Monday, September 27, 2021

Booster Boosters, Booster Bashers

 From a spin on the booster roller-coaster to a gallop through triage-land, with detours for masks, monikers, mandates, myocarditis, and mutts.


Treatment news

Bamlanivimab/etesevimab: Lilly’s monoclonal antibody cocktail, with Regeneron’s, is now FDA-authorized for preventive use in high-risk individuals exposed to COVID-19. 

Regen-Cov: A rightwing political activist named Laura Loomer came down with COVID-19 recently and immediately got dosed with azithromycin, hydroxychloroquine, the OrthoMune dietary supplement, and . . . Regen-Cov. Since Loomer is 28 years old I guess she must have diabetes, nonfunctional kidneys, or an immunosuppressive condition, otherwise a young, thin person is ineligible for monoclonal antibody treatment, even in Florida. (…ummm…maybe the rules are different if you have friends in high places…?) Note that the World Health Organization has finally given Regeneron its imprimatur.

The Regen-Cov study of preventing COVID-19 in household contacts has now been properly published. Notably, when the treatment failed and the contact did become infected, symptoms were milder and briefer than in placebo subjects.

Monoclonal antibodies: The American rightwing crowd that hates everything anti-COVID-19 is embracing antibody products. Better than nothing, and may make a dent in the horrific death toll. But protection from passive antibodies is partial and short-acting, so it’s no substitute for vaccination (which antibody-treated patients can get 3 months later). 

Colchicine: Two new studies among high-risk outpatients: it cuts severe outcomes by 25% but does not seem to shorten disease.

Remdesivir: Bad news. The pan-European DisCoVeRy trial, which had already flunked hydroxychloroquine and other drugs, has now published its remdesivir arm, where COVID-19 inpatients on oxygen were randomized to receive remdesivir or standard care. At two weeks there was absolutely no difference between the groups in clinical status or viral load. More evidence the WHO was right to turn thumbs down last November. 

Ivermectin: Bet you’re sick of reading about it. I am. But in case you aren’t

Rivaroxaban: Confirming previous studies, this oral anticoagulant failed to reduce disease progression in COVID-19 patients being treated at home,. Anticoagulation definitely has no place in the treatment of COVID-19 outpatients.

Anakinra: This immune modulator was tested in 405 severely ill COVID-19 inpatients. They were one-third as likely to get worse, and half as likely to die. Sounds great, but I doubt this single open-label study is going to change clinical practice yet.


Vaccine news

Inside a Sputnik V factory

Pfizer: Post-vaccine myocarditis may be more of an issue than we’d hoped. FDA data suggest that it develops, usually after dose 2, in as many as one in 6000 boys between 12 and 15 and one in in 5000-11,000 at age 16-17, with COVID-19 survivors even more at risk (girls get off nearly scott-free). Almost all cases needed to be hospitalized, more than were hospitalized for COVID-19 itself over 4 months. The authors suggest, reasonably, that consideration be given to foregoing vaccination in young COVID-19 survivors, and perhaps giving only a single dose to teenage boys.

Sputnik: The World Health Organization has been contemplating the Russian vaccine since February, but after a factory inspection turned up “possible cross contamination and insufficient sterilization checks” it’s turned thumbs down, at least for now, leading Vladimir Putin to boycott the yearly UN meeting in New York.

Novavax: The published study confirms 86% efficacy, but was performed before Delta hit so is not extremely relevant today, even as evidence piles up that Delta is not just more infectious but more virulent.

Moderna: Excellent efficacy (93%) in their latest article. Pre-Delta, again, but we already know that Moderna shines in the variant arena.


On the booster roller-coaster

Can it have been only on August 18th that President Biden jumped the gun on his own regulatory agencies by announcing – as a centerpiece of his anti-COVID-19 plan – Pfizer boosters all around in late September? It feels like years rather than weeks, given all the ups, downs, and mess. As one Yale professor said just as the boosters started rolling out, “It’s just really, really, really confused, more than I think anyone could have expected.”

Not even the most straightforward facts get reported right. Take a September 15th Washington Post piece: “Some studies have suggested the vaccine’s efficacy declines over time against symptomatic infections, but some have not.” Some have not? None that I can find. All available data, from Israel, England, Scotland, and the US, show the efficacy of the Pfizer vaccine against clinical COVID-19 to fall over 6 months from around 95% to around 60%. 

