COVID19 update, September 16, 2020: Paracelsus says “the poison is in the dose” edition

All things are poison, and nothing is without poison, the dosage alone makes something not be a poison.

Paracelsus. (Original wording: Alle Dinge sind Gift, und nichts ist ohne Gift, allein die Dosis macht dass ein Ding kein Gift ist.)

I couldn’t help thinking of this when viewing Dr. Campbell’s latest video.

It also discusses a few other subjects. One is anecdotal evidence that Anthony Fauci MD is taking high doses of vitamin D supplements (as I myself have been doing at, among others, Dr. Campbell’s urging). Another is progress with vaccines: supposedly the United Arab Emirates (which, together with fellow Persian Gulf state Baḥrain, just signed the historic Abraham Accords with Israel) completed Phase 3 trials with a Chinese vaccine (an old-school attenuated-virus vaccine, not an mRNA vaccine like Oxford/AstraZeneca) and have given emergency approval for the vaccine.

But the top story is a new “perspective article” in the New England Journal of Medicine (about which ‘masgramondou’ tipped me off earlier): “Facial Masking for Covid-19 — Potential for “Variolation” as We Await a Vaccine” by Monica Gandhi, M.D., M.P.H., and George W. Rutherford, M.D.

https://doi.org/10.1056/NEJMp2026913

There has been increasing evidence that the “inoculum”, i.e., the viral load of infection, determines the severity of the disease: this is not unique to COVID19, by the way, nor to viral diseases. Actually, this is the mechanism of the pre-vaccine technique known as variolation: in China and the Middle East, people would be deliberately exposed to a small amount of pus of a smallpox sufferer, thus to induce a mild case of the disease and subsequent immunity. This technique was adopted in England in 1721 by an aristocratic woman who had seen it in action during a visit to Istanbul. (True vaccination — in this case, exploiting cross-immunity with cowpox — wouldn’t be introduced by Edward Jenner until nearly 1800.)

Many people mistakenly think of infection as a binary state: either you get one or a few viral particles in and you’ll get sick and (Heaven forbid) might die. In fact, if you get in a small dose of a viral pathogen, the body’s rapid-response immune system may well eliminate it before you even have a chance to feel sick. (An RT-PCR test for the said virus’s RNA may, however, well test positive!) Think of it that way: in the pre-hitech era (say, during World War Two) if your defense lines were breached by a small force of platoon or company side, it would be quickly repelled or eliminated, while a breakthrough by a division, let alone an army corps (consisting of several divisions), would be much more of a headache.

This same “all or nothing” thinking informs much of the public thinking about masks, which particularly in the US has become nearly “tribal binary” — people tend to either fetishize them (and shame other for not wearing them, even in environments where they are really not needed) or to denigrate them on the ground that cloth or surgical masks are way too porous to block viruses. (N95 masks can stop viral droplets, but can hamper breathing if you are not used to wearing them. Several companies now offer bactericidal and viricidal masks, which I have discussed here before.)

The above-mentioned paper paints a more nuanced picture: yes, masks have value in protecting others against you (unless there is enough distance and fresh air that it is unneeded) — but they also reduce the viral load, the inoculum, should an infected person expose you, and they thus increase the chance that you will get off cheap with an asymptomatic or minimally symptomatic infection. Quoting from the article:

If the viral inoculum matters in determining the severity of SARS-CoV-2 infection, an additional hypothesized reason for wearing facial masks would be to reduce the viral inoculum to which the wearer is exposed and the subsequent clinical impact of the disease. Since masks can filter out some virus-containing droplets (with filtering capacity determined by mask type),2 masking might reduce the inoculum that an exposed person inhales. If this theory bears out, population-wide masking, with any type of mask that increases acceptability and adherence,2 might contribute to increasing the proportion of SARS-CoV-2 infections that are asymptomatic. The typical rate of asymptomatic infection with SARS-CoV-2 was estimated to be 40% by the CDC in mid-July, but asymptomatic infection rates are reported to be higher than 80% in settings with universal facial masking, which provides observational evidence for this hypothesis. Countries that have adopted population-wide masking have fared better in terms of rates of severe Covid-related illnesses and death, which, in environments with limited testing, suggests a shift from symptomatic to asymptomatic infections. Another experiment in the Syrian hamster model simulated surgical masking of the animals and showed that with simulated masking, hamsters were less likely to get infected, and if they did get infected, they either were asymptomatic or had milder symptoms than unmasked hamsters.

