The paper also reports on the aftermath of the disease in college-age young people: about 6,500 twenty-somethings got the disease in Belgium. Only few of those ever need to go to the hospital, but symptoms may linger for months afterward. The college students the paper interviews, months after surviving COVID19 bouts, still have symptoms such as fatigue, shortness of breath, chest pain,… A recent local medical survey found the following as most reported sequelae three months after infection: fatigue (86%), shortness of breath (53%), headache (41%), muscle pain (40%) and a sensation of pressure on the chest (36%).

Brief COVID19 update, July 25, 2020: mostly video edition

A few quick updates, mostly video:

(1) A somewhat UK-centric world update from Dr. John Campbell

(2) The Economist on why the stock market is doing pretty well despite the corona crisis. Jeb Kinnison mentioned the economic law that whenever new money is issued, those sitting closest to the source of new money enjoy an economic advantage as they are able to spend it before everybody becomes aware of its loss of value — needless to say, not mentioned here.

(3) Swedish epidemiology chief Anders Tegnell says, “judge me in a year”.

(4) Jeff Duntemann alerted me to an e-book by Dr. Zev Zelenko and others. A community doctor in the Satmar Chasidic community, he started applying a treatment regime of hydroxychloroquine, zinc supplements, and the antibiotic azithromycin quite early (around the same time as Dr. Didier Raoult, director of the Marseille hospital for infectious diseases, applied his regime).

HOCQ came out of the drug repurposing effort — the whole idea being that while developing a new drug and getting FDA approval takes time, this can be shortcut if an old drug can do new tricks. (In fact, some of the best-known drugs came about exactly like this: Ritalin, Viagra, Antabus,…) There are two factors clouding the issue here:

(a) unlike the pretty clear, transparent mechanisms by which drugs like remdesivir, dexamethasone, and beta-interferon work, the mechanism for HOCQ is murkier even if we have a few conjectures. (The cardiac risk being spoken of is for azithromycin, not for hydroxychloroquine itself which at lower doses is routinely used in lupus patients as an immunomodulator.)

(b) TDS (Trump derangement syndrome): to me, the concept of wanting a drug to fail simply because a politician one despises endorsed it reminds me of middle school except that people’s lives are at stake. It is the sort of behavior where the Brahmandarin “smart set” unintentionally reveals more about itself than about pharmacology.

At this stage, I’m more bullish on beta-interferon and dexamethasone, but I’ll take whatever works, be it one drug or a “cocktail” regime. If we can make it so that we can reliably arrest the progression of the disease from upper respiratory tract to dangerous pneumonia with ARDS, then we can treat COVID19 like a nuisance rather than a dangerous epidemic.

(5) Via Instapundit: This chart of US State’s fatalities per capita (full version here) is perhaps most notable for which states do not show up in the top bracket:

(6) Meanwhile in Israel, Prof. Gabi Barabash declined the offered position of “Coronavirus czar” — instead Dr. Roni Gamzu (Barabash’s successor as the director of Ichilov Hospital, and like him a former director-general of the Health Ministry) will take the position.

COVID19 update, July 22, 2020: beta-interferon a breakthrough treatment?; As many as 50-60% of people may have pre-existing T-cell immunity; Flare-up in Belgium

(1) This could be huge: as Dr. John Campbell explains in the following video

a team based at U. of Southampton carried out a clinical trial with beta-interferon. Dr. Campbell explains how this is part of the natural immune system of the body, and how COVID19 apparently interferes with its production, making cells not only more vulnerable to spreading COVID19 infection but indeed making them more susceptible to opportunistic secondary infection by, say, influenza viruses. (If you think COVID19 alone is bad news, imagine it together with a bad flu, and if you want a real nightmare scenario, throw a bacterial pneumonia over the top.)

Here is a press release. The TL;DR points:

• this was a small study (100+) with a placebo group. If anything, the sample was skewed against the drug, as the treatment group had more people with risky pre-existing conditions
• half the patients were treated with beta-interferon through inhalation, the other half with a placebo
• the odds of developing severe disease were reduced by four-fifths in the treatment group compared to the control group
• in the placebo group, six people died. None died in the treatment group
• on average, patients in the treatment group were discharged after six days, versus nine days for the control/placebo group
• subjectively, the treatment group reported much less difficulty breathing than the placebo group

It should be pointed out that beta-interferon has been in clinical use as a drug for decades, notably (under the brand names Rebif, Avenex,…) for the autoimmune disease, multiple sclerosis.

The BBC:

Interferon beta is part of the body’s first line of defence against viruses, warning it to expect a viral attack. The coronavirus seems to suppress its production as part of its strategy to evade our immune systems. The new drug is a special formulation of interferon beta delivered directly to the airways via a nebuliser which makes the protein into an aerosol. The idea is that a direct dose of the protein in the lungs will trigger a stronger anti-viral response, even in patients whose immune systems are already weak.

This type of drug is impossible to administer orally (it would just be digested): in multiple sclerosis it is injected (Avonex typically intramuscular, Rebif typically subcutaneously — with a little practice, self-administered just like insulin).

(2) As many as 50-60% of people could have T-cell immunity for COVID-19 from prior exposure to different coronaviruses, reports the BBC.

[W]hile the world has been preoccupied with antibodies, researchers have started to realise that there might be another form of immunity – one which, in some cases, has been lurking undetected in the body for years. An enigmatic type of white blood cell is gaining prominence. And though it hasn’t previously featured heavily in the public consciousness, it may well prove to be crucial in our fight against Covid-19. This could be the T cell’s big moment.
T cells are a kind of immune cell, whose main purpose is to identify and kill invading pathogens or infected cells. It does this using proteins on its surface, which can bind to proteins on the surface of these imposters. Each T cell is highly specific – there are trillions of possible versions of these surface proteins, which can each recognise a different target. Because T cells can hang around in the blood for years after an infection, they also contribute to the immune system’s “long-term memory” and allow it to mount a faster and more effective response when it’s exposed to an old foe.  

Several studies have shown that people infected with Covid-19 tend to have T cells that can target the virus, regardless of whether they have experienced symptoms. So far, so normal. But scientists have also recently discovered that some people can test negative for antibodies against Covid-19 and positive for T cells that can identify the virus. This has led to suspicions that some level of immunity against the disease might be twice as common as was previously thought.