From the same piece: “The new Israeli information, which will be presented at the committee meeting, is likely to bolster previous data showing that protection from the vaccine, including from severe illnesses and hospitalizations, wanes.” Not true. In Israel the protection from severe disease faded hardly at all, from 91% to 86%. In the UK, similarly, after 5 months the Pfizer vaccine still protected 95% against hospitalization overall, 92% in people over 65, and 68% in people over 80. The only study to find a clear drop was one in the United States, which estimated Pfizer’s protection against hospitalization at only 80% in the Delta era (Moderna’s was still 95%).

Even the New York Times adds confusion, misrepresenting the FDA position on who counts as at high risk of severe COVID-19 by saying “the immunocompromised” when in reality a much broader range of comorbidities, from hypertension to obesity, are included in that category.

Various factors further muddy the waters. One, as I’ve said, is that the moment when immunity seems to wane coincides with the coming of the Delta variation, which is more resistant to all vaccines. So we can’t tell whether to blame the lower levels of protection over the summer on falling immunity or on Delta. 

The other is that all those countries vaccinated by age group, so people vaccinated in January/February were mostly old folks, with weaker immune systems that might make vaccine protection wear off sooner, so it’s not clear we can generalize to younger people. Younger healthcare workers were also vaccinated early, however, and one study from the University of San Diego did find a striking increase in breakthrough infections among them between June and July, though none were severe. But that doesn’t necessarily mean the vaccines were wearing off: on June 15th, California basically scrapped mask mandates, distancing rules, and capacity limits, so those workers were, like everybody else, at increased risk of exposure in their daily lives.

The original Biden plan called for boosters 8 months after dose 2. Then it was 6 months after dose 2. Then the heads of the CDC and the FDA started raising timid doubts… until on September 13th, two top FDA vaccine experts first quit, then signed an opinion piece in The Lancet arguing forcefully against any boosters in favor of prioritizing global vaccine equity. On September 17th, we finally heard from an FDA expert advisory panel: no universal boosters but third doses for the elderly, the sick, and those at high risk of frequent exposure. On the 22nd, the FDA said yes and updated Pfizer’s authorization accordingly.

But the next day a different set of experts in a CDC advisory panel came up with a different set of recommendations: boosters for Pfizer vaccinees age 65 and over or 50-64 with underlying conditions predisposing them to severe disease. Younger high-risk people might be eligible on an individualized basis. Just jours later the CDC chief Rochelle Walensky overruled her own panel, a highly unusual move, reverting to the FDA’s stance by making people with high occupational (e.g. healthcare workers) or institutional (e.g. prison inmates) risk of exposure eligible for a booster. …only to run up 24 hours later, with states already rolling out booster programs, against President Biden reinterating his intention for all Americans to get booster shots. 

In the real world, it’s going to be a free-for-all. People officially get to self-certify as high-risk rather than needing a doctor’s note – an absurd, scandalous honor system. And there’s an even simpler way to get a booster: pharmacies hand out “first” doses without checking for previous ones, leaving the back door wide open for anyone who wants a third dose – and many young and healthy individuals are already coming in that door. With vaccine supplies limited and all those queue-jumpers, people who really need boosters may wind up having a hard time getting them. 

Let’s take a step back to review the evidence in favor of. Much of it comes from limited laboratory studies. As part of Pfizer’s principal Phase 1-2-3 multinational trial, 23 volunteers were given a third dose after 8 months. Their neutralizing antibodies bounded back higher than baseline, with some against the Delta variant. Moderna gave a half strength booster to 344 subjects, sending neutralizing antibody levels sky-high including against Delta – that 50 µg dosage means the same amount of vaccine could boost twice as many people.

But the best support for Pfizer boosters comes from Israel, which is already administering them. Among people over 60, rates of both infection and severe COVID-19 have dropped low enough after that third shot to match the 95% efficacy seen in Phase 3 trials. Some skeptics think the boost might only last a few months, I don’t see why.

Prominent physicians are all over the map. One, Eric Topol, is so pro-booster that he recommended conniving with your local pharmacy to get one by falsifying your medical history. The ever-prudent Anthony Fauci says only that the FDA panel’s rejection of boosters-all-around is “not the end of the story.” Others come down on the anti-booster side, on grounds that the original series still works against hospitalization: “I don’t care about symptomatic disease – I care about severe disease,” or “What [the vaccine] is supposed to do is protect against severe, critical illness.” The New York Times has weighed in on the anti-booster side.

I guess it depends on your point of view. Me personally, I’d rather not get any COVID-19, even the less serious forms which still leave one in 3 patients with long-haul symptoms. My own protection against that kind of “mild-moderate” illness, as an older person 7 months after my second Pfizer shot, is now below 60%. I want a booster. 

