A new hydroxychloroquine study was published in the British journal “The Lancet” today. On the face of it, it appears to be an excellent study. It has a very large number of patients (96,032) in its observational study, and it was better matched to the recommended application of HCQ (ie early in the disease cycle), requiring people to have started treatment within two days of hospitalization.
The study clearly shows that people taking either chloroquine or hydroxychloroquine were at greater risk of death than those who did not take it. For patients taking (hydroxy)chloroquine and an antibiotic (a “macrolide”), the chance of dying increased still further.
But, yet again, the study is imperfect. There is one huge variable that is not known; additionally it fails to test the “ideal case” use of HCQ as recommended by its supporters.
The huge unknown variable is what was the selection procedure at each hospital for which patients were given HCQ and which were not? Noting that in total, out of the 96,032 patients, only 14,888 were given a chloroquine drug, either with or without an antibiotic, clearly there was some sort of decision-making and selection/qualification process at each hospital.
It seems reasonable to guess that if a person was admitted “out of an abundance of caution” with only very mild symptoms, they might have been less likely to have been prescribed the drug than if they were admitted with symptoms that gave rise to greater concern. The study does not know what the basis for administering the drug was at each different hospital from which they took numbers. Unless the decision was totally random, the results are greatly impacted by the selection-bias being used by each hospital.
We think it probable that only patients who were more unwell were offered the drug, particularly given its somewhat controversial status. This could not just skew but totally invalidate the results.
The failure to test the ideal case also remains present. The ideal case involves hydroxychloroquine being given as soon as possible, and in conjunction with zinc. The “within two days of hospitalization” is certainly much better than other studies that waited until patients were in the ICU, but we don’t know what the degree of unwellness was at the point the drug was given, and as best we can tell, no-one was given the drug together with zinc, as is the recommended practice. Supporters of the drug say the HCQ primarily acts as a conduit for the Zinc to be transported to where the virus is active, and has little or no impact by itself.
So, another study with a headline for the HCQ-haters, but in terms of actual meaningful results about the effectiveness of HCQ used as its supporters suggest, not so much.
Here are the rankings for the eight states of any size with the highest infection rates. There was no change in rankings today.
- San Marino/661 cases/the equivalent of 19,485 cases per million people
- Vatican City/12 cases/14,981 cases per million (unchanged)
- Andorra/762/9,864 (unchanged)
- Iceland/1,803/5,287 (unchanged)
Here are the top six major countries, showing death rates per million of population in the country. :
- Belgium/9,212 deaths/795 deaths per million
- Spain/28,628 deaths/612 deaths per million
- Italy/32,616 deaths/539
- United Kingdom/36,393/536
To put those numbers into context, the death rates per million in the US/Canada are 295/166. The world average (not a very reliable number) is 43.5.
For major countries and/or outbreaks, and in general :
|US Cases/Deaths/Case rate per million||1,484,285/88,507|
|UK Cases/Deaths/Case rate per million||236,711/33,998|
|Canada Cases/Deaths/Case rate per million||74,613/5,562|
|Worst affected major country/case rate||Spain/5,868||Spain/5,991||Spain/6,030|
|Second worst country affected||Ireland/4,859||USA/4,900||USA/4,073|
I Am Not a Doctor, But….
There’s nothing worse than paying for a test and going through the hassle of being tested, only to be given the wrong result at the end. When the result is for something “important”, your life changes. In the case of Covid-19, you might be required to lockdown and self-quarantine, or you might be told you are clear when you’re not, and you go and infect other people.
So we are glad to see the FDA is now starting to ban unreliable tests, but we have a question. What consequences do the makers of unreliable tests face? Our guess is there is no consequence whatsoever. It isn’t enough to just require such tests to be withdrawn; there needs to be a negative consequence to discourage the testmakers/marketers from doing the same again in the future.
Here’s an interesting article – one of a growing number – suggesting a link between insufficient Vitamin D and catching the Covid-19 disease.
This article, now a week and a half old, includes an interesting claim about Sweden, and adds another perspective to our somewhat downbeat evaluation of Sweden yesterday and gives us some broader optimism too.
The article claims that since mid April, there has been a drop in cases in Stockholm, which it attributes to the start of herd immunity. We have always thought that herd immunity requires 60% or more of the population to be infected in order for the herd immunity to stop the growth of the virus, but we have observed and puzzled about, everywhere in the world, how the virus infection rate slows down after surprisingly low numbers of infections (relative to the concept of 60% for full herd immunity). The worst major countries in the world have reported total case rates around 0.6%; smaller countries and regions can go up over 2.5%.
Is it possible that some measurable herd immunity kicks in at a much lower number? Does our target not need to be the seemingly unattainably high 60%?