Most bizarrely of all, when researchers tested blood samples taken years before the pandemic started, they found T cells which were specifically tailored to detect proteins on the surface of Covid-19. This suggests that some people already had a pre-existing degree of resistance against the virus before it ever infected a human. And it appears to be surprisingly prevalent: 40-60% of unexposed individuals had these cells.

Read the whole thing.

(3) After a long gap, Israel finally has a “coronavirus czar”: Prof. Gabriel “Gabi” Barbash, the recently retired medical director of Sourasky/Ichilov Medical Center in central Tel-Aviv. (This is one of the “big 4” research and teaching hospitals in Israel, together with Tel HaShomer in the Tel-Aviv borough of Ramat Gan, Hadassah in Jerusalem, and Rambam (=Maimonides) in Haifa.) He also previously (1996-9) served a stint as director-general of the Health Ministry. We wish Gabi well in his daunting task.

New infections continue to be high here (just over 2,000 yesterday) but daily recoveries are ramping up too, reaching 589 yesterday. In fact, on worldometers, the surge in recoveries seems to lag that in new infections by about 4 weeks.

In related news, following WHO recommendations, Israel has shortened the quarantine period for COVID19 from 14 to 10 days.

(4) Belgium is the latest country to see a major flare-up: “all traffic lights show red”, headlines De Standaard (in Dutch). Further back-to-normal measures there are on hold for now.

Japan and the Wuhan Virus

Japan is one of the countries that has been least affected by the Wuflu. In terms of places where I trust the statistics, it’s done extremely well. …

Japan and the Wuhan Virus

Wuhan Virus, What We Know Today

We’re some 6 months into the Wuflu pandemic and science and medical research has taught us a lot about the virus and the disease it causes, but …

Wuhan Virus, What We Know Today

July 20-21 book promotion: Operation Flash, Episodes 1-3 all free on Amazon

To mark the anniversary of Operation Valkyrie [July 20, 1944] the novella series Operation Flash, Episodes 1-3 will be free on Kindle on Monday, July 20 and Tuesday, July 21.

This is a “hard alternate history” series that explores a timeline in which an actual suicide bombing plot on March 21, 1943 did succeed. The conspirators soon discover that killing Hitler and most of the Nazi top was actually the easy part…

Selected reviewer comments:

• “As real as being there in person”
• “Absorbing alt-history story”
• “Immediately took me to the time and place. It was refreshing not to be distracted by anachronism of thought and culture.”
• “well written, brilliantly researched and very believable.”

The entire series is on Amazon at this link: https://www.Amazon.com/gp/product/B07WVNRMSV

Episode 3: Spring Awakening

Episode 2: Hinges Of Fate

Episode 1: Knight’s Gambit Accepted

COVID19 update, July 18, 2020: six severity levels based on symptoms; about 90% of infections in young children are asymptomatic; ivermectin results in humans promising

(1) Dr. John Campbell on the current situation in the UK

A few points for the impatient:

• antibody testing indicates that the official case numbers are an underestimate by about a factor of ten
• however, based on data from Sweden where they were able to test for memory T-cells (a much harder test), about twice as many people have immunity as the simpler antibody test indicates
• That corresponds, in aggregrate, to a Dunkelziffer (hidden infection rate) of about 20:1
• about 6% of school children in the UK have antibodies. Significantly, only 1 on 10 of them reported ever having had any symptoms. Or, to put it differently, 90% of cases in that age bracket are asymptomatic. I have been suspecting for a while that not just severity of the disease is age-dependent, but also the rate of symptomatic infection.

(2) An article in the Daily Telegraph comments on a recent study analyzing responses to an AI-driven diagnostic tool. As a control, the trained AI was applied to a different set of patients and validated against more conventional diagnoses.

The trouble with machine learning is that, while it’s great at “imitation games”, it’s not so great at answering Eugene Wigner’s plea: ‘I’m glad that the computer understands it — now I want to understand it too’. That being said, six clusters of cases emerged with six distinct sets of symptoms. Arranged in ascending order of severity:

1. (Flu-like with no fever): Headache, loss of smell, muscle pains, cough, sore throat, chest pain, no fever. [1.5% require respiratory support of any kind]

2. (Flu-like with fever): Headache, loss of smell, cough, sore throat, hoarseness, fever, loss of appetite.[4.4% require respiratory support of any kind]

3. (Gastrointestinal): Headache, loss of smell, loss of appetite, diarrhoea, sore throat, chest pain, no cough.[3.3% require respiratory support of any kind]

4. (Severe level one, fatigue): Headache, loss of smell, cough, fever, hoarseness, chest pain, fatigue.[8.6% require respiratory support of any kind]

5. (Severe level two, confusion): Headache, loss of smell, loss of appetite, cough, fever, hoarseness, sore throat, chest pain, fatigue, confusion, muscle pain.[9.9% require respiratory support of any kind]

6. (Severe level three, abdominal and respiratory): Headache, loss of smell, loss of appetite, cough, fever, hoarseness, sore throat, chest pain, fatigue, confusion, muscle pain, shortness of breath, diarrhoea, abdominal pain. [19.9% require respiratory support of any kind]

(3) Aerosol transmission: this group from Amsterdam https://www.medrxiv.org/content/10.1101/2020.07.16.20155572v1.full.pdf

experimentally studied the spread of droplets and aerosols from healthy subjects breathing, speaking, and coughing. They conclude that aerosol transmission will be an inefficient route.

(4) Dr. Seheult on some new results that seem to show ivermectin, earlier hown to inhibit COVID-19 in the test tube, is actually fairly potent in human patients https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3636557

Dr. Seheult discusses possible mechanisms, as well as the role of von Willebrand factor in blood clotting

COVID19 update, July 17, 2020: second waves in Japan and Israel with lower mortality

“Masgramondou” drew my attention to the Japan COVID19 tracker site: https://covid19japan.com

There is apparently a second wave going on there. Reportedly, it is driven mostly by super-spreader events at theaters. Unlike in the 1st wave, it seems an active track-and-trace effort on the South Korean and Taiwanese model is being implemented.

