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 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.

 

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 20, 2020: reinfection unlikely; correlation between HbA1C and vulnerability to severe disease; German RKI recommendations on masks

Just a quick update today, as workday has been pretty intense.

(1) Dr. John Campbell’s vlog has a special edition on a new report from the South Korean CDC. There have been a number of worrying reports that people tested positive again after recovering, fueling speculation that this could become a chronic disease, like HIV or Hepatitis B. (As he explains, these viruses slip into the cell nucleus and insinuate themselves into the human genome.[*]) Worse, that people could be infectious for life.

However, as it turns out, the tests were false positives. The RT-PCR test detects the presence of a short fragment of RNA that’s specific to the virus, but cannot tell whether this is a remnant of long-destroyed virus, or belongs to a viable virus particle. So when cured patients cough up worn-out lung cells in their sputum, such remnants will trigger a false positive test. This appears to have been the case here.

https://www.youtube.com/watch?v=uATMbGK__Tg

Just as I was typing today’s update, Dr. Seheult posted a video on the exact same study. He has the link to the English version of the Korean CDC report in the description. (Dr. Campbell had to go off second-hand reports, as only the Korean-language version had been released at the time.) Dr. Seheult’s video adds much more detail.

https://www.youtube.com/watch?v=01Rftnxbi6w

I believe this is the great COVID19 news of the day.

(2) Yesterday, the good doctor posted another video with a couple of different segments. One is about a recently published evaluation of four new antibody tests using arrays of known positive and negative samples. http://doi.org/10.1016/j.jcv.2020.104394 “Comparison of Four New Commercial Serologic Assays for Determination of SARS-CoV-2 IgG”

The second is about a paper in the Journal of Diabetes Research, showing a clear link between high levels of glycosylated hemoglobin (high HbA1C values) and severe COVID19. http://doi.org/10.1016/j.diabres.2020.108214 “Glycosylated Hemoglobin Is Associated With Systemic Inflammation, Hypercoagulability, and Prognosis of COVID-19 Patients”

https://www.youtube.com/watch?v=UANgon3Umns

Those of you who are struggling with diabetes (or are trying to avoid going there, as I am) will recognize HbA1C — while blood glucose gives an immediate picture, HbA1C gives an “integral”, as it were, of your blood sugar picture over the last few months, and is less prone to fluctuation due to exertion or recent food or drink intake. [**]

(3) Recently, the topic of face masks has generated extreme passions on both sides, at least in the US. (In Israel, the mask mandate came about as a compromise between the Ministry of Economics, which pushed for accelerated reopening of stores, and the Ministry of Health which wasn’t keen on that. The latter acquiesced in exchange for getting its way on masks. As far as I can tell in my Tel-Aviv borough, the mandate is not being enforced visibly, and indeed in some places is honored more in the breach than the observance.)
Now I would like to think that both sides in the US debate would agree that Germany doesn’t mess around in such matters. (Besides, its statistics in the epidemic speak for themselves.) So what does the Robert Koch Institute (RKI) — their infectious diseases authority — have to say on the matter? Here is their position paper on the subject, which may surprise both the “no masks!” and “must wear masks, because science!” sides. Summarizing in translation:

• most important are good hand hygiene, sneeze-cough hygiene, and maintaining an effective distance of 1.5m (5ft)
• high-grade multilayer masks are foreseen for healthcare workers
• we recommend keeping a simple textile mask handy to wear in specific situation in public, namely where no 1.5m distance can be maintained (e.g., on public transit). [***]
• that said, some people are unable to wear masks at all due to health conditions
• links to “proper wear and care” recommendations for different mask types
• notably absent: any recommendation, let alone requirement, that people need to wear masks in public at all times

[*] What Dr. Campbell skips over is that the RNA is first copied to a double strand of DNA using an enzyme called reverse transcriptase — yes, the RT of RT-PCR testing.

[**] Our red blood cells don’t last much longer getting pumped around our bodies, and hence are continuously replaced by newly manufactured ones, with an average turnover of about 4 months.

[***] I feel compelled to belabor the point that momentary passing-by at closer distance does not mean you are suddenly at risk of infection. Our own Ministry of Health, which recommends 2m (6ft6), only counts exposure as ‘closer than the safe distance for 15 minutes or longer.

COVID19 update, April 14, 2020: vitamin D, zinc, testing; end of globalization as we know it?

(1) Roger Seheult MD in his latest update gives a clear discussion of RT-PCR (reverse transcriptase polymerase chain reaction) testing vs. antibody testing.

