Thank You, Omicron!

A movie poster, Photoshopped as a goof and billed as "a 1963 Italian movie" 

Major updates on Omicron, mitigation measures, and Italy, some important booster news, and detours for Trump, animals, and COVID foolishness.

 

Treatment updates

Lenzilumab: In a large, randomized, placebo-controlled Phase 3 trial among hospitalized patients, this antibody against a pro-inflammatory cytokine (granulocyte-macrophage colony-stimulating factor) cut the percentage who wound up dead or on ventilators from 22% to 16%, without significant side effects. The results suggest it may be more effective than its competitor tocilizumab (Actrema), which received emergency authorization from the European Medicines Agency a few days ago.

Molnupiravir: Oxford University is plowing forward with a large-scale UK study of the Merck pill I fear is both risky and ineffective. Headlines still bill it as “game-changing.” A European Medicines Agency report has cautiously concluded only that the drug “might provide clinical benefit” in certain patients, and the FDA is still stalling, but countries are already snapping up doses.

Paxlovid: Pfizer’s anti-COVID-19 pill came under EMA review on November 19^th, and final trial data are on their way to the FDA as we speak. Merck, not surprisingly, is gunning for it.

Monoclonals, meet Omicron: Bad news: after studying Omicron's individual mutations, Regeneron believes its Regen-Cov monoclonal antibody product will be substantially less effective against Omicron than against earlier variants. Good news: based on laboratory testing and studies in hamsters the makers of sotrovimab – already our most effective monoclonal antibody treatment – think it will work fine against Omicron.

 

Vaccine updates

Pfizer wanes: Yet another study of the effectiveness of the Pfizer vaccine over time, this one from Qatar and pretty depressing. Protection fell to only 52% against all SARS-CoV-2 infection 4 months after the second dose, and to around 20% by 5 months. Against symptomatic COVID-19 the effectiveness peaked at only 82%, considerably lower than in other studies, and it fell close to nil by 5 months after dose 2. The vaccine did, however, remain more than 90% effective against severe or fatal disease for 7 months.

Novavax rises?: As a BMJ investigator asked this week, Whatever happened to the Novavax vaccine? The company still hasn’t applied to the FDA for emergency use authorization, legal trouble has sent its stock values plummeting, and it has had manufacturing issues ranging from trouble scaling up production to serious quality control problems. But the European Medicines Agency hopes to authorize it soon (Messaggero headline: “Novavax arrives in January”), perhaps for use only as a booster.

Boosters in the lab: A British study has compared immune responses to a variety of vaccines tested as possible boosters after AstraZeneca and Pfizer. The results are kind of confusing, but I do understand that mixing and matching was better than repeating the same vaccine, mRNA third doses boosted neutralizing antibodies against the Delta variant, Moderna was better than Pfizer, and both were considerably better than Novavax. Limitations: the third dose was given only 10-12 weeks after the second, the Moderna booster was full (100 mg) rather than half dose, and immune responses in the laboratory don’t necessarily predict real-world effectiveness.

Boosters in real life: But now we do have a randomized, placebo-controlled study that Pfizer performed in some of its original Phase 1/2/3 trial volunteers, and it confirms the Israeli findings of boostering back to 90%-plus efficacy. According to a Powerpoint presentation, protection began rising after 7 days and increased gradually over 10 weeks. Nearly as important is that none of the 123 cases in the unboosted placebo group were severe enough to require hospitalization, showing once again that the vaccine continues to protect against severe disease, even at an average of 10 months after the second dose. Pfizer doesn’t specify the calendar dates the boosters were given, but given the timing of the original trial this study was probably completed before Delta hit, which limits its relevance considerably.

Post-vaccine myocarditis: A report from Israel emphasizes that the risk of myocarditis in young men is slightly more following infection with SARS-CoV-2 (12 excess cases per 100,000) than it is following vaccination (9 excess cases). The authors seem to be think these results bolster the safety of vaccines. I’m not so sure. Everybody gets (or should get) vaccinated and are therefore at risk for post-vaccine myocarditis, whereas only a small minority would ever be infected and therefore at risk for COVID-19-related myocarditis. So I do not find this brief report reassuring, quite the contrary.