Now from where do we start counting the 2nd wave? A somewhat arbitrary method is to look for the minimum in the active cases on worldometers (around June 24), and count from there.
In the time frame June 24–July 16, total confirmed cases went from 18,024 to 22,890, an increase of 4,866. In the same interval, cumulative deaths went from 963 to… 985, an increase of just 22. That implies an apparent case fatality rate (CFR) ≥0.49%. (Equal or greater, since deaths typically lag infections by up to 3 weeks.) Still, that figure is nothing like what was seen in the first wave: 963 dead in 18024 works out to 5.3%.

Reasons? DId the virus get weaker? Did the weakest already either die off or survive the infection? Is testing and tracking so much better this time around, so many more asymptomatic and mild cases enter the denominator and drag down the CFR? Or do doctors have more successful strategies to treat the disease? My money is on “all of the above”.

Now to Israel, where I live. Here the minimum in active cases, according to worldometers, falls around May 28, when we had 284 dead and a total of 16,872 confirmed infections. Our total confirmed infections have meanwhile risen by nearly twice that number — 29,187. Yet our total dead over the same period have gone up by “just” 100. Still 100 too many, to be sure, and caveat about deaths lagging cases, but… at ≥0.34%, that’s about one-fifth the apparent CFR of 1.68% in the first wave!!

Israel has a very detailed data dashboard (Hebrew only) that even displays occupancy rates of COVID wards in hospitals, as well as a breakdown by light, moderate, and severe case counts, or even the number of patients on respirators. At present, we have 120 moderate and 213 severe cases: note that these figures are just 0.41% and 0.73%, respectively, of all confirmed diagnoses!
Aside from the possible causes pointed out above for Japan, Israel has a “young” population (median age 31 according to the CIA World Factbook, compared to 48 for Japan). But even so, the age distribution of patients according to the dashboard shows an overrepresentation in the age groups 10-19 and especially 20-29.

There were no mass demonstrations here, but the economy opened pretty rapidly as soon as the first wave seemed behind us, and young people were clearly just tired of being cooped up. So they went out and partied: the trouble here isn’t so much hanging out together on the beach (open-air activities are probably fairly safe) but going to crowded clubs and bars, and especially the lack of prudent physical distance.

Our authorities look upon masks as the be-all and end-all — but methinks refraining from hugging, kissing, etc. between casual friends would be a good deal more effective. (That aside, the concept of personal space is almost foreign to Israelis. This surely does not help in such a crowded country.) As a colleague put it: “would be good if Israelis would become a bit more English for the duration”.

Our news media cry out every day about “new records” in new cases (1,871 yesterday, or more than twice the peak of the first wave), while everybody overlooks that daily recoveries are likewise increasing (reaching 381 yesterday and on an upward trajectory).

The health authorities, however, anxiously see occupancy of COVID19 wards climb (at least the seasonal flu and pneumonia waves are not taking up beds right now) and reach full capacity at Tel HaShomer (“Sheiba”), Shaaei Tzedek, and Assaf HaRofeh (“Shamir”) hospitals, and indeed exceed rated capacity at Hadassah Ein Kerem. For this reason, there is a push for a a brief but hard second lockdown on their part; pretty much nobody else is keen on one, as our economy was so hard-hit by the first lockdown. Netanyahu’s coalition partners, particularly Alternate Prime Minister Benny Gantz, are particularly adamant aboyt this

So the government came up with a “Belgian compromise” (i.e., one that makes everybody unhappy) where restaurants have to switch to delivery and takeaway, gatherings of more than 10 people indoors or 20 people outdoors are banned, and restaurants and malls are closed over the “long Sabbath” (Friday 5pm until Sunday 5am), but the weekday economy continues to operate. Also, the mask mandate is now being enforced, unlike (generally) in the past.
Various accusations fly each and every way, connected to political infighting and turf wars. Also, I suspect that a number of decision makers have reached the conclusion the first lockdowns around the world were an overreaction, and may now be (consciously or unconsciously) leaning toward a laissez-faire approach. The end result is, however, that the coherence of our coronafighting effort in the first wave seems to be lacking this time around. We may end up with a form of “unintentional herd immunity strategy” on the Swedish model, with efforts focused mostly on protecting the most vulnerable and improving treatment of severe cases. With luck, we might enter the winter with much of the population either immune from past infection, or having pre-existing partial or complete immunity.

One of the more creative ideas I heard bandied around was to try and mitigate until before the High Holidays, and then carry out a full lockdown over Rosh HaShanah and Yom Kippur, during a period when our economy basically shuts down anyway.

Gloomy compared to the euphoria of mid-May, when other countries looked to Israel’s first-wave success? Not all gloom: the sharp reduction in mortality (which echoes other countries, like the UK and Italy) is definitely the silver lining.

Meanwhile, Mrs. Arbel sent me this (isolated, to be sure) report of a medical professional being reinfected after getting ill and apparently recovery.

Have a great and healthy weekend, and shabbat shalom

UPDATE: University of Akron cutting 20% of faculty, including tenured faculty, citing COVID-19. Interestingly, Inside Higher Ed reports:

Regarding COVID-19 in particular, many institutions are considering faculty cuts. But Akron is a particular flash point because it is cutting so deep, and because of intense and very public faculty opposition to its plan. That opposition includes the faculty union’s contention that the administration is privileging athletics over academics, to the detriment of students.

“For years, the university has disinvested in academics while simultaneously losing millions on its athletics programs,” Akron’s chapter of the American Association of University Professors wrote in a position paper about proposed cuts earlier this month. “In the spirit of shared sacrifice, we believe that it’s time to move to a responsible and sustainable model of funding for athletics.”

While the vast majority of university revenue comes from academics in the form of student tuition and fees, the union wrote, its athletic programs are another story. According to the AAUP chapter’s accounting, Akron has been losing an average of $21.5 million per year on athletic programs for the last 10 years, topping $215 million in lost revenue during that time. Among other options, the AAUP advocates leaving Division I of the National Collegiate Athletic Association.

COVID19 update, July 16, 2020: vitamin D redux; airborne transmission; impact of work-from-home on London; new revelations on T-cell response and persistent immunity

Today, a bit of a bumper crop of COVID19 news.

