COVID19: March 21, 2020 update

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

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

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

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

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

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

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



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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

FDR, inaugural address (1933)

UPDATE: via Behind The Black,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A brief Coronavirus update

A guestblogger at Watts Up With That, who himself survived the infection, has a news-packed update. Read the whole thing, but perhaps the most important paragraphs are:

Transmission route is either contact or inhalation […] The significant inhalation route is now shown by both the Diamond Princess cruise ship experiment (more below) and by the fact that ordinary surgical masks proved ineffective in the Wuhan hospital setting (JAMA, previous post).

Incubation period is 7-10 days from initial infection. The good news is that the 14-day quarantine adopted pretty much universally last week should therefore be effective […] Wuhan then makes a now well-established clinical bifurcation. In 75-80% of cases, by symptom day 10 there is a normal ‘corona cold’ recovery lasting a few days. (In my own case last week, 3 recovery days in total, days 9-12 from symptom onset.) In 20-25% of cases, by symptom day 10 Wuhan progresses to lower respiratory tract pneumonia, where death may occur with or without ICU intervention. The percentage of these deep pneumonias that are viral as opposed to a secondary bacteria infection is not known, but the NEJM clinical case report from Washington State discussed in the following paragraph strongly suggests viral (like SARS), not secondary [opportunistic] bacterial [infection] treatable with antibiotics.

The bad news is that Wuhan IS transmissible during some later part of the symptomless incubation period. […]

And here is some good news:

The new NEJM [New England Journal of Medicine] case report is so important it is summarized here because it leads to a hopeful culminating section below. The Seattle Wuhan case evidenced x-ray diagnosed lower respiratory tract pneumonia from days 9-11 from symptom onset. Supplemental oxygen was started day 9. IV antibiotics were started day 10 to no effect, so discontinued after one day. Importantly (more below), experimental antiviral remdesivir started day 11 by IV under a compassionate use exception, and the deep viral pneumonia fully resolved (per x-ray diagnosis) within 24 hours!

Remdesivir was developed by Gilead Scientific as an antiviral for Ebola and Marburg viruses, but was subsequently found to be active against other single-stranded RNA viruses.

Based on this, China has announced a full-scale random double blind placebo controlled trial in 761 patients. As of this writing China reports successful synthesis of sufficient remdesivir active, so human testing begins today.

PS: A friendly writer sent me this rather more worrying analysis arriving at a comparatively high basic reproduction number R0 of the virus: https://www.medrxiv.org/content/10.1101/2020.02.07.20021154v1