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.

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.

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”

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, 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

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.