COVID19 update, April 3, 2020: what does Iceland‘s unique dataset tell us?

Iceland is a small island nation with a thriving biotech industry. As such, it adopted a (to my knowledge) somewhat unique strategy: aside from contact tracing measure, local biotech company deCODE (an AmGen subsidiary) allows anyone who shows up to be tested. (This type of “big data” gathering seems to be part of their business model: they also did genetic testing for about half the adult population in the past https://www.decode.com/research/ )

As of the time of writing of this article https://www.businessinsider.com/iceland-coronavirus-pandemic-approach-could-help-other-countries-2020-4 about 20,930 people, i.e., 6% of the total population got tested — by far the highest proportion of tests in the population anywhere. (For perspective: to reach the same amount of coverage in the US you’d need to test about 20 million people. The US has tested about 1/20th of that number. https://covidtracking.com/data/ )

As of this morning, Iceland has 1,319 cases, of which 4 (four) people have died, 44 people are hospitalized (12 of them in ICU), and 1,031 are in home isolation. 284 have recovered from the infection. 7,166 people are currently in quarantine, 8,945 have completed quarantines.

https://www.covid.is/data

Now beware of comparing apples with oranges: the official government COVID19 page for Iceland https://www.covid.is/data speaks of 1,319 infections, not sick people. (It appears Israel similarly counts everybody who tests positive as a patient.) So the apparent enviably low 4/1319*100%=0.3% is really an IFR (infection fatality rate), not a CFR (case fatality rate).

[Iceland’s chief epidemiologist Thorolfur] Guðnason is quoted here

https://futurism.com/neoscope/half-coronavirus-carriers-no-symptoms as saying “Early results from deCode Genetics indicate that a low proportion of the general population has contracted the virus and that about half of those who tested positive are non-symptomatic.”.

Note, Iceland did not engage in any lockdowns — gatherings over 25 are forbidden, but otherwise economic life goes on. Instead, aggressive test & trace and quarantines are the order of the day. While the country’s low population density might seem to help, nearly two-thirds of the population is concentrated in and around the capital Reykjavik — which especially by US standards is fairly dense.

Elsewhere I read that not only was Iceland able to trace the source of the infection in most cases, but even to distinguish between different mutants of the virus. https://edition.cnn.com/2020/04/01/europe/iceland-testing-coronavirus-intl/index.html

“We can determine the geographic origin of the virus in every single [virus] in Iceland,” he said, adding there are specific, minor mutations for the virus that came from Italy, Austria and the UK. “There was one that is specific to the west coast of the United States,” [Stefansson] added.

[He] wonders whether mutations in the virus are “responsible, in some way, for how differently people respond to it — some just develop a mild cold, while some people need a respirator,” or whether a person’s genetics dictates their condition. “Or is it a combination of these two?” he asks.

“Keep in mind that the screening is now randomized, but voluntary so there is some bias in the data,” the Directorate of Health said in a statement, adding that a “randomized screening program has started and a blood serum screening for antibodies is planned.

COVID19 update in brief, April 2, 2020: (1) Belgium followup; (2) German RKI recommends masks for everyone, Israel mandates them in public

A very busy day at the (remote) day job, so just a brief update:
(1) Following up on the earlier report from De Standaard (in Dutch) reports a grim peak of 183 dead in a single day, for a total of  1,011 in a country with 11 million people.

However, and this is the good news, hospital admissions have held steady between 450 and 650 for the past week. The last day, 584 new admissions were offset by 363 discharges. Out of 5,376 hospital patients with COVID19, 1,114 are in ICU, an increase by 56 (the smallest since March 23). 906 of those need ventilation, an increase by 72.

teven Van Gucht, head of the National Corona Committee, is quoted as saying, ‘The nummer of new admissions fluctuates already for days in the same range, which indicates we’ve reached a plateau. This is surely due to the [social distancing] measures.”

A friend sent me this graph. Note that both the graphs for Belgium and for Israel show a noticeable “inflection point” around 14 days beyond the introduction of social distancing measures.

(2) While Belgium is still reluctant to mandate masks for everyone, Germany’s authority for infectious diseases, the Robert Koch Institute (named after the discoverer of, among others, the tuberculosis bacillus) now recommends masks for everyone. Their prime benefit is said to be stopping asymptomatic infection carriers from spreading the disease.
For the same reasons, Israel’s ministry of health today mandated the wearing of masks in public areas.

COVID19 update, April 1, 2020: not April Fools edition

(1) Dutch scientists discovered that SARS-nCoV-2 can be detected in a city’s wastewater even before anybody realizes they are sick. “[Medema and coworkers] detected genetic material from the coronavirus at a wastewater treatment plant in Amersfoort on March 5, before any cases had been reported in the city, located about 50 kilometers (32 miles) southeast of Amsterdam. “

(2) Chemical and Engineering News, the house organ of the American Chemical Society, has more on remdesivir as well as on another antiviral discovered at Emory, EIDD-2081. While remdesivir needs to be administered intravenously, EIDD-2081 can be given orally. On the other hand, EIDD-2081 hasnever been tested in humans while remdesivir underwent safety testing back in 2015 (as a potential ebola drug.

(3) WIRED has a long story about masks. “Let’s face it: they work”. Most of the evidence concerns other respiratory viruses:

“A 2011 review of high-quality studies found that among all physical interventions used against respiratory viruses—including handwashing, gloves, and social distancing—masks performed best, although a combination of strategies was still optimal.”

Fortunately, the available evidence suggests that for most people in most situations, an N95 is not a necessary form of protection against Covid-19. If we eventually have a surplus of surgical masks, which are much more comfortable and affordable than respirators and still provide excellent protection, they would be an ideal choice for universal masking. In the meantime, homemade masks made from tightly woven yet breathable fabric are the best option and certainly better than nothing. A piece of cloth will never be as good as a manufactured filter, but it can still smother the brunt of a cough or sneeze and impede other people’s respiratory droplets.

Read the whole thing.

Ideas-spanishflu-50599275.jpg
Seattle police during the 1918 “Spanish flu” pandemic

(4) According to a new epidemiological analysis in British medical journal THE LANCET: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30243-7/fulltext the infection fatality rate (IFR) of COVID-19 is 0.657% (confidence interval 0.389-1.33 %) and the adjusted case fatality ratio (CFR) is 1.38% (confidence interval: 1.23-1.53%). [mention in MSM: https://nypost.com/2020/03/31/covid-19-death-rate-lower-than-previously-reported-study/ ]

(5) Beijing’s “mask diplomacy” appears to be backfiring, as many of the masks and test kits sent out turn out to be defective or substandard.

“Spain’s health ministry last Thursday said it had withdrawn around 58,000 Chinese-made test kits after it emerged that they had an detection accuracy of just 30 percent. The normal accuracy rate is more than 80 percent, local media reported.”

The story of a shipment of 600,000 mouth masks for healthcare workers being disapproved by the Dutch authorities as not meeting basic quality standards is all over the Dutch-language media, e.g., here in De Telegraaf.

(6) GenomeWeb reports that a genetic cancer testing company, that has seen demand slump as “non-urgent” medical tests are put off due to COVID-19, is now retooling for COVID-19 testing.

(7) Israel starts passive immune therapy experiment. This happened only today, as they needed a plasma donor who was not only cured, but had subsequently tested negative for the virus at least twice.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Below follow my notes from the video:

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

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

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

Full interview with Dr. Kim Woo-Ju