Thursday, April 23, 2020

There's One Born Every Minute

An Open It Up protest in Texas

Treatment update
Remdesivir: Some treated COVID-19* patients, part of a clinical trial in Chicago, seem to be doing better than expected. But the results are preliminary, have not undergone peer-review, and do not include any real control group – nor, shockingly, does the broader study they are part of. All the remdesivir trials in China have been halted because – fortunately for the Chinese – they couldn’t find enough patients. But there may be an ulterior motive, because as of April 23 there is very bad news for remdesivir out of China: A randomized study reports zero difference between treated patients and controls in mortality at one month. The study was underpowered and the results preliminary, but certainly what we're seeing is extremely discouraging. Perhaps, as with other antivirals such as Tamiflu and acyclovir, the drug might have worked better if given earlier in the course of disease, but still…
Convalescent serum: In a Chinese case-control study of 325 COVID-19 patients – again, not peer-reviewed but definitely the best research yet – convalescent serum seemed to help critically ill patients to survive. More than 600very sick American COVID-19 patients have already received plasma as part of a huge study, though it may be difficult to draw conclusions without a non-treatment control group. That study is begging potential donors to volunteer, while in Italy similar research projects (with perhaps 100 patients enrolled so far) are still collecting donors on a “Don’t call us, we’ll call you” basis. Another small piece of good news: a single donation is now being used for two or three patients instead of just one.
Heparin: According to descriptions of tissue samples, hot off the presses from OklahomaNew York, and New Orleans, some COVID-19 patients have clots clogging small blood vessels – but only in the lungs, not all over the body as in Disseminated Intravascular Coagulation. These observations suggest perhaps heparin should be tried more widely, in very sick patients, but it ain’t no magic bullet.
Plaquenil: Finally a couple of halfway decent studies. In the first,  one hundred fifty Chinese patients with mild to moderate COVID-19 were randomly assigned to hydroxychloroquine or standard care. Outcomes were identical in the two groups: the virus remained in the nose for the same number of days, blood tests for inflammation didn’t improve, and symptoms resolved no faster. The researchers did some “data dredging,” examining all three measures in 14 subgroups, and found a positive effect on one of their three measures (symptom resolution), in one subgroup (patients who received no other antiviral therapy). Finding a “significant” result in one out of 42 analyses is a rate expected by chance, and the authors appropriately considered their trial to be negative. The second was a case-control study (a weaker design than a randomized trial), not yet peer-reviewed, that examined 368 COVID-19 patients in Veterans Administration hospitals across the US. Those receiving hydroxychloroquine went on to require ventilators at the same rate as those receiving usual care, and died at twice the rate.
Stem cells: A new entry from Israeli company Pluristem consists of placenta-based stem cells designed to rev up the regulatory side of the immune system and tamp down inflammation – a similar target to tocilizumab’s. Studies are still in a very early phase.
Light touch: Non-pharmacological aspects of treatment are turning out to be very important, because COVID-19 doesn’t behave like a “normal” lung infection. Some people who are gasping with near-death levels of oxygen in their blood are nonetheless capable of talking on their cellphones, while others who are barely short of breath are in the morgue 30 minutes later. As the weeks pass and these patterns become clearer, doctors on the front lines have adjusted their treatment approaches by keeping more people off ventilators, repurposing C-PAP machines, and sometimes simply asking patients to keep rolling over.
Vaccines: The notion of hurrying up the process by deliberately exposing vaccinated volunteers to the virus has unfortunately been gaining ground. I say it’s a fine idea – as long as the researchers themselves are the only volunteers.

Now for my main topic: the latest COVID-19 cons and tall tales…
Drinking the Kool-Aid
Across the country this past weekend, angry demonstrators wielding signs saying “Stop the madness! It is just a cold virus!” “Let me work,” “Give me liberty or give me death,” or “Heil Witmer” [sic], and chanting everything from “Freedom now” to “Fire Fauci,” are demanding an end to social distancing and stay-at-home orders. Their positions are both dangerous and, fortunately, unpopular. (Atlantic has just published an excellent piece on the question of reopening, while Asian countries that let up on their containment measures are already experiencing a new wave of cases).
In Italy we would assume demonstrations like this were egged on by the Mafia. In Michigan, Texas, Virginia, Minnesota, Idaho, Kentucky, and the rest, the provocateurs are right-wing extremistsRepublican donorspro-gun activists, and the country’s President
Crowds are the coronavirus’s best friend. Mass meetings of a Korean church led to more than 5000 cases of COVID-19, and probably more than 100 deaths (I thank an anonymous reader for correcting my original inaccurate numbers). The biggest outbreaks in the United States right now are in locales where people are jammed together – a Ohio prison (1828 inmates, 109 staff) and a South Dakota factory (748 employees). Mardi Gras festivities probably killed a thousand New Orleanians. Is it wicked to hope the Great God Corona may have tossed a few lightning boltsinto those milling “Open It Up” mobs?

