Friday, May 22, 2020

Don't Ask, Don't Tell

The Jacksonville Lady

Treatment Update:
Famotidine: Yet another prematurely posted research preprint has been making trouble: a study saying the acid-blocker famotidine protected people with COVID-19 against dying or winding up on a ventilator. It’s gotten a lot of press, but several problems leap out at me. First, it’s not a clinical trial but a retrospective look at people who were given the drug in the hospital. Second, we have no idea why these particular patients were given famotidine. And third, the entire analysis rests on the back of a tiny number of patients. If 10 famotidine patients had done poorly instead of 8, the results would no longer be significant.
Heparin: A discouraging report from Austria describes autopsies on 11 patients who died of COVID-19. All of them had blood clots in their lungs, even though 10 of the 11 had been on anticoagulant therapy. This disease does very odd things to blood vessels – including “COVID toes” as well as the Kawasaki-like syndrome in children – that, it seems, can’t be blocked with heparin type drugs.
Convalescent serumA report on more than 5000 patients across the United States says this treatment has been demonstrated to be safe. Demonstrated safe is good; demonstrated effective would be better, but in any case the use of this promising therapy is constantly expanding. N.B. the hard-hit Hasidic community of Greater New York, which has behaved pretty poorly during the epidemic, has been compensating by providing a particularly large number of donors
Hydroxychloroquine (Plaquenil): I wouldn’t have included it this week, because the only news was Mr. Trump’s nightly dose… But no! Hot off the presses! Today the next-to-last nail was hammered into the coffin of hydroxychloroquine for, with the publication of an observational study of 96,000 COVID-19 patients worldwide: those taking hydroxychloroquine had a 34% increased risk of dying, and those taking it in combination with antibiotics 45%. I say only “next-to-last” because a randomized, placebo-controlled Australian trial is still in the works. We also now have some data about the preventative use of hydroxychloroquine, because enterprising researchers have looked at COVID-19 among patients with lupus, many of whom take hydroxychloroquine every day as treatment. Guess what? The ones who were on it developed COVID-19 just as often as those who weren’t, and when they did get COVID-19 they got just as sick. 
But hydroxychloroquine’s unearned fame as a COVID-blaster is a hydra with many heads. A comment about my blog on Facebook taught me it lives on far beyond the right-ring Twittersphere. The reader linked to a video entitled “Another Dr. speaks out on the CV HOAX” (46,278 views in 4 days) and an article called “Fauci knew about HCQ in 2005 -- nobody needed to die.” Some suggest I shouldn’t link to charlatans and hoaxers, but I think it’s better to know the enemy. There’s so much COVID madness out there that I was willing to accept as genuine a video where a proud Jacksonville, Florida denizen opined, “Miami is where y'all got the virus because down there in Miami, you got all them Mexicans and they're drinking all that Corona beer.” So many people were taken in that she had to issue a public statement assuring that the video was satire.
Remdesivir: Oddly, supplies of the only drug with evidence of (modest) activity against COVID-19 are being doled out by the feds in dribs and drabs – the first shipments went to only five states and the distribution to states hospitals is still weirdly uneven. In yet another odd twist, remdesivir may wind up being commercialized in Europe before it is in the United States. 
Artemisia: I’ve mentioned a secret potion from Madagascar that seems to include this antimalarial herb and is being sold all around Africa as a COVID-19 cure. Some researchers in Germany are apparently taking the concoction’s chief ingredient seriously. I’m not.
On beyond drugs: A small but important study in Seattle has provided the most direct evidence to date that physical distancing is effective in preventing COVID-19. The researchers examined swab tests taken from more than 17,000 hospital outpatients over six weeks, and found that the rate of COVID-19 positivity peaked precisely five days after “social distancing” orders were instituted, corresponding to the usual incubation period of the virus, and fell off steadily therafter. More evidence comes from a modelling study from Columbia University epidemiologists, concluding that 55% of the deaths in the United States would have been averted if social distancing had been instituted just one week earlier – in New York City, 80% (17,514 deaths). I don’t think any authorities, however brilliant, could have been prescient enough to close down that early. But you may possibly remember that in an earlier blog post I came down on Governor Cuomo and Mayor De Blasio for not closing down New York City five days earlier, immediately after California had paved the way. 
Vaccines: Moderna’s candidate vaccine has passed a major test: a handful of volunteers – 8 in all – developed neutralizing antibodies against the novel coronavirus after receiving two doses of the vaccine. This can be fairly called a milestone moment, because it is the first time any COVID-19 vaccine has been reported to induce antibody formation in human beings. But it’s a press release, not an actual manuscript, and America-firstism may have pushed Moderna into announcing early. The Oxford vaccine has already been administered to more than 1000 volunteers, but the researchers are waiting before they publish any results. Other candidate vaccines have started human testing in Germany and China.
We now have more information about the macaque monkey studies of that same Oxford vaccine, and it turns out their much-vaunted success is more nuanced. A pre-printed manuscript that contains more data than the previous press releases reports that the coronavirus multiplied in the lungs of 2 out of the 6 vaccinated monkeys, that 3 of the 6 seemed short of breath, and that the virus grew in the noses of all the monkeys, vaccinated or not. Yes, the vaccinated animals became less ill than the controls, and the amount of virus deep in their lungs was less, but these are definitely less brilliant results than we had been promised. I’ve looked back at the similar experiment with a Chinese vaccine, and I think – though I’m not sure – it did better than the Oxford one.