(1a) Dr. Seheult about, once again, vitamin D. 

At least in Israel, HMOs have woken up to the deleterious effects of vitamin D deficiency: when I checked in with my dietician (over the phone) for a routine follow-up, I told her about the vitamin D and Zn supplements I’d been taking since the beginning go the outbreak, and she mentioned that her HMO (Maccabi) issued guidelines to recommend vitamin D supplements to the entire population. 

Another aspect of Israel’s COVID19 response was revealed to me when a friend (a literary translator) developed flu-like symptoms and tested positive. (She is self-isolating at home with her husband.) The next day, she received a parcel from her HMO with a fingertip pO2 meter (i.e., a blood oxygen saturation meter), accompanied with instructions to check several times a day, and to call immediately if her pO2 dropped significantly. This acts as an inexpensive but reliable early warning system for deteriorating condition.

(1b) Dr. Mike Hansen discusses airborne transmission and masks

Relatedly, a study about the effect of universal masking policies at Brigham and Women’s Hospital was just published in JAMA . In a word, the masks are valuable in a healthcare setting. This does not necessarily mean the study militates in favor of universal mask mandates among the general population. (In fact, for aerosol transmission, surgical masks are likely not very useful.) 

(2) Is “the 30-year old who attended a COVID party and died”  a ‘fake but accurate’ story?

(H/t: Jeff Duntemann). It seems that the NYTimes has dropped all pretense of reporting the news and is now only reporting “truth” (Pravda, in the original Russian). Bari Weiss’s resignation letter speaks volumes.

(3) One man’s meat is another man’s poison: Norwegian undertakers want state aid as they have too little work

And an essay in the Daily Telegraph uses the hyperbolic term, “extinction-level event”, for what the shift from commuting to home-working is doing to central London. I would not blame this on COVID-19 though: that shift was waiting to happen (especially in one of the most expensive real estate markets in the world) and COVID merely the trigger.

(4) Some years after a sting operation revealed the operation of scientific paper ghostwriting operations in China, new revelations  (See also here.)

(5) https://www.telegraph.co.uk/news/2020/07/13/german-study-finds-no-evidence-coronavirus-spreads-schools/

But Israeli expert Ehud Kliner is blaming the second wave in the country on… reopening the schools.

(6) Media should do a major mea culpa on hydroxychloroquine, as a new study adds fuel to the fire.

(7) Daily Telegraph exclusive: Good news about the Oxford/AstraZeneca vaccine trial.

(8) Last but definitely not least for today, Derek Lowe discusses new papers on antibodies, T-cell response, and COVID-19.

Turning to patients who had caught SARS back in 2003 and recovered, it is already known (and worried about) that their antibody responses faded within two or three years. But this paper shows that these patients still have (17 years later!) a robust T-cell response to the original SARS coronavirus’s N protein, which extends an earlier report of such responses going out to 11 years. This new work finds that these cross-react with the new SARS CoV-2 N protein as well. This makes one think, as many have been wondering, that T-cell driven immunity is perhaps the way to reconcile the apparent paradox between (1) antibody responses that seem to be dropping week by week in convalescent patients but (2) few (if any) reliable reports of actual re-infection. That would be good news indeed.

And turning to patients who have never been exposed to either SARS or the latest SARS CoV-2, this new work confirms that there are people who nonetheless have T cells that are reactive to protein antigens from the new virus. As in the earlier paper, these cells have a different pattern of reactivity compared to people who have recovered from the current pandemic (which also serves to confirm that they truly have not been infected this time around). Recognition of the nsp7 and nsp13 proteins is prominent, as well as the N protein. And when they looked at that nsp7 response, it turns out that the T cells are recognizing particular protein regions that have low homology to those found in the “common cold” coronaviruses – but do have very high homology to various animal coronaviruses.

Very interesting indeed! That would argue that there has been past zoonotic coronavirus transmission in humans, unknown viruses that apparently did not lead to serious disease, which have provided some people with a level of T-cell based protection to the current pandemic. This could potentially help to resolve another gap in our knowledge, as mentioned in that recent post: when antibody surveys come back saying that (say) 95% of a given population does not appear to have been exposed to the current virus, does that mean that all 95% of them are vulnerable – or not? I’ll reiterate the point of that post here: antibody profiling (while very important) is not the whole story, and we need to know what we’re missing.

COVID19 update, July 15, 2020: some observations on per-capita mortality ranking of OECD countries

Just how badly are the USA and Israel really doing, when adjusted for population?
From the news media in both countries, you’d say “terribly”. But mortality figures per capita tell a rather different story.
First, I went to worldometers and extracted a table of mortalities per million inhabitants. Then I whittled the list down to the 37 OECD member states. The resulting table is given below as an image. [The “ranking” refers to the original sorted list]

A few remarks are in order.

• the #1 and #3 fatality rates worldwide are actually for the microstates of San Marino and Andorra, respectively. Beware statistics of small numbers though.
• As I’ve commented before, Belgium’s chart-topping fatality rate almost certainly includes lots of people who died of causes other than COVID19, but either tested positive for COVID19 or were suspected to have been exposed.
• Even the unadjusted US figure is still only about half the Belgian one, and places the country #7 in the OECD and #9 worldwide.
• However, these numbers are badly skewed by the appalling mortality rate in greater New York City. If we drill down to US states and take NY and NJ out of the equation, mortality drops to 300 per million — which would make the US #16 worldwide behind the Dutch Antilles island of St. Maarten, and ahead of Ecuador. In the OECD it would be above Mexico.
• Germany, which is regarded as a “gold standard” in Europe for its (objective speaking) highly competent handling of the COVID crisis, still has a mortality above the world average.
• Israel, despite the hue and cry about the public health authorities and the government being rudderless now (and this is not without grounds!) still only comes at 27th place out of 37 in the OECD, and still has 2.5x lower per capita mortality than Germany! (Not to mention 1/10th of the USA and 1/20th of Belgium.) [EDIT: only four US states have lower per-capita mortality rates than Israel: sun-drenched, outdoorsy Hawaii and the thinly populated trio of Wyoming, Montana, and Alaska.]