Several other industrialized nations are plowing ahead with boosters. Israel is offering one to all comers. The UK will give a full-dose Pfizer or half-dose Moderna third shot after 6 months to people who are over 50, chronically ill, work in healthcare, or live with someone who’s immunosuppressed. A number of European Union countries will follow suit – Italy’s starting with the immunosuppressed, then front-line health workers, then octogenarians.

GermanyAustria, and some places in California are offering a dose of Pfizer to everyone previously vaccinated with Johnson & Johnson or AstraZeneca. I’ve been advocating this for some time now, and hope Italy will follow their example. Anthony Fauci seems instead to be promoting Johnson & Johnson’s dream, a second dose of their original vaccine, an approach backed up by as-yet unpublished data. FDA and CDC decisions about J&J and Moderna should arrive within weeks.

Given the evidence of ebbing vaccine effectiveness at all ages, the argument against universal boosters is more ethical than medical. The WHO keeps pointing out that it’s morally questionable to aim at restoring full immunity to early vaccinees when few in the developing world have had even one shot, urging wealthier nations to donate all their spare doses to poorer ones. So far, nobody’s buying. Vaccinating the world is also of some selfish interest to the industrialized countries themselves, since the most troublesome variants have arisen in poor ones with raging outbreaks (Beta in South Africa, Gamma in Brazil, Delta in India).


K-9s etc.

Airport workers lining up to have their masks sniffed

A few people have asked me whatever happened to COVID-19-detecting dogs. Well, two of them have been hired at Miami International Airport to screen employees – and, eventually, travelers. In addition to direct effects, the roving pooches may discourage people from trying to sneak in by lying about exposures or symptoms on their screening questionnaires.

Cobra, in the picture, is a purebred Belgian Malinois – but other noses-in-training are on mutts rescued from the pound.

When I first reported on COVID hounds I was skeptical that they could be as accurate in the real world as they were in a laboratory setting. But Pokaa, a golden retriever scanning residents at a French nursing home, beats out the PCR test, detecting infections (amazingly) as much as 48 hours earlier. That’s still one-on-one screening, though. It remains to be seen whether dogs can pick infected individuals out of the crowd in, say, an airport.

Speaking of PCR tests, what is wrong with the USA, anyway? I heard on the radio that they’re still hard to get. A New York university website confirms: “In general results are available within 72 hours,” a Washington State health facilitythat “Typical turn-around time for results is 2-3 days. We cannot make any guarantees.” Apparently you can speed things up by finding the right location and shelling out $250-$350. Even antigen tests seem to cost $36-$180 without insurance. In Italy all testing for medical reasons is free; for travel etc. antigen tests cost €15 ($17.50) if you’re on the National Health Service, €22 if you’re not. They’re performed on every street corner and give results, complete with Green Pass, in 15 minutes. A PCR test for travel will set you back €60 ($71) at a private lab, results guaranteed in 24 hours – or even in 4, for an extra fee.


Masks and minutes

I haven’t reviewed the underlying science so I can’t totally vouch for the accuracy of this cool chart, but its creator Asit K Mishra seems serious, the numbers are plausible, and recent research in Bangladesh has shown that even a modest increase in mask-wearing can reduce symptomatic infection. The chart has convinced me to start wearing a KN95 instead of a cloth mask for indoor public spaces. Mask up!


A vaccine by any other name…

Pfizer’s biggest problem in marketing their COVID-19 vaccine could be the ridiculous brand name they’ve picked: “Comirnaty” (accent on the second syllable). It’s meant to be a clever combination of covid, immunity, RNA, and community, but a better descriptor is “objectively hilarious.” AstraZeneca’s “Vaxzevria” isn’t much better, nor are any of the names Johnson & Johnson is said to be considering: Rezymnav, Rezymden, Fampelsen, Aqcovsen, Evcoyan, Abfivden, Jcovden, Ovcinden and Jcovav. They should all hire whoever came up with Moderna’s brilliant “Spikevax.”


Vaccine mandates

Poll: are you in favor of making the COVID-19 vaccine obligatory for everybody?

Italian Prime Minister Mario Draghi has declared it’s planning to make COVID-19 vaccines mandatory for everyone over 12, joining Turkmenistan, Indonesia, and Micronesia (!). Everybody in the broad-based coalition that makes up the Italian government supports the idea except the League’s Matteo Salvini (the frankly fascist Georgia Meloni also disapproves, but she’s not in the government). I surprisingly discovered my inner libertarian and pronounced myself contrary, finding the Green Pass a strong enough incentive – it obliges novax non-healthcare workers to test 3 times a week, on their own nickel.