I spoke to an industry insider about why not more antibody testing yet? I was told that first-generation antibody testing kits achieved accuracies of around 30%, which are “worse than useless”. But accuracies are steadily improving, and we should soon be looking at something comparable in accuracy to a good RT-PCR.

In response to reader demand, Dr. Seheult also gives a link to a hydrotherapy regime that might be useful for prophylaxis and for treatment of mild cases — but only in addition to more conventional approaches: https://www.hydro4covid.com

(2) Nursing school instructor John Campbell, in his latest update, hammers a lot on the beneficial effect of vitamin D for the human immune system. In fact, he looks at the different mortality statistics for ethnic groups in NYC, and finds it fascinating that everybody comes up with socio-economic explanations while overlooking something obvious: at northern latitudes, vitamin D deficiency is quite common among dark-skinned people. (In fact, both the white and “yellow” skin types evolutionarily started as mutations that just happened to allow humans to thrive in less-sunny northern regions.)

He strongly recommends everybody who does not already enjoy abundant sunshine take vitamin D supplements to boost their immune systems — especially people with darker skin types.

On a related note, he looks at the surprisingly mild statistics of the epidemic in Australia, and notes that this militates in favor of seasonality — but again stresses the beneficial effect of vitamin D in the sunny Australian summer and early fall. (I note that South Africa too has so far dodged a major bullet.)

He also notes that homes for the elderly everywhere have appalling statistics — it takes only one or two cases to cause a major outbreak in one unless you really know what you are doing.

One more thing: out of 459 newly diagnosed cases in South Korea, 228 are imports from the USA. While he admits this will not be a representative sample of the US population (whoever still travels may be a businessman or some sort of expert), it does have implications for the Dunkelziffer/”dark case load” in the USA.

(3) Speaking of nutrition, a number of doctors advocate zinc supplements. [Full disclosure: I have been taking such since the beginning of the crisis.] This is emphatically not quack science: zinc is an essential nutrient, and in fact the most common transition metal in the body outside the bloodstream. (Iron in hemoglobin is the most common one if you include it.) Hundreds of physiological processes depend on zinc in the catalytic site of an enzyme, as a co-catalyst or modulator, or as a structural element. This includes the immune system too: I was struck between the similarity between some early COVID19 symptoms (such as loss of taste and smell) and those of zinc deficiency (presumably because Zn is mobilized in great amounts for the immune system). Here is an academic review article on the roles of zinc in the antiviral immune system.

Particularly people who live on vegetarian diets are at risk for Zn deficiency — those who primarily live on red meats or seafood least so.

(4) Urban geographer Joel Kotkin, in a must-read essay , explains how COVID19 (and whatever similar epidemics may lay in our future) will make dense urban centers less attractive to live in. He notes NYC accounts for nearly half of COVID19 mortality in the USA, greater Milan for half the cases in Italy and almost 3/5 of deaths,… “Simply put, pandemics are bad for dense urban areas, particularly those that are diverse and relatively free. This has been very much the case since antiquity. The more global and vital an urban system—Rome, Alexandria, Cairo, Venice, Florence, London, Paris—the more susceptible it is to the pandemics that seem to be occurring regularly over the past two decades. Cities no doubt will recover, particularly if real estate prices continue to fall, but the pandemics limit their upward trajectory and will continue to drive people elsewhere.”

On a related note, former director of the World Bank’s research department Branko Milanovic, https://www.standaard.be/cnt/dmf20200327_04904960 interviewed in De Standaard (in Dutch) argues that (my paraphrase) “We went for the extremes of globalization because technology enabled it. COVID19 showed such an economy is brittle.” He does see a return to some form of globalized economy the day after the crisis, but not again to this extreme extent.

It is noteworthy that such “the end of globalization as we know it” rhetoric is not the province of just the American populist “right”, but that one can hear similar voices around the globe and the political spectrum from the German establishment center-right to the left. I was (pleasantly) surprised to read a scathing article in The Guardian (!!) about the way some Chinese academic publications about the origins of the virus had to be airbrushed by CCP regime fiat. “Oceania is not at war with Eurasia.” [On a related note, Taiwan released an Email from December in which it warned the WHO about patients with a new, SARS-like lung disease.]

The American Interest looks at the long, hard road to decoupling from China. An article in De Standaard (in Dutch) entitled “[shoddy m]asks as a canary in the coalmine”, looks at the trend towards what it calls with an English neologism “reshoring” — bringing production back home to have better control over supply chain and especially quality. This process is said to have been going on for a while in Belgium, but is now being accelerated by COVID19.

Finally, feelgood story of the day: at age 107, a Dutch woman named Cornelia Ras is now the oldest person to survive a bout with COVID19 .