More on those Stanford University studies
Remember that Santa Clara study I’ve been obsessed with, the one that claimed the virus wasn’t so bad after all so we might as well get the economy back up and running? It turns out that study was funded in part by a certain David Neeleman, and he’s a guy who happens to have skin in the game. He has founded five airlines – the first was JetBlue, the latest something called Breeze that he started up in February of this year. So if as the study’s senior author has said on Fox News, the risk COVID-19 poses to most people is “In the range of dying while you're driving from home to work and back,” we all might as well climb back on those planes. The addition of financial conflict of interest to terrible science was the last straw for Stanford, which has now opened an investigation. I hope it will end with a disavowal of this embarrassing study, which I predicted from the start.
Now the Los Angeles study from the same group has been published, and it’s better but still not good. At least they didn’t get their subjects to have their blood tested for COVID-19 antibodies by advertising on Facebook, but rather invited a random sample of the population. Unfortunately only half of those invitees showed up to be tested, which means the subject group was overstuffed with people who presumably wanted to be tested because they thought they had had COVID-19. In fact somewhere between 13% and 38% of the subjects reported having had typical COVID-19 symptoms at some point during the past 2 months, accounting for as many as 70% of subjects who tested positive. So the very high rate of antibodies they found and claimed reflected the rate in all of Los Angeles, 4.65%, is barely more than wishful thinking (if what you’re wishing for is to reopen the economy ASAP).

Lies, damned lies, and statistics
According to Donald Trump, the reason our COVID-19 stats look bad is that we do too many diagnostic tests. “We have more cases than anybody in the world. But why? Because we do more testing. When you test, you have a case. When you test, you find something is wrong with people. If we didn’t do any testing, we would have very few cases.” Great idea! Let’s make like an ostrich and put our heads in the sand, maybe that way people will stop dying.
Pete Ricketts, the Governor of Nebraska, has a cleaner approach: do the tests, just don’t report the results. As cases rise in his state’s meatpacking plants and nursing homes, he has announced his state will no longer report the number of cases related to individual locations.
But the booby prize goes to the state of Georgia, whose Department of Public Health released the following graphshowing how COVID-19 cases in its five worst-hit counties had been trending over the previous 2 weeks:


Those cases were coming down nicely, right? Now put on your specs and look very closely at the x axis. April 27thcomes before April 26th, May 6th before May 3rd… The people who were doctoring this graph to justify Government Kemp’s premature reopening were so stupid that they left the actual dates for us to see, after having switched the columns around! When their bungled attempt to mislead the public was greeted with guffaws and “It's Just Cuckoo” headlines they posted the real graph, which showed no falloff over time. 