When news media take numbers out of context, it is good to go to the source figures for some perspective.

COVID19 update, July 14, 2020: Israel’s second wave exceeds first; possible drug breakthrough; aerosol transmission; link dump

(1) Israel’s second wave seems to be exceeding its first wave in documented infections, but so far (thank G-d) not in mortality. Yesterday’s number of newly diagnosed cases was an all-time high. Still, with 22,324 active documented cases as of the time of writing, we have 114 moderate cases (0.5%) and 183 severe cases (0.8%), with just 56 patients on respirators. Testing capacity did increase: we now routinely reach up to 30,000 tests per day, in a country of 8+ million people. 

The Health Ministry gives the impression of being at the same time overwhelmed and unwilling to let any others help out. Prof. Siegal Sadetski resigned some days ago with a blistering resignation letter; today the head of the emergency corona commission during the first wave,Prof. Eli Waxman (a well-known physicist from the Weizmann Institute), gave a pretty outspoken assessment.

Own-goals like over 12,000 people being mistakenly told to go into quarantine as tracking apps on their phones supposedly had identified them as being exposed do not exactly inspire great confidence. (To be fair, the domestic security service did not want this mass tracking job, but it was dumped upon them.)

Nobody (in their right mind) wants another lockdown as the economic consequences would be terrible, but the lack of self-discipline on the part of especially the younger public may push the country into a corner where it has no other option. We’re not even talking about severe social distance here, just refraining from hugging, kissing, and back-slapping with casual buddies. 

(2) This is big if it pans out: Hebrew U. Scientist and his Mount Sinai collaborator (that sounds odd) claim to have found that already-approved drug Fenofibrate (Tricor), a hypolipidemic used in the treatment of metabolic disorders, impedes SARS-CoV-2  infestation of the lungs to such a degree that it will reduce  COVID-19 to an unpleasant nuisance rather than potentially life-threatening.

The preprint of the paper is at

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3650499

(3) Link roundup:

* Jeff Duntemann brought this older paper to my attention:

https://doi.org/10.1098/rsif.2009.0302.focus

It deals with aerosol transmission of influenza viruses, but should be directly relevant to COVID19

* When discussing covid19 morbidity and mortality in younger people, the following numbers for other causes of death(e,gf, traffic accidents) may serve as a sanity check. 

* Chemical and Engineering News wonders if Europe could develop its own electric car battery industry and wean itself off dependence on Chinese suppliers.

* multiple sources report that in a major reversal by Boris Johnson, the UK bars Huawei from supplying the new 5G network  

*  (Via Instapundit.) And just what  testing numbers from Florida can you trust? Why having multiple labs turn in 100% positive test results did not raise red flags is beyond me.

* Also via Instapundit: Meanwhile in India, a new drug was approved:

INDIA: Biocon’s Itolizumab approved for COVID-19 treatment: All you need to know. “The company has received approval from the Drugs Controller General of India (DCGI) to market Itolizumab injection 25mg/5mL solution for emergency use in India for the treatment of cytokine release syndrome in moderate to severe acute respiratory distress syndrome (ARDS) due to COVID-19. Biocon says Itolizumab is the first novel biologic therapy to be approved anywhere in the world for treating patients with such complications.”

COVID19 update, July 12, 2020: Sweden redux and immunity; inhaled steroids; BCG vaccine redux

UnHerd interviews a Swedish medical researcher and practicing physician about what things are like there now. It seems the epidemic is winding down there now. Let me start up with Worldometers:

And a Swedish journalist fisks the NYT’s article about the Swedish response, which isn’t isn\t quite the horror show the NYT is making it out to be. Also, it “didn\’t do nothing” — it just relied more on persuasion and voluntary recommendations rather than mandates. (Good luck with THAT when dealing with Belgians, Israelis, or New Yorkers ;))
Maybe Sweden spared itself a 2nd wave by not locking down so tight in the 1st wave? 

(2) Dr. Seheult on inhaled steroids:

(3) I’ve mentioned earlier speculation that past TB vaccination with the BCG (bacille Calmette-Guérin) vaccine may impart a degree of protection against COVID19. Now a story affirming this got published in the prestigious Proceedings of the National Academy of Sciences: https://doi.org/10.1073/pnas.2008410117

The COVID-19 pandemic is one of the most devastating in recent history. The bacillus Calmette−Guérin (BCG) vaccine against tuberculosis also confers broad protection against other infectious diseases, and it has been proposed that it could reduce the severity of COVID-19. This epidemiological study assessed the global linkage between BCG vaccination and COVID-19 mortality. Signals of BCG vaccination effect on COVID-19 mortality are influenced by social, economic, and demographic differences between countries. After mitigating multiple confounding factors, several significant associations between BCG vaccination and reduced COVID-19 deaths were observed. This study highlights the need for mechanistic studies behind the effect of BCG vaccination on COVID-19, and for clinical evaluation of the effectiveness of BCG vaccination to protect from severe COVID-19.

Finally, “Five Foot of Lutheran Fury” Mollie Ziegler Hemingway, while acknowledging the seriousness of the epidemic, tells her fellow Americans to react rationally rather than the “h” word she uses.

COVID19 update, July 10, 2020: aerosol transmission; empirical studies on choir rehearsals and office buildings; some neighborhoods of NYC at herd immunity?; deaths in British care homes linked to contract labor

(1) Dr. John Campbell on airborne aerosol transmission

The article he refers to is this one:

https://doi.org/10.1093/cid/ciaa939

In a nutshell: while a 1-2 meter “social distance” is useful against larger droplets (which fall to the earth), this does not apply to aerosols (made up of droplets of 5 micron or smaller) which can spread dozens of meters through the air and keep hanging for quite a whole. Your typical cloth or surgical mask will not be very helpful against aerosols either. (A true N95 mask, that conforms to the NIOSH N95 standard, is supposed to block 95% or more of particulate matter at  0.3 micron size.)

So what can you do? In a word: refresh the air. Outside activities are safest from an aerosol perspective (especially if there is at least some breeze), and small or tightly packed enclosed spaces with no air refreshment from outside are the worst. (I used to think planes would be the very worst, but Air Canada, in a recent mailing to me, claims that not only do they turn over all cabin air at a rate of one full refresh every three minutes, but they filter the air through HEPA filters.)

