COVID19 update: March 23, 2020. What's in a name?

A reader asked me whether the scientific name is coronavirus, COVID-19, or something else. Without getting into the dispute over the common names, let me address that question specifically.

In a nutshell, coronaviruses are one major family of viruses. What they all have in common is their structure: They consist of a single strand of RNA which encodes the genetic “payload” , a shell of envelope proteins self-assembling around the strand, and a bunch of spikes on the shell whose job it is to stimulate receptors in the cell wall and effect an opening for entry. The spikes look like a kind-of ‘crown of thorns’ under an electron microscope, hence the name ‘coronavirus’.

The most common subgroup humans get exposed to are one type of common cold viruses (although most common colds are caused by rhinoviruses, a different family). There are other coronaviruses that are endemic in poultry and cause upper respiratory tract infections there. Others are endemic in bats, etc.

Alas, some coronaviruses are quite deadly to humans: SARS-nCoV (severe acute respiratory syndrome, novel coronavirus), also known as SARS-CoV, is the one that causes the disease simply named SARS. Originating in horseshoe bats, it somehow crossed the species border and caused a nasty epidemic in mainland China and Hong Kong, with another outbreak hitting Toronto hospitals. CFR (case fatality rate) of the disease is very high, at 9.6%, but no overt cases have reportedly been seen since 2004.

Another is MERS-CoV, causes MERS (Middle East Respiratory Syndrome, one colloquial name being “camel flu”). It apparently crossed the species barrier from bats to camels and thence (possibly via camel-based food products) to humans. MERS has a very high CFR (case fatality rate) of about 1/3 of diagnosed cases, but has a very low reproductive number (in part because it is so deadly?): since it was first described in 2013, we’ve had only about 2000 cases ever worldwide. An outbreak in South Korea in 2015 when a businessman returned from the Arab peninsula appears to have been when the South Koreans got their ‘dress rehearsal’ for how to deal with the present emergency.

The present virus is known as SARS-nCoV-2 because its RNA sequence is so similar (82 % sequence identity) to SARS-nCoV. The mutations that make up the difference (single-strand RNA viruses mutate very rapidly — for reason I’ll explain elsewhere) appear to have had two primary effects: (1) the virus is less deadly; (2) the spikes are more efficient at stimulating ACE2 receptors (angiotensin-converting enzyme 2), which it exploits to enter cells. (Remember, a virus that cannot enter a cell and take over its replication machinery can’t do much of anything. Like a computer virus without a computer ;))

What happens once the virus is inside, by the way? The RNA goes to a ribosome, which are the cell organelles that acts as  protein ‘assembly plant’ of our cells. Gene expression in our cells involves chunks of DNA getting copied onto “messenger RNA”, which then makes its way to the ribosome and gets translated into a protein (by assembling amino acids according to what the “tape” says, until it hits what biologists call a “stop codon”: an “end of message” marker, so to speak). When the viral RNA enters the ribosome instead, that merrily carries out the work order written on the “imposter”, such as the enzyme needed to clone the viral RNA (RdRA, or RNA-dependent RNA polymerase), the envelope proteins, and the spike proteins. There is considerable speculation that the spike proteins in SARS-nCoV-2 are more effective than those in SARS-nCoV.

COVID-19 (coronavirus disease, [first outbreak in] 2019) is what WHO settled on as the name for the disease, not the agent.

UPDATE: statistician and software developer Charlie Martin weighs in more on the Italy data.
And a Japanese financial website reports that the campaign to get the residents of Wuhan to “thank” their dictator backfired badly.
Also, some signs that maybe the anomalously good statistics from Japan may be the product of selection bias: see here (especially the comments) and here. One of the articles, however, made a collateral point I’ve brought up here before:

Cases of seasonal flu have been declining for seven straight weeks, just as the coronavirus was spreading, indicating Japanese may have taken to heart the need to adopt some basic steps to stem infectious diseases. Tokyo Metropolitan Infectious Disease Surveillance Center data shows that influenza cases this year are well below normal levels, with nationwide cases hitting a low according to data going back to 2004.


Also, after Sen. Rand Paul (R-KY), German Chancellor Angela Merkel is the latest politician to go into 14-day quarantine after the doctor or nurse who gave her a standard flu vaccine tested positive for COVID-19.

UPDATE 2: leaked documents appear to indicate that the claim that “there are no new cases in Wuhan” needs to be taken with LOTS of sodium chloride.

UPDATE 3: on the other hand, there is some good news hidden in all the bad (via Instapundit):
And this one gets the Möbius Dick Award: NYT claims travel restrictions didn’t work in China — for the period they weren’t implemented

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

RIP Li Wenliang, one of the “Fallen Caryatids”

Dr. Li Wenliang, the Chinese doctor who first warned a major epidemic of a new coronavirus was afoot (and suffered police intimidation for doing so) has now succumbed to the disease. May his memory be for a blessing.

My writing mentor Sarah Hoyt’s immediate reaction was “Rodin’s Fallen Caryatid”. [See also her own blog post.]

Auguste Rodin, “Fallen Caryatid With Stone” [ CC:BY Emw ]

She recalled its description by Robert Heinlein. Verily, it is hard to think of a more fitting tribute, to him and so many others like him.

[Jubal Harshaw to Ben:] “[F]or almost three thousand years or longer, architects have designed buildings with columns shaped as female figures—it got to be such a habit that they did it as casually as a small boy steps on an ant. After all those centuries it took Rodin to see that this was work too heavy for a girl. But he didn’t simply say, ‘Look, you jerks, if you must design this way, make it a brawny male figure.’ No, he showed it . . . and generalized the symbol. Here is this poor little caryatid who has tried—and failed, fallen under the load. She’s a good girl—look at her face. Serious, unhappy at her failure, but not blaming anyone else, not even the gods . . . and still trying to shoulder her load, after she’s crumpled under it.

  “But she’s more than good art denouncing some very bad art; she’s a symbol for every woman who has ever tried to shoulder a load that was too heavy for her—over half the female population of this planet, living and dead, I would guess. But not alone women—this symbol is sexless. It means every man and every woman who ever lived who sweated out life in uncomplaining fortitude, whose courage wasn’t even noticed until they crumpled under their loads. It’s courage, Ben, and victory.”
“Victory?”
“Victory in defeat, there is none higher. She didn’t give up, Ben; she’s still trying to lift that stone after it has crushed her. She’s a father going down to a dull office job while cancer is painfully eating away his insides, so as to bring home one more pay check for the kids. She’s a twelve-year old girl trying to mother her baby brothers and sisters because Mama had to go to Heaven. She’s a switchboard operator sticking to her job while smoke is choking her and the fire is cutting off her escape. She’s all the unsung heroes who couldn’t quite cut it but never quit. Come. Just salute as you pass her[…]

Robert A. Heinlein, “Stranger In A Strange Land”, Chapter 30.