Certainly, the whole concept of herd immunity is very much dependent on the disease transmission rate – sometimes called its “R number”. The more transmittable a disease is, the higher the herd immunity that is needed. With our social distancing measures and mask wearing and other behavior modifications, we are greatly reducing the virus’s ability to efficiently keep infecting new people. The R number is decreasing. That means we don’t need as much herd immunity to have a sizeable impact.
That is sort of reassuring, but note that if we then relax everything and return back to “the good old days” – a time which seems increasingly distant – the R rate will increase, and so too will the requirement for a higher herd immunity.
Timings And Numbers
Air travel numbers in the US have been steadily growing over the last few weeks, and surged yesterday, and reached almost 12% of last year’s number, and being the most people traveling since 25 March.
I’ll wait for the rest of the Memorial Day weekend to transpire and then post updated graphs.
One place that isn’t expecting any sudden surge of air travel is the UK. The country has now formally confirmed its plans to require all arriving passengers from other countries to self-quarantine for 14 days, starting on 8 June.
We can understand the underlying sense, but we don’t understand why Britain isn’t testing all passengers upon arrival. Surely that would eliminate the need for most arriving passengers to quarantine, or perhaps it could at least allow them then to reduce the quarantine from two weeks to perhaps one week (or shorter), and, if a second clear test was received then, it would be safe to release them from their quarantine prior to the full two weeks.
Dr Fauci is now telling us there’s a chance we might have an effective vaccine available in large numbers by the end of the year. This is based on continued promising results as several vaccine candidates progress through their trials, and the government’s decision to start producing vaccine doses for multiple “possible winners” at this early stage.
We hope he’s correct, but we do note he says this is not a probability and definitely not a certainty.
Closings and Openings
Australia has extended its ban on cruise ships through until mid September. We wonder if this is a hint of similar ban extensions in other countries too.
We’d also point out that a ban until mid September is not the same as an opening being approved for that time. Countries seem to be extending their bans for a few months at a time, and leaving open the possibility to continue extending the bans as each period nears its expiry, depending on the circumstances. So this merely tells us that the soonest cruises might restart is mid September; it doesn’t mean they will restart then.
Logic? What Logic?
It is true that there has been a conflating of two different concepts at times. When we talk about a Covid-19 test, we could be talking about one or the other of two very different tests.
One of the two tests is to determine if you have the virus at present. The other of the two tests is to determine if you have had the virus in the past. That is a very different situation. If you have the disease at present, you are probably contagious. If you have had the virus in the past, you are probably no longer contagious, and there is a possibility that you may have acquired some immunity against future re-infection.
Not only are the tests different, but the implications of their results are also different. Sometimes, it is helpful to know who has the disease at present, and it doesn’t matter at all who has had the disease in the past. Other times, it is helpful to know who has had the disease in the past, and it doesn’t matter who has the disease at present (other than as being a hint for the number of people “in the pipeline” and, assuming they survive and are cured, will add to the total at some point in the future).
For example, if you’re checking the adequacy of your hospital resources, your main focus is on people who are presently infected. If you’re trying to work out if a community is building up a herd immunity, you want to know how many people in total have had the virus at some point and now have developed hopefully immune-granting antibodies.
It is a bit like a forest fire – the fire fighters and community as a whole need to know how many acres are on fire at present, and track how many acres in total have been on fire and are now reduced to ashes.
So, with that as lengthy introduction – and while I introduced it at length to be very clear, in reality it is an extremely simple and fundamental distinction that any first year public health student immediately grasps – prepare to be astonished. Both the CDC and selected states are conflating the two tests, and creating invalid data about tests, and percentages of positive and negative results.
This reveals either stunning incompetence at a level impossible to understand, or dismayingly deliberate deception. Both interpretations are appalling.
Unfortunately, the concepts of incompetence and deception are increasingly being used to describe the CDC. We can not comprehend how an organization that should be seemingly single-mindedly focused on this mission (remember, CDC stands for “Centers for Disease Control”) is conducting itself so amateurishly and ineptly. It is staffed by people with seemingly impressive qualifications, often doctorates, and they are being richly paid for their professionalism, but they’re disappointing us repeatedly, as this article (and many others, previously) recounts.
This similar article points out further confusion with testing. The CDC and the states seem unable to agree on the actual number of tests each state is conducting. Maybe the reason is due to conflating the two different types of tests, but sometimes the CDC count is higher and sometimes the state count is higher, and sometimes there’s a 50% discrepancy one way or the other. One or two tests we could understand, but a 50% discrepancy?