(2) Aerosol transmission: how dangerous is singing, really? A reporter from Die Welt (herself a member of the Berlin philharmonic chorus) discusses (in German)  a study by engineers from the Technical University of Berlin. 

The people involved are professionally mostly interested in the design of ventilation systems for large office buildings and residential complexes. As the whole issue of aerosol transmission of COVID-19 started coming to the fore, and reports of super-spreader events at choir rehearsals (notably this well-studied one in Washington state) and religious services with singing kept coming up, they asked themselves the question: can we empirically test and quantify this? Do singers spread more aerosol droplets than people speaking or going about their daily activities?

So they recruited eight volunteers from the RIAS Chamber Choir in Berlin and had them, inside a “cleanroom” breathe,  then speak, then sing at a range of volumes into funnels connected to a special apparatus in which a laser particle counter measures and counts aerosol droplets. A preliminary report (in German) is available  here on the university’s preprint server. The English abstract (some “Gerglish” corrections for clarity in square parentheses):

n this study, emission rates of aerosols emitted during singing are presented for professional singers. The results, measured with a laser particle counter, are compared with published data for breathing and speaking. In the investigated cohort of eight volunteers, the particle source strengths during singing are between 753.4 and 6093.14 [articles per second]. The [increase factor in emission] rates [when] singing [compared to] speaking [is] between 3.98 and 99.54. The present study contributes to a more precise assessment of a possible spread of SARS-CoV-2-viruses during singing. It should support the efforts to improve the risk management, especially for choir singing.

From Figure 4 of the whole report, we see also that the aerosol particle concentration (particles of 5 micron and smaller) was statistically well correlated (R**2 = 0.824) with the volume in decibels: Log10 (concentration) = 0.07 (volume in dB) – 2.41.

The researchers then carried out a second study (preliminary report here) in which they tried to see under which circumstances choir rehearsals could be made no more dangerous (from the point of view of aerosol exposure) than an ordinary office building. In their simulation, they achieved this for a given rehearsal room (the auditorium of a local school) by spacing the participants at 2m distance and, instead of having them sing for 2h at a stretch, sing for half an hour at a time with 15=-minute breaks during which all windows of the hall were opened wide.

Perhaps the most counterintuitive conclusion was that the audience and orchestral musicians at classical music performances in large halls, like those of the Berlin Philharmonic and its Dresden counterpart, are surprisingly safe, thanks to the very large and high-ceilinged halls and the efficient forced-ventilation system. (This was in place for very different reasons: reduce accumulation of CO2.)

Graph address: https://img.welt.de/img/gesundheit/mobile211378363/5007931917-coriginal-w780/DWO-WS-Corona-Chor-js.jpg

This graphs shows the concentration of potentially infectious aerosol particles per square meter in different spaces. Lowest are the large, high-ceilinged  concert halls of the Dresden and Berlin philharmonics; above that is an office with forced ventilation, about the same as a choir rehearsal room with a single infected person; higher (in blue) is an office with just window air (presumably different if you sit by the window); and at the top is a choir rehearsal room with three infected participants. The descending segment in the middle represents the effect of a 15-minute “airing out” after 30 minutes. 

(3) The Daily Telegraph reports that some neighborhoods of New York have shown up unprecedentedly high percentages of positive antibody tests — reaching 1st-order herd immunity levels. 

Areas of New York have recorded a nearly 70 per cent rate of immunity to Covid-19, in what scientists have described as “stunning” findings that suggest they could be protected from any second wave.

Some 68 per cent of people who took antibody tests at a clinic in the Corona [you can’t make this up! — Ed.] neighbourhood of Queens received positive results, while at another clinic in Jackson Heights, 56 per cent tested positive. 

The results, shared by healthcare company CityMD with the New York Times, appear to show a higher antibody rate than anywhere in the world, based on publicly released data.

The next closest is the Italian province of Bergamo, which recorded 57 per cent, followed by Alpine ski resort Ischgl, the site of Austria’s biggest coronavirus outbreak, which reported 47 per cent.

[…]

Wealthier areas recorded much lower rates, according to CityMD data. For example, at a clinic in Cobble Hill, a mostly white and wealthy neighbourhood in Brooklyn, only 13 per cent of people tested positive for antibodies.

The results suggest higher-income neighbourhoods may bear the brunt of any second wave to hit the city.

CityMD administered about 314,000 antibody tests in New York City, as of June 26. Citywide, 26 per cent of the tests came back positive.

Tangentially related, Dr. Seheult here discusses immunity testing and survey data for Spain

The paper is here: https://doi.org/10.1016/S0140-6736(20)31483-5 They retained a sample of over 61,000 (the largest of its kind so far), and used two different antibody tests on each. For Spain as a whole, the seroprevalence is only 5%, but larger towns (and especially the Madrid area) have higher figures, as do health care and nursing home workers, and — interestingly — the top 5% earners (presumably because many such people travel a lot for work). At least one-third of people who has antibodies had never had any symptoms. 

(4) Also in the Telegraph, the story of deaths in British care homes seems more complicated than meets the eye.

It has been the same, awful story everywhere. Sweden didn’t lock down and has still had fewer deaths per capita than Britain (while taking a far smaller economic hit). But a failure to protect care homes led to most of Sweden’s Covid deaths. The figures here are quite striking: care homes look after three per cent of Britain’s elderly population but accounted for 41 per cent of our Covid deaths. Similar ratios can be found in Spain, France, Denmark, Israel and Portugal.

As a result, most of Europe is now asking what went wrong in care homes – and moving to a similar conclusion. It took ages to realise how many people are barely affected by Covid, carrying (and spreading) the virus without knowing it. Asking people to isolate if they had symptoms didn’t offer much protection. The more people coming in and out of the care homes, the greater the risk of infection. If those care homes don’t offer sick pay, the risk is greater.

Hong Kong banned care home visits pretty early on: it had learned from Sars. But British care homes were taking visitors for weeks after lockdown and, even after that stopped, agency workers drifted in and out, some working in multiple homes. The Government (belatedly) advised against this “where possible”. But for most homes it is not possible: they have no staff backup. Yet again, we see the problem in the British care home industry: a refusal to pay decent wages, a dependence on casual staff and a reliance on agencies that can provide low-cost workers.