The astonishing poll illustrated in the screenshot found that a solid majority of Italians, nearly across the political spectrum, favor making the covid-19 vaccine obligatory for all (favorevole = in favor, contrario = against, non saprei = not sure; PD = Democratic party, Lega = League, M5S = Five-Star). Even the fascists in FdI, Brothers of Italy, stand at 48%. The League’s leader, Salvini, still says he'd vote against such a mandate, but 70% of his own voters disagree. Amazingly, only 23% are with me. I might eventually come around to the mandate, though, on the grounds that your right to swing your arm ends at my nose. 

…but days after Draghi’s initial announcement it became clear that the universal vaccine mandate was not a plan but a threat, to be put into action only if 90% of over-12 Italians weren’t fully vaccinated by the end of October; as of September 20th 77% were. At the snail’s pace vaccination is proceeding lately, that 90% seems unlikely.

The idea of compulsory vaccination is spreading in the United States as well. Vaccination will be required for all workers at hospitals that take Medicare or Medicaid funding, as virtually all do (nursing homes, VA hospitals, and the military are already mandated). So will Head Start teachers, federal employees, and federal contractors. As Leana Wensays, Biden could have added anybody crossing state lines in a train or airplane – now you don’t even need a negative swab – and schoolchildren 12 and up (as Los Angeles has pioneered).  Unfortunately a vaccine mandate for New York City school staff is facing resistance in the courts. But I think Biden was wrong not to exempt recent COVID-19 survivors from his vaccination requirements. 

Separately, the Occupational Safety and Health Administration will require workers at all large companies to either get vaccinated or submit to weekly testing – billed disingenuously by many Republicans as a vaccine mandate. Many large companies already demand vaccination – though some, such as Walmart, exclude the frontline store and warehouse workers who are at the highest risk of infection.


Green Pass roulette

In the United States the concept of “vaccine passports” has brought controversy and resentment. In the photo 3 tourists from Texas are punching out the hostess at a popular New York City restaurant who denied entry to part of their partybecause they didn’t have vaccination certificates. The Texans seem to be claiming they were reacting because the hostess called them the N word, which sounds pretty unlikely to me.

New York is now demanding proof of a dose of vaccine to enter a restaurant, a gym, or a public performance. City workers who want to opt out have to get swabbed once a week. In Los Angeles, some establishments have been autonomously carding patrons for weeks now, and the county is about to make it mandatory.

The Italian Green Pass is chiefly intended to encourage vaccination by making life miserable without. The unvaccinated already can’t eat inside a restaurant, see a movie, work out in a gym, or attend a soccer game, and by mid-October they’ll have a hard time working. The powerful Italian unions are fighting a losing battle to get the government to pay for their tri-weekly swabs. Most other European countries use Green Passes, with the odd exceptions of Spain and The Netherlands.

In Italy as in New York City, the right to participate fully in public life starts two weeks after your first dose of any COVID-19 vaccine. Is this reasonable, or should complete vaccination be required? A major, widely publicized studyby Public Health England found effectiveness against Delta after a single dose to be just 36% for Pfizer and 30% for AstraZeneca. But a less well-known Canadian study reported much better one-shot protection: 72% for Moderna, 56% for Pfizer, 67% for AstraZeneca (the only time as far as I know that AstraZeneca has beaten out Pfizer on anymeasure). Splitting the difference, I think the one-dose criterion is reasonable.


Triage hits the big time

As of September 18th, a quarter of US hospitals reported having more than 95% of their intensive care unit spots occupied. Alabama had zero free beds and was reduced to shipping heart attack victims off to neighboring states and equip cafeterias as COVID-19 wards, with 5 other low-vax states close behind. Idaho and now Alaska have formally moved to so-called “crisis standards of care” statewide, postponing life-saving cancer surgeries and offering some desperately ill patients only “comfort care” if the staff judges them unlikely to survive. 

When northern Italian hospitals were having to perform that kind of triage in early 2020, many Americans sneered that it couldn’t happen here. Back then, of course, there was basically nothing you could do to keep from getting sick. Now that there are vaccines some are starting to ask whether people who willfully refuse to protect themselves and others by getting them deserve scarce care. When I touched on the subject on Facebook some days back I found that I’d opened a Pandora’s box of righteous fury:

-       What I don’t understand is why they don’t treat the vaccinated and those needing treatment for other ailments first, leaving the unvaccinated at the lowest rung of the triage totem pole.

-       Voluntarily unvaccinated people with Covid should pay the price of their own stupidity and willful ignorance. Hospitals should send them home untreated, and tell them to "live free AND die!"


No-Vax pride


This gentleman’s home state of Alabama has one of the lowest vaccination rates in the country – and the fullest ICUs. According to my local informant, many Alabamians think the real reason patients die of COVID-19 is because they go to hospitals for treatment!!!