Hell Out of Bats 
The latest conspiratorial origin story for the COVID-19 pandemic is that bat virus escaped from a virology lab in Wuhan and spread around the world. Scientists consider that theory thoroughly debunked, even though Chinese have been untrustworthy throughout the COVID-19 story: trying to keep the epidemic under wraps, wildly underreporting their death figures, and producing many research studies that are sloppy, withdrawn, or proven incorrect. What really matters, in any case, is not where the pandemic came from but where it’s going.

While scientists worldwide race to find a vaccine against COVID-19 – there were 86 projects underway at last count – some think the whole enterprise is not worth the trouble.
One such school says it’s useless, that by the time a vaccine is developed the virus will have mutated to the point the vaccine won’t work. Or that maybe we’ll have to get a new vaccine every year, like the influenza jab. The New York Times added confusion by titling a recent opinion piece “The Coronavirus Is Mutating. What Does That Mean for a Vaccine?” Contrary to what that headline implies, the true answer is “Not much.” All viruses mutate, the novel coronavirus mutates more slowly than most, and experts don’t expect those mutations to cause trouble.
The other school says it’s unnecessary – we don’t need a vaccine, because convalescent serum and antivirals are going to be truly great. As far as I can tell this school has only one member, distinguished Italian virologist Giulio Tarro. The reality: convalescent serum may be our best bet at the moment, but it’s never been a wonder cure for any disease, and antiviral medications are a terrific idea in theory but in the real world they rarely do much. Tamiflu, the famous antiflu drug, shortens the illness only by a day or two, and only if it’s started very early. As far as I know there is exactly one example of a antiviral that’s brilliantly effective: acyclovir for herpes encephalitis, a brain infection that used to be nearly 100% fatal. But acyclovir only lowers the risk of winding up dead or a vegetable to 30%. My conclusion: Italians, as my husband always says, are dreamers.

Rapid blood tests for COVID-19, purporting to tell you whether you’ve had the virus and are therefore immune, have burst on the scene in Italy, where private hospitals will perform them on anyone who hands over enough cash, and of course in the United States, global epicenter of both COVID-19 and for-profit medicine.
There are two problems with this picture.
One is that the tests suck. They claim to detect 90% of cases, but in reality they are very inaccurate. Most of those unreliable tests come from China, but even the ones made in USA are not so great, at least not yet. Don’t take my word for it, or the word of USA Today – listen to the World Health Organization, which says those tests are not good enough to be used. This may change by a month from now, when more trustworthy companies such as Roche hope to roll out new, more accurate rapid tests.
Even if the tests were highly accurate, though, we still wouldn’t be sure how to interpret them. Are people who test positive immune from future infection? That’s the hope, but five months after the bug appeared on the scene we still don’t know for sure. Again, we may be closer to the answer a month from now, when studies by Beaumont Health and others, involving screening of high-risk health care workers, ought to show whether those with antibodies to the coronavirus in their blood can get reinfected.
The rapid tests, like a home pregnancy test, give a yes-or-no answer in minutes and are easy and relatively cheap. It is important not to confuse them with the quantitative laboratory-based tests, using an ELISA methodology, that are being used in the most important research studies and to determine which COVID-19 survivors have the wealth of antibodies in their blood that will make them good donors of convalescent plasma. Those lab-based tests require specialized equipment, take hours, and are very accurate.
Conclusion: don’t be the first on your block to get a COVID-19 blood test.

The Thermometer Brigade
In many COVID-19 conversations, temperature is a star. Passengers entering planes, hospitals, and the United States of America have no-touch thermometers pointed at their foreheads, and Amazon aims long-distance thermal cameras at its employees. Many believe screening for fever – in schools, theaters, restaurants – should be a major tool in the new-normal life we all so fervently await. But while fever is one of the most common symptoms of COVID-19, it’s by no means universal. As many as half of hospitalized COVID-19 patients in China and the US had no fever on admission, and patients with milder or asymptomatic infections are even less likely to have fever. It’s foolish to rely on mass temperature screening as our way to detect infection.

Soapy vegetables
Lots of folks are spending their days washing their spinach in soapy water (yecch) and scrubbing their squash with Purell or Amuchina (double yecch). This is absurd. You can’t get sick by ingesting coronavirus, and the virus is killed by cooking.
Disinfecting shopping bags? Leaving your shoes outside the door? Consumer Reports, other experts, and still other experts say don’t go overboard! Do wear disposable gloves when you shop, do patronize only stores that are fussy about social distancing and disinfect their carts, do do your damnedest to keep six feet away from other customers. When you get home do wash to Happy Birthday x2 before and after you unpack the groceries, and do wash any surface you’ve set your shopping bag on. If you’re a fearful sort you can leave packages unopened for a few hours, but there has not been a single case reported of someone getting COVID-19 from handling a box of food or a delivered package. Likewise you may want to leave your shoes at the door once you start thinking hard about what their undersides may have picked up; one of the times I wash my own hands is after changing from shoes into slippers. But the only evidencethat the novel coronavirus can be found on soles comes from COVID-19 wards in China, not from your local sidewalk or your supermarket.