Israel has had a mask mandate for months now, although I can tell mask discipline is lackadaisical and people who do wear them do not do so correctly. We do have galloping apparent infection rates now — but all told, the percentage of cases that require hospitalization is quite small, about one in forty to forty-five. (That ratio has held true for a few months now.)

In fact, I strongly suspect that the high new case numbers that have prompted our imminent lockdown (we’re the first country in the world to lock down twice) are an artifact of hypersensitive RT-PCR testing at ever increasing rates: if you know from serological studies that you have a “stealth infection rate” of 10 times the documented RT-PCR, then suddenly increasing from 30,000 to 55,000 tests per day will of course turn up more cases. I roll my eyes every day about innumerate journalists (BIRM) getting all atwitter over momentary variations in daily data. (The other week, I had to explain to somebody who ought to know better what the point of a 7-day moving average was.)

Note something about the age and gender distribution of infections:

men: blue; women: red

Yes, there are the “bulges” among teenagers and army and college ages, none of whom are much into social distancing in this culture. But the spike between ages 10-19 also decidedly skews male, which I suspect is related to the reopening of yeshivot (religious academies) in the chareidi (so-called “ultra-Orthodox”) sector. Still, shocking as the story of a Talmudic student in his mid-thirties (with no pre-existing conditions) dying of COVID19 may be, it is news precisely because it is an anomaly.

But what does a “case” really mean? (H/t: masgramondou.) If your body takes in a small inoculum and fights off the infection successfully without you even noticing it, does that even count as a disease, or as “Tuesday”? (Remember, quaint as this may sound, there are other viruses than COVID19 that our immune systems periodically need to get rid of an invasion in platoon or company strength of.) Yet, you will likely test positive on an RT-PCR test, and add to the kind of statistics that the media and politicians can lose their cool over (as they cannot distill the signal from the noise).

To be fair, though, I gather what ultimately swayed the decision makers, — including coronavirus czar Prof. Roni Gamzu who has been pushing back against a lockdown since his appointment — were reports that certain hospitals in Jerusalem and the North were transfering excess COVID19 patients to hospitals in the coastal plain that still had spare capacity in their COVID wards. (Such ‘load balancing’ is completely legitimate, but suggests the system is nearing its capacity limit.)

Finally, Dr. Campbell discusses some good news I was sent earlier by an attentive reader.

2 thoughts on “COVID19 update, September 16, 2020: Paracelsus says “the poison is in the dose” edition

  1. men: blue; women: red

    The chart is in green and blue; a bing translate gives “נשים” for women, ladies, female, so that’d be the left, or green, with the big “if” for my being terrible at not-used-in-English letters.

  2. I hadn’t heard of an 80% asymptomatic rate, and my immediate thought was that it might be an issue of testing– if it was later on, didn’t the tests get more accurate?
    Anyways.

    Here’s the study I found, I think it’s the same ship:
    https://thorax.bmj.com/content/75/8/693
    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.

    First thing I noticed was a MUCH higher infection rate than the Princess, having nearly 59% positive and 19% with symptoms while Diamond Princess had a total infection rate of 17%, 8% symptomatic.

    13 dead from Diamond Princess, so of those on board it’s 0.35% death rate. One death for the other ship, so .46%; complicating factors being that they’re different styles of cruises, and that folks with delicate health were likely to be staying home, and that the latter one is less than a tenth the size of the former.

    Also, the described procedure for the in the footsteps of Ernest Shackleton cruise sounds more like an attempt at medical isolation than universal masking:
    The first recorded fever on board the ship was a febrile passenger on day 8. Isolation protocols were immediately commenced, with all passengers confined to cabins and surgical masks issued to all. Full personal protective equipment was used for any contact with any febrile patients, and N95 masks were worn for any contact with passengers in their cabins. The crew still performed duties, including meal services to the cabin doors three times a day, but rooms were not serviced. Expedition staff helped with crew duties at meal service.

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