Care homes that did things differently saw very different results. In France, a home near Lyon put its staff and residents into complete isolation for seven weeks, taking no one from outside. They had no Covid deaths. Valerie Martin, its director, said she went to such lengths because “my residents still have so much to live for”. She also had carers paid enough that they didn’t need a second job and were willing to be quarantined.

It has been a very different story here. An Isle of Skye care home found that 30 of its 36 residents ended up with the virus, six of whom died. It turned out to be shipping in workers, including one from Kent. [That’s literally the other end of the UK — Ed.] A study published last week tried to explain the huge differences in how homes in England were affected. Residents looked after by agency workers were 58 per cent more likely to contract Covid. Those working in multiple care homes were more than twice as likely to carry the virus.

It might be shocking. But it’s not really surprising – given that this is the same problem we saw during the spread of superbugs like MRSA. Those lessons weren’t learned. Care homes argue, still, that their business model depends on being able to pay people less than supermarkets do. Their complaint about Brexit, even now, is that it makes it harder for them to import cheap labour and keep wages down. Their bigger concern should be what the Covid crisis has shown about their ability to protect those in their care.

(5) The WHO discontinues the hospital arms of both hydroxychloroquine and lopinavir/ritonavir trials, on the grounds that they statistically are no better than standard of case.

Contrary to the misleading headline in the original, however, it seems that the shutdown only affects the hospital arm, and that the prophylaxis and outpatient arms of the trials are continuing. I would indeed not expect antivirals like lopinavir/ritonavir (and, indirectly, HOcq) to be very effective in the severe disease stage, at which point immune overresponse is your biggest threat, not the virus per se anymore.

ADDENDUM: David Friedman on the recent increase in verified cases not being accompanied by an increase in deaths.

COVID19 update, July 8, 2020: by CDC criteria about to fall below “epidemic” threshold in the USA?; Israel public health chief resigns, citing “frivolous” decision making process; Dr. Campbell on knowns and “known unknowns” of COVID19

(1) Instapundit reports that the death rate from COVID19 has fallen far enough that by CDC criteria it’s about to fall below the “epidemic” threshold. He comments:

WE CAN HOPE: Is The Pandemic Coming To An End At Last? “Well, firstly, it’s not actually us saying this. It’s the Centers for Disease Control, which reported that the death rate has fallen so far it’s now roughly equal to the threshold for even qualifying as an epidemic, which isn’t as severe as a pandemic.”

Death rates aren’t following case numbers up, at least not yet. In my area we had our first Covid deaths in two months last week, as case numbers climb — but we’ve had a total of 9 deaths in a county of over 400,000 people since the beginning of the pandemic. We’ve almost certainly lost more people to flu in the same period.

But case numbers are climbing, and death is a lagging indicator. Even so, though, if the disease is as fatal as it was in, say, March, deaths should be climbing much faster than they are. Some of that is no doubt because we don’t have the nursing home outbreaks we had back when Grandma-Killer Cuomo and other governors were sending infected patients into nursing homes, and some of it may be because Vitamin D levels are higher this time of year, and coronavirus fatalities seem closely tied to very low Vitamin D levels. Also, thanks to the marches and the general laxity that followed them, more of the infected are younger people, who typically don’t get as sick. That’s good, because it’s moving us toward herd immunity with as few fatalities as possible. But stay tuned; it’s still too early to know what’s really going on.

(2) Despite that, Israel is seeing a second wave of the same magnitude as the first, but again (tellingly) with much lower mortality than the first. Still, our country’s head of public health, Prof. Siegal Sadetski (on leave from Tel-Aviv U.’s medical school) suddenly resigned, and left a blistering public resignation letter.

In the letter sent to Health Ministry director-general Chezy Levy, she accused the government of “making frivolous and unsubstantiated decisions, without considering their widespread and long-term public health implications.” 

“Infinite time” is spent “calming the spirits” and “managing partnerships,” while the work that needs to be done in the field is relegated, Sadetsky said.

“Too much time is invested in debates, discussions, consultations and forums… while the operations and details required for the success of the various operations do not receive the proper attention,” she said, stressing that the work environment at the Health Ministry has become wrought with personal interests. 
“The [coronavirus] is a deadly, cunning and agile epidemic,” she added. “I feel with a high-level of certainty… that the coming months will be difficult and even tragic.”

[…] “Opening the education system first in a limited way and two weeks later in a sweeping way… led to widespread reinfection in Israel,” Sadetsky said. “Maintaining educational frameworks plays a major role in the ability to safeguard the economy and their importance to our children. However, in the absence of conformity to corona regulations, schools and kindergartens become fertile grounds for infection. 
“Israel opened the education system too quickly compared with most countries in the world. Without compatible conditions, education systems cannot be opened.”

“In the first phase, Israel’s achievements were reflected in the flattening of the morbidity curve, and the measures taken were inspirational and praised by other countries dealing with the plague. In contrast, the second phase was characterized by a vital but rapid and sweeping opening of the economy […] The atmosphere of illness treatment and decision-making has changed fundamentally, and the results are evident in the morbidity curve,” Sadetsky said. 
The government broke its promise of opening progressively and reviewing the impact of its decisions, continually moving forward even though the morbidity graph indicated the situation was getting worse, she said.

“The global experience in dealing with epidemics shows that actions and moves that are avoided due to the fear of difficult and painful decisions subsequently cost twice as much as making those difficult decisions,” Sadetsky wrote. “It was only last weekend that [the government] decided it was ready to return to preventative measures, which in my estimation is too little and too late.”

Another article in the Jerusalem Post (which sadly has gone downhill under its new editor) uses the term “ship without a rudder” and contrasts the clear voice with which authorities spoke during the first wave with the chaotic mess currently pertaining. 

The decision-making process is actually more complicated than the public is aware: Some decisions fall into the hands of the Health Ministry, some are the government’s and still others the Knesset’s, which means that even though the new directives were announced together, only some of them went into effect. 
“Sometimes, the directives are in the news, but they are not yet enforceable,” clarified Prof. Hagai Levine, a Hebrew University epidemiologist and chairman of the Israeli Association of Public Health Physicians.