Except – apparently – for there being close to zero new cases on the last couple of days. A little snooping, though, told me that’s only because Georgia suffers from a 3-to-10 day lag time between when it sends a specimen to the lab and when it reports the results.
The idiocy of the Trump Administration’s handling of the pandemic has received surprise blowback out of left field. In a truly extraordinary move, The Lancet – a British medical journal that is one of the most prestigious in the world – has published a no-holds-barred editorial blasting the United States government for botching the American response to COVID-19. It focuses on the emasculation of the CDC and the defunding of the World Health Organization, and ends with the even more extraordinary plea to the American people to vote Trump out in November. It is impossible to overstate how unusual this is, and I can’t resist asking: will The New England Journal of Medicine be next?

Full speed ahead
The coronavirus is just starting now to make its much-feared entry into the Third World. In India the official death count (guaranteed an underestimate) is already over 3500 and is expected to rise much higher as the disease spreads in crowded slums and villages; the hospitals in Mumbai are already overwhelmed. Several African countries also have blazing new hot spots. 
In Brazil the epidemic rages out of control, with 1188 deaths yesterday. President Jair Bolsonaro’s reaction is, and I quote: “So what?” (“E daĆ­?”) Back in March, you may remember, Bolsonaro’s chief bodyguard and at least two members of his cabinet came down with the disease.
In Russia COVID-19 is also on the rise, but do you trust them to tell you what their death toll really is?
In Italy we are now much closer to knowing the true toll of the pandemic. We had previously known that the number of deaths from all causes in March had been 24,600 more than would have been expected based on previous years. Now that number has been updated to include April: a total of 46,909 excess deaths. This is a whopping 71% higher than the official COVID-19 death toll of 27,938, and leaves in the dust the modest 25% that epidemiologists have estimated as the usual undercount. Some of those excess deaths will  have been due to people with other diseases, such as heart attacks, dying at home because they were afraid to go to the Emergency Room, but in the disastrous Northern Italy of that period the vast majority were likely COVID-19 victims who died without benefit of a confirmatory test, whether at home, in residential facilities, or in the hospital.
If it is any comfort to Italophiles, those undercount stats are even worse in the United Kingdom.

In the USA, it’s the usual patchwork: things are getting better here, worse there. Above is a county-by-county map – you might enjoy the interactive original at the National Geographic website. The choice of red for increasing and blue for decreasing happens to correspond roughly with politics, since the epidemic is receding in “blue states” along the coasts while it invades the “red states” of the heartland. But with the disease largely growing in prisons, meatpacking plants, and other locations of such “others” as immigrants and African-Americans, the red state governors seem to be mentally echoing Bolsonaro’s “So what?” as they plow ahead with reopening their economies.
If you look cross-eyed at the state-by-state pattern of reopening in the United States you may see a vague resemblance to the National Geographic county-by-county map – the states that are reopening fastest are the very ones where COVID-19 cases are increasing
For even more explicit evidence of the mess Republican states are making of their pandemic response, here’s another great graph, which comes from a terrific article by two CDC veterans:


Mask don’t mask
Dozens of people sent me the link to “The Risks - Know Them - Avoid Them,” a very sensible and practical blog post by Erin Bromage. The writer isn’t as down on masks as I am, but he does comment, "If I am outside, and I walk past someone, remember it is “dose and time” needed for infection. You would have to be in their airstream for 5+ minutes for a chance of infection.” That’s what everybody is concerned about, passing casually on the street or in a store within range of a person who has COVID-19 without knowing it – it’s true that that the disease is maximally contagious during the very first days of clinical COVID-19 and the couple of days before the symptoms start. But given the intensity of exposure that seems to be necessary to get infected, will it make any difference whether that person wears a mask or not? I sincerely doubt it.
A random observation: it’s my impression that the previously well-distanced and well-behaved Berkeleyites, as soon as you put a mask on them, have started mobbing us at the farmers’ market and invading our space on the street. That old false sense of security… Totally unscientific, coming from a prejudiced observer, and probably wrong.