 

Covering the world

Countries with Omicron cases, December 10th

This map of Omicron’s global spread as of December 9^th shows the futility of the travel bans slapped on South Africa within 24 hours of its announcing the new variant on November 24^th. And if the map weren’t enough, we now know that there were already cases in Scotland on November 20^th, in the Netherlands around the 17^th, and in the United States as far back as the 15^th!

As predicted, the multi-mutated variant excels immune evasion, often infecting people who already have antibodies from vaccination or a previous bout of COVID-19. But vaccine protection could likely be restored by booster shots, according to the laboratory study described in a Pfizer press release. Neutralizing antibodies against Omicron were almost absent in merely double-vaccinated individuals, but one month after a third dose they had soared to levels expected to be highly protective. The proof of the pudding is in the eating, though, and it remains to be demonstrated that the boosters work as well against Omicron in the real world as they do in the laboratory. 

Incidentally, both antigen rapid tests and molecular PCR tests seem to pick up Omicron as well as they do any other variant. And, also incidentally, I see absolutely no scientific basis for the Pfizer CEO’s self-interested prediction of imminent need for a 4^th shot.

Did any Greek scholars among you notice that the World Health Organization skipped both Nu and Xi when it called the new variant Omicron? They say it’s because Nu could be confused with new – and there I was, looking forward to a Yiddish variant! – and that Xi could offend people with that name, including Chinese leader Xi Jinping.

 

All hail Omicron!

The Omicron variant has brought an early Christmas present to England. Back in July Boris Johnson tossed all COVID-19 restrictions in the trash, when cases were already spiking so any reasonable person would have tightenedthe rules. The result has been an unstoppable surge in cases, and a doubling of the number of COVID-19 patients in hospitals. But now along comes Omicron, providing a perfect excuse for the “Plan B” that should have been put into place months ago: masking, initially just in shops and public transport but later also in movie theaters and concert venues; a new Green Pass, though only to get into nightclubs; PCR tests and brief self-isolation for everybody entering the UK; and recommendations to work from home. Johnson even tossed out a tiny trial balloon about vaccine mandates, while others already contemplate a Plan C. South Africa will be a convenient fall guy to blame for economic consequences. 

Omicron has also been good to Italy and the USA, offering them an excuse for improved border controls. The stated reason may be Omicron, but the result will be appropriately intensified swab screening, and hopefully even quarantines for travellers from COVID-19 hot spots with whatever variant. And Omicron panic may have been behind a very brief doubling of the number of Americans being vaccinated.

But Omicron may have something even bigger to put under the Christmas tree. If, as speculated, it turns out to be evenmore contagious than Delta, it should succeed in quickly dethroning the latter as the world’s dominant COVID-19 variant – it seems likely to beat out Delta in Denmark and the UK within the next week. Since the new variant seems to cause much milder disease than Delta, the crowning of Omicron could make the entire pandemic evolve for the better: more cases, but fewer hospitalizations and fewer deaths. 

South African reassurances in that sense must be taken with a pinch of salt, because of their motivation to eliminate travel bans. But all 582 known cases in the European Union as of December 10^th were either asymptomatic or mild, only one of the 40 US cases has needed hospitalization, and Zeynep Tufekci’s warnings about Omicron’s dangers for the elderly are thus far merely theoretical. Most cases have been in young people, largely because they’re bigger travelers; within a week or two, when older people have been exposed, we should soon know a whole lot more about severity. Fingers crossed, Omicron may turn out to be not the variant from hell but the variant from heaven. When I first read that idea I thought it was pure fantasy, but I’m not alone in believing now that there may be real cause for optimism.

 

A nudge down the path to extinction?

There are only a few thousand snow leopards left in the wild, meaning the Himalayas and points East. This magnificent big cat was the star of a famous book by Peter Matthiessen and a recent French best-seller by Sylvain Tesson (in English: “The Art of Patience”). Now, sadly, 3 of these endangered animals have died of COVID-19 in a Nebraska zoo. Many species are susceptible, and lions, hyenas, tigers, and gorillas are known to have picked it up from zookeepers. There’s a move now to give vulnerable zoo animals their own vaccine.