But whether the directives are enforceable or not should not be a question for the public, he said, adding: “If the risk of attending a mass wedding is high, then regardless of the law, you should not organize such a wedding.” 
Nonetheless, Levine admitted that when it is unclear to the public that the decisions made by the government are based on science, rather than pressure by the loudest interest groups, it harms public trust and makes it harder for the people to follow them.

The current national unity government with its proliferation of redundant ministerial portfolios created explicitly for coalition reasons, led to the quip “we have more ministers than patients on respirators”.

In other Israel-related COVID news, El Al, Israel’s national airline which was privatized 15 years ago, is being renationalized. The company was struggling to begin with, but now was brought to its knees like many national airlines.

(3) I’ve been wanting to do a “Known knowns, known unknowns, and unknown unknowns about COVID-19” post for a while. This just-released video by Dr. John Campbell is a good starting point though.

For the impatient, there are some keyword-style talking points in the description of the video, which also links to two articles:

https://www.nature.com/articles/d41586-020-01315-7

https://www.nature.com/articles/d41586-020-01989-z

Watch the whole video (on high-speed if need be — I often run such videos at 1.25 or 1.50 speed) but I just want to highlight one aspect I haven’t ever discussed here. 

(a) viral load (around 11 minutes into the video). Paraphrasing: Ten viral particles or so might be enough to get to the throat, but are likely to be cleared by the mucociliary system. By the time viruses from the throat infection can make it down to the lungs, the innate immune system, the rapid-response part of the body’s immune system, has mobilized. For such people, it would end with a mild case.

In contrast, you get a hundred viral particles or so, and some may make it past the mucociliary system down to the lungs before immunity has had a chance to mobilize — setting you up for pneumonia and a severe case. 

(b) genetics (about 21 minutes into the video): 4,000 people in Northern Italy who got particularly bad seem to belong to two particular gene variants. There are precedents for this in, e.g., the bacterial disease tuberculosis and the viral disease Epstein-Barr. 

BEFORE I FORGET: This other video by Dr. Campbell, which is mainly about face coverings, also has a cute memory trick for the different kinds of immunoglobulins:

IgM for iMMediate action

IgG for aGGlutinating

IgA for sAlivA, sweAt, and teArs (or mucous membrAnes)

IgE in type 1 hypersEnsitivity

COVID19 update, July 6, 2020: mortality lower than generally perceived; easier to synthetize alternative to remdesivir? Tightened restrictions in Israel

(1) “Masgramondou” sent me the following:

https://www.wfae.org/post/wake-forest-covid-study-death-rate-severity-symptoms-lower-first-thought

A study by Wake Forest Baptist Health has found that between 12-14% of people tested in North Carolina have antibodies for the coronavirus — meaning they have been exposed to the virus — with most of them showing little or no symptoms. 

The majority of the study participants are in the Triad area. 

The findings suggest that COVID-19 is less deadly than originally thought and that the death rate for the disease could be in the range of 0.1%.

But the study also shows that there is significant community spread and that efforts so far to curtail COVID-19 are faltering. 

“It’s a double-edged sword,” said John Sanders, the chief of infectious diseases at Wake Forest Baptist. “We are clearly seeing a rapid increase in the number of people that we have antibody evidence who have been infected.”

But he said “the vast majority of these people have very few or no symptoms.”

“We can look at it and say the death rate is lower than we have estimated,” Sanders said. “The severity of symptoms is lower than we estimated and the vast majority of people who were infected are going to do fine.”

[…]

There are about 10.5 million people in North Carolina. If 14% of the population has been infected with the coronavirus, that would translate into about 1.47 million people.

The state has more than 66,000 confirmed cases as of Wednesday and 1,373 confirmed COVID-19 deaths.

Stanford U. Professor John Ioannides, a medical doctor and statistician best known for his research Into the reliability and reproducibility of the medical literature, points out that mortality for those below 45 is “almost zero”, and slams statewide lockdowns. (I approve of lockdowns as a targeted measure in densely populated areas, but don’t believe in their use as blunt instruments.)

“The death rate in a given country depends a lot on the age structure, who are the people infected, and how they are managed,” Ioannidis said. “For people younger than 45, the infection fatality rate is almost 0%. For 45 to 70, it is probably about 0.05%-0.3%. For those above 70, it escalates substantially.”

[…]

Several states have seen spikes in cases, especially in the southeastern part of the country, where lockdown measures were lifted earlier than in other states.

The mortality rate nationwide appears to be tapering, however, a trend U.S. health officials attribute to a younger age bracket in terms of infection. The national single-day death rate from the virus fell to a three-month low last month. Additionally, Massachusetts reported zero new deaths from the coronavirus on Tuesday for the first time since March.

(2) From an ACS virtual issue of COVID-19 related articles across its journal family, this one caught my eye:

https://doi.org/10.1021/acsmedchemlett.0c00316

Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment
Victoria C. Yan* and Florian L. Muller

While remdesivir has garnered much hope for its moderate anti-Covid-19 effects, its parent nucleoside, GS-441524, has been overlooked. Pharmacokinetic analysis of remdesivir evidences premature serum hydrolysis to GS-441524; GS-441524 is the predominant metabolite reaching the lungs. With its synthetic simplicity and in vivo efficacy in the veterinary setting, we contend that GS-441524 is superior to remdesivir for Covid-19 treatment.

(3) Was the lockdown worth it? The Daily Telegraph has a long piece in which twelve experts and writers of the paper make their cases pro and con.

(4) Israel, with escalating COVID-19 infections in what is probably the one pronounced second wave at the moment, announced tightened restrictions. Prof. Eli Waxman, head of the Coronavirus ad hoc committee, speaks out in this interview. This needs to be seen in the context of a tug-of-war between public health authorities fiercely defending their own turf, and perceived “upstarts” with “no background in medicine” (never mind what they can bring to the table in terms of logistics, tracing, and testing knowhow). A somewhat similar situation pertained in the US at least at the beginning of the outbreak, where it often seemed the CDC was excessively preoccupied with protecting its own backyard — particularly on testing, whic Germany wisely decentralized from the beginning.