Department of Tiny Good News 
It looks like spitting in a cup may eventually be at least as good as having a giant Q-tip stuck through your nose for detecting active COVID-19. So far this is not very practicable – testees have to keep spitting and spitting until they collect enough to fill a standard urine cup one-third of the way up. And the test itself has to be done in a lab, so it can’t be ready until the next day. But it’s proof of concept, and eventually I’m pretty sure there will be a truly reliable rapid PCR test, whether using spit or a self-administered nasal swab, that could be used to screen people as they enter a restaurant, a concert, or a sporting event.
Another option for the same purpose might be a rapid antigen test, like the throat swab for strep I use all the time in my office. We’ll see how that one works out.
This rapid-test stuff is exciting, but it’s important not to jump the gun. Case in point: it turns out that the test Donald Trump was being reassured by every day, produced by the reputable firm Abbott, may miss as many as a third of COVID-19 cases. Abbott is fighting back against the critics, saying their tests were used wrong, taken wrong, transported wrong, whatever, but fact that the lousy stats came out of high-level medical institutions such as NYU Langone and The Cleveland Clinic makes both the company and its tests look bad.

Unwelcome to my inbasket 
From Medicare.gov, with the subject “Look out for COVID-19 scams.”
·       Robocalls offering you respiratory masks they'll never send
·       Social media posts fraudulently seeking donations for non-existent charities, or claiming to give you stimulus funds if you enter your bank account information
·       Fake testing kits, cures, "immunity" pills, and offers for protective equipment
From balto212@gmail.com, with the subject “Go fuck yourself you fucking piece of shit fake news SNOW FLAKE baby killer cock sucker libhole motherfucker. MAGA.” The body of the email was empty. I take this to mean Stethoscope has hit the big time. Unsurprisingly, I’m not the only person to have had the pleasure of hearing from this gentleman. One of the others commented: “Do you think he was expressing how much he enjoys my writing? Probably not, but I'd suggest he quit reading it before he suffers a seizure.” 

Reopening update
-       In Italy as of this week you can knock back an espresso at the bar! Have your hair cut! Even step outside your front door without a permit!!!
-       You can go into restaurants and pubs too, and in the first couple of evenings social distancing was such a mirage that mayors around the country threatened to seal off their nightlife neighborhoods. They’ve fined few bars, though, and even fewer individuals. According to my informants the locals are behaving well in downtown Rome but there’s some cheek-to-jowl socializing in less central neighborhoods.
-       The Germans stuck to their guns and rebooted professional soccer despite having players out sick with COVID-19.
-       And Travis McCready pulled off his concert, though a few days late and in a different venue.
-       Around the world museums are starting to reopen, usually with prebooking, one-way itineraries, and limited entry. In Rome you can visit the Villa Borghese but not the Vatican, in Naples the Museo Madre but not the Archaeological Museum, in Paris the Giacometti but not much else. In Berlin the vast majority have reopened, in London none at all. Eight American states are letting the public back in their museums, but in New York City the prospects are so bad that institutions from the Metropolitan Museum to the Museum of Modern Art have been laying off staff; reopen pleas even from small upstate museums have fallen on deaf ears. 
-       Turns out the the CDC’s roadmap for reopening wasn’t actually tossed in the trash, as I thought last week, merely put on the shelf. Now both a set of checklists and a fuller version have been released, though the former is highly succinct and the latter contains more legalese than straight talk… But remember what I said about those evangelical votes? The main omission from the original draft is the entire section of thoughtful guidelines that had been drawn up for places of worship, which covered everything from shared prayer books to choir rehearsals.


Alitalia rides again
Remember the nonstop Alitalia flight my husband and I were taking from San Francisco to Rome on June 1st? Ten days ago someone named NOREPLY notified us the flight had been cancelled. Stranded again. The airlines also zapped the last remaining direct flight to Italy from anywhere in the United States, Alitalia’s daily run between JFK and FCO, and all the few remaining nonstop flights from San Francisco to anywhere in Europe. Several are promised in June, but an inside informant has suggested we not trust any of them to come through. Faced with the choice between staying on in Berkeley indefinitely, saying a Micawberesque “Something will come up,” or taking a horrific but guaranteed journey home via Los Angeles and Paris on Air France, three planes and four airports, we chose the latter. Our ticket is for May 30th – wish us luck!