This isn’t rocket science. A test is a clear specific event. There should be little or nothing subjective about counting tests, and presumably both the CDC and state health authorities are ultimately getting the same raw data from the same sources. How can they disagree so substantially? The CDC has declined to comment, so we don’t know if it is their inadequacies being exposed again, or something else.
Virus? What Virus?
Here is a very interesting article about how the virus came from bats to us. This second article follows up on and amplifies the first, earlier article. Both make good reads.
More bad news about the virus, this time reporting on how clever it is at repelling the body’s natural defenses.
And – yes – a glimmer of good news about a possible new treatment for people afflicted with severe cases of the virus. This is not an “easy” or inexpensive treatment, but if you’re afflicted with a serious case, you might be very pleased if it is offered to you.
The Dow did almost nothing today, but closed colored red rather than green, with an infinitesimal 9 point drop, at 24,465. Last week’s Friday close was 23,685, so for the week, it has climbed 3.3%, putting it also slightly above the previous week’s close at 24,331.
I mentioned in today’s regular weekly newsletter that I’d added new entries to my list of easy-to-enjoy classical music. But I omitted to include the URL where they can be found. Here it is.
I plan to continue adding entries and other related content on an occasional basis.
As our thoughts are all on next week’s first US based manned space flight in many years, and the considerable risks involved, NASA is advertising what is perhaps the safest job in the world today – going into isolation for eight months to mimic the effects of a voyage to Mars.
Unfortunately, not just anyone can apply; their list of requirements is fairly restrictive and we wonder just how many people in our country of 330 million will have both the qualifications and interest in the positions. Puzzlingly, the project is being conducted in Moscow – and no, we don’t mean the Moscow in Idaho.
Lastly for today, as the weather trends warmer, a warning. Be careful leaving hand sanitizer in your car – if it gets too hot, it might burst into flames. Not stated in the article is a secondary risk – if the alcohol evaporates out of the sanitizer and you breathe it in, then you might get a nasty surprise if stopped and tested for DWI/DUI.
Please stay happy and healthy; all going well, I’ll be back again tomorrow
Please click here for a listing of all our Covid-19 articles.
1 thought on “Covid-19 Diary : Friday 22 May, 2020”
Two comments on yesterday’s write up.
There was an excellent op-ed yesterday from two Harvard doctors on the need for more study on prevention and early treatment
The second comment is the challenges of preventative treatment studies. I’m going to do a long intro to make give some context to my comments.
I worked, as a programmer, on a large cancer research project over 40 years ago. Studying treatments for seriously ill patients is statistically rather easy especially with fast moving diseases. Sorry this is morbid but you knew with pretty high statistical certainty if a treatment for colon cancer had any impact in a matter of months since the average time between discovery and death was measured in weeks. So any positive impact of a treatment was known quickly.
The reverse is true for preventative studies. Again over 40 years ago, there were two large studies of the effect of aspirin on preventing heart attacks. There were two studies, one in a European country and one in the US published about the same time. One had a 95% certainty that it did and the other a 98 or 99% certainty that it did not! It is important to remember that 95% means 1 in 20 times its wrong and even 99% is wrong 1 out of a hundred. (and sidebar a 14% chance happens 1 in 7 cases on average). Both studies had several thousand subjects which turned out to be too few given all the variables in heart attacks. Ultimately another study was done with a 20-30X more subjects and was felt to clearly show the benefits of aspirin and further studies have gotten us to the low dosage recommendation today.
With that long intro, Covid-19 is challenging from several perspectives. We don’t know most of the factors of why some people get it, and why some people either don’t get it or don’t know they got it. There is now highly certain cure — so you can’t intentionally inflect someone (ethically). The inflection rate while scary is low. So to get a statistically significant result of a truly preventative study you would need a large same. Even a sample of 100,000 people would only result in 500 cases in the US today. So half getting a preventative drug and half a sugar pill. Unless the preventative treatment was massively effective (so well less than half of the expect 250 inflections) to get a statistical defensible result. Again we just don’t know the all the factors and I would bet if you studied two well selected “identical” groups of 100,000 people with no treatment the difference between the number of resulting cases would be 10-30%.
Studying effectiveness in early detected cases is easier since you know the person has been inflected so a study of a few thousand taking a drug to reduce the spread of the infection would be easier to get statistical meaningful results.
These challenges don’t mean we shouldn’t be working really hard to find prevention treatments and early onset treatments. Just because it hard and expensive, the need is clearly there.
We do have to chose our trialed drugs, especially for prevention studies, carefully as even with the seemly unlimited budget of the US, there are practical limits on how many studies.
I think some of the drugs mentioned in the Harvard doctors’ op-ed are good candidates. I suspect (personal opinion) that the required monitoring of people taking HCQ for heart issues (while a low percentage, its still real) would point to other drugs as better starting points.