The W.H.O. bogeyman
Donald Trump had a spike in popularity for a couple of weeks last month, pulling the wool over many eyes about his handling of the coronavirus crisis, but as the deaths rise and the pandemic spreads into the small towns of America’s heartland his ratings have fallen again. So he needed a new shiny object to distract people’s attention. What he fixed onwas the World Health Organization – arguably the entity that did the most, the earliest, and the most consistently to draw attention to the pandemic threat. Yes, the WHO made mistakes, especially by taking China too much at its word during December and early January, but it more than made up for them by immediately supporting the January 23 Wuhan lockdown, declaring a world health emergency a week later, and sounding dire warnings nearly every day since. If the Trump administration had acted on those warnings by following the WHO’s recommendations for testing and social distancing, tens of thousands of American lives might have been saved. Trump’s decision to cut off funding to the WHO is scandalous.

Let me wade into the mask controversy with a minority view. The CDC now suggests people wear face coverings when outside their homes, the State of New York wants people to be masked where social distancing “would be impossible,” and as of April 22nd California won’t let you into a store without one. The idea is not that a healthy person will be protected by wearing a mask him/herself, but that people who are infected without knowing it are less likely to infect others if they’re wearing a mask. 
The rationale: some (not all) of the countries that kept the pandemic under control put masks on their population; masks seem to help against influenza; and several studies using machines to generate particles say that masks do a good job of containing them. Also, until not long ago the CDC was urging people to refrain from wearing surgical masks largely so health care workers wouldn’t run out. In a backhanded way, this suggested to the rest of us that the things actually do work.
I used to think masks might be somewhat helpful to keep sick people from spreading the disease. What changed my mind was tracking down the only study to study the question by having actual COVID-19 patients deliberately and systematically cough out infected material. Neither surgical masks nor cloth masks substantially decreased the amount of coronavirus that arrived on a petri dish 20 cm away. Incidentally, for both types of mask much more live virus was found on the outside surface of the mask than on the inside. These researchers did not test the N95 (FFP2 or FFP3) respirator masks, the ones worn by health care workers that are thought to protect the wearer.
Being an open-minded scientific sort, I will charitably mention a study that does not support my position, which analyzed data collected five years ago in Hong Kong. The researchers found some blocking effect of surgical masks on viruses, including coronaviruses, that were causing common cold symptoms. Their methods are not entirely clear, but it seems they somehow collected air exhaled by sick patients while they breathed, and coughed, for 30 minutes. In my opinion this is not very relevant to whether masks will keep asymptomatic COVID-19 patients from infecting people they pass on streets and in store aisles.
At last call the World Health Organization seems to weigh in on my side.
Some are convinced mask-wearing will help psychologically and will encourage healthy behavior. I think the exact opposite: masks will bring a false sense of security, making people less likely to practice proper social distancing, just as many gay men started having unprotected anal sex again as soon as the first mediocre AIDS treatments came out. When one store forced me to wear a mask, even I felt safer – despite knowing better than anybody that it was giving me no protection whatever. While we wait for further research to settle the question, listen to The New York Times: "“This is just the next step,” said a retired corrections officer, Stanley Woo, 63, sitting down to play chess in a park in Forest Hills, Queens, with his old friends and his new mask."
Chess in Forest Hills. Look like six feet to you?

*You may have noticed I’ve switched from “covid-19” to “COVID-19.” It’s an acronym – C for corona, VI for virus, D for disease – so it really ought to be all-caps, like USA.


  1. Nice post Susan... Seems like Remdesivir got a poke in the eye today from a leak regarding a Chinese study. The whole thing seemed hardly conclusive. The U Chicago information was more promising but I guess you can't root for an outcome , we'll have to wait until a peer reviewed conclusion is brought forth.

    1. I heard about that Chinese study on Fox News tonite but didn't change my post having not seen the original report (which is still not available). I don't root for any drugs, just hope for all of them. The statnews screenshot doesn't give much detail, except that the patients were all hospitalized. Maybe remdesivir - as with olseltamivir and other antivirals - needs to be given much earlier. Or maybe it just doesn't work period, too bad.

    2. Today I decided to add mention of that Chinese study to this post. What a damn shame. Here's all you can see about it...

  2. Thank you for posting these updates. As an American (happily) living in Italy I am interested in your perspective and clear view.

  3. excellent as usual
    in case you did not see this, have a look:

    1. Thanks, doc. Wow! I had never heard of Tarro before he came out with this outrageous nonsense about covid-19, but that article confirms that he's a longtime weirdo, cheat, and scammer. I've tried to find something similar in English, without success.

  4. reportedly antisemitism is on the rise as the Jews are being blamed for Covid - go figure.

    1. I hadn't heard THAT one, but now looking it up I see maybe true. The world is nuts.

  5. A small correction to your post - "Crowds are the coronavirus’s best friend. Mass meetings of a Korean church led to more than 5000 deaths from COVID-19." The church meeting led to 5000 cases, not deaths. S. Korea has experienced an extremely low mortality rate, fewer than 300 have died.

    1. Whoops - how sloppy of me! I'll correct the text now.