Don’t worry about your pets getting you sick, though – cats and dogs can catch COVID-19 from their owners, but it’s a one-way street.

 

 

Beaglegate: Speaking of animals, you may have heard that Anthony Fauci is funding researchers who torture beagles. Those studies really exist, in Tunisia, but Dr. Fauci’s agency has nothing to do with them. The researchers did initially claim NIAID funding, but that was apparently due to honest error and they took it back as soon as the NIAID noticed and protested. Fauci has taken an enormous amount of abuse since the pandemic began, but never as much as over this pseudoscandal – the thousands of callers threatening him with death or torture threats made him stop his assistant from answering the phone for weeks. 

 

Warding it off

The BMJ has published a valuable review and meta-analysis of non-pharmacological measures for combatting COVID-19. After screening 36,000 studies and reading through 650 articles the authors found only 72 that were useable, about half studying individual measures and half multi-intervention packages. Almost all the studies had important flaws, but I think it is nonetheless possible to list the various measures in rough order of their effectiveness:

-       Package interventions combining lockdown, physical distancing, school and workplace closures, and isolation/stay at home measures are strikingly successful;

-       Lockdowns by themselves yield substantial drops in cases and deaths;

-       Isolation/working from home decreases transmission by 50%-75%; 

-       Mask wearing cuts both cases and deaths in half; 

-       Physical distancing decreases cases by 25%

-       Handwashing: cases apparently fall, but all the studies are methodologically weak;

-       Business closures bring a small but significant reduction in transmission rates;

-       Disinfecting surfaces lowered household transmission in a single Chinese study; 

-       School closures: some positive effect in most but not all studies;

-       Border closings: data too scanty to be reliable;

-       Temperature screening: completely useless.

 

Trumping it

Deborah Birx, Donald Trump, Anthony Fauci

In case anybody had doubts that the Trump White House worsened the pandemic by downplaying the dangers posed by COVID-19 and muzzling advisors and scientists, those doubts should be dispelled by documents released by the House Select Subcommittee on the Coronavirus. Emails, and transcripts of interviews with CDC officials and pandemic advisors, make it clear that:

-       CDC officials were forbidden to hold briefings on mask guidance 

-       They were forced to sign off on using the pandemic as an excuse to expel migrants

-       The administration attempted regularly to interfere with the famed Morbidity and Mortality Weekly Reports

-       Director Dr. Robert Redfield intervened personally to block at least one MMWR

-       The administration obliged the CDC to advise against testing asymptomatic people

The titles of a few of the Subcommittee’s reports say it all:

-       Select Subcommittee Releases Data Showing Coronavirus Infections And Deaths Among Meatpacking Workers At Top Five Companies Were Nearly Three Times Higher Than Previous Estimates

-       Select Subcommittee Releases Staff Report Showing Trump Administration Wasted Taxpayer Dollars And Failed America’s Families In Pandemic Food Box Program

-       Select Subcommittee Releases New Findings From Investigation Into Fraudulent Federal Contracts For N95 Masks

-       Chairman Clyburn Releases Memo With New Evidence Of Political Interference In Pandemic Response

All this as the news broke that Trump was almost certainly contagious during the debate with Joe Biden, and that he knowingly exposed more than 500 people before and during the bout with COVID-19 that nearly killed him.

 

Italy update

Checking Green Passes on a Rome bus

The glass is looking more half empty than half full, as COVID-19 cases in Italy keep rising sharply (not deaths, though, thanks to high vaccination rates). That will only worsen if the government remains on its current track.

Some new measures are theoretically cool but unenforceable, such as requiring Green Passes on city buses and subways. Yeah, OK, on day one of that rule nearly a thousand €400 fines were handed out. But that’s typical for Italy. New laws get strictly enforced on day one as a piece of theater, then the number of fines plunges. At least the government has FINALLY set a vaccine mandate for teachers and cops, which is set to kick in on December 20^th.

If only the authorities would aggressively enforce the existing Green Pass requirements (widely ignored in restaurants and trains), reinstate capacity limits, mandate indoor ventilation, close discotheques, quarantine people coming from surging countries such as Germany and Romania, and bring back meaningful restrictions in the worst-off regions. Calabria is about to join two other small regions in the Yellow category – but virtually all that will mean is a senseless insistence on outdoor masking. Veneto, Lombardy, Emilia Romagna, Marche, and Liguria may also soon go Yellow. But since color criteria are based on the percentages of hospital beds occupied by COVID-19 patients, troubled regions are now madly expanding their bed capacity so the numbers will seem to drop even as ever more patients are desperately ill. 

My pet peeve: nearly every day I hear of sidewalk swab tents set up by pharmacies (as opposed to public drive-in centers) running tests on people with COVID-19 symptoms. That’s strictly forbidden by law, in order to protect personnel and customers, but many nurses don’t ask and many patients lie. 

On the bright side, not only have 88% of Italians 12 and over had at least one shot, with 85% fully vaccinated, but the country administered 620,000 first doses in the month of November, when everybody thought the vaccination campaign had slowed to a crawl. About 240,000 were to teenagers between 12 and 19, the other 380,000 to repentant no-vax adults. And – even better – the number of first doses has been rising week by week: 15,000, 18,000, 19,000, 22,000, 30,000, now 40,000 a day. A major reason is the Super Green Pass effect: as of December 6^th anybody who hasn't recently had COVID-19 can’t enter a sport stadium, a movie theater, or a restaurant unless they’re vaccinated. Unfortunately gyms (very popular here) are still open to anyone with a negative swab, and masks aren’t required during workouts.

The rush on boosters in Italy (400,000 a day, the equivalent of about 2½ million in the US) would be good news if not for the fact that at that rate all the supply of doses will dry up before Christmas. I’d call it a case of biting off more than they can chew: on December 1^st Italy simultaneously lifted all age restrictions and changed the timing from 6 months to 5 months after the last dose. The scramble for more doses is on.

 

No State is entirely useless, it can always serve as a bad example

Black stars (the opposite of gold) on a map of COVID-19 cases per capita

Alabama: A bill from the State Senate, passed in the name of “standing up against tyranny,” lets anyone who wants a religious or medical exemption from federal vaccine mandates have one on their own say-so. 

Kansas: The Republican-dominated legislature came back into special session on November 22^nd to pass a law nullifying vaccine mandates for federal contractors or private companies. The trick? Forbid employers to question religious exemptions. Governor Laura Kelly signed it into law the same day.

Iowa: Same as Kansas, but a month earlier.

Florida: Ron DeSantis has appointed as his new surgeon general one Joseph Ladapo, a physician tailor-made for the job of yes-man to an anti-mask, anti-vaccine, sometime COVID-19 denying Governor. Ladapo prominently features his affiliation with UCLA but that institution has apparently disavowed him, and his boasts of having cared personally for COVID-19 patients seem to be false. One of his first acts after being appointed was to refuse to don a face mask in the office of a state senator who had cancer – “for fun,” he said. Ladapo already made it into this blog last June by signing an anti-vaccine statement. Here’s how I billed him at the time: “Joseph A. Ladapo, from the right-wing COVID-19-denier group, ‘Frontline Doctors.’ Early on he advocated against shutdowns, and a year and 600,000 American deaths later was still complaining about ‘overreaction to the virus.’”

Florida again: The unstoppable Mr. DeSantis has signed a law forbidding private employers to impose vaccine mandates, which forced Disney World to back down.

Florida once more, joined by Oklahoma, Texas, and Utah: As of December 10^th all 4 states actively block school districts from enacting mask mandates. Arizona, Arkansas, Iowa, South Carolina, and Tennessee also tried, but their bans got struck down in court or abandoned.

Oklahoma: Governor Kevin Stitt gave the boot to Major General Michael C. Thompson as head of the Oklahoma National Guard, after Gen. Thompson advised his troops they needed to comply with the military’s COVID-19 vaccine mandate. The very next day Gov. Stitt distributed a new policy making the vaccine optional, and installed as Thompson’s replacement Brig. Gen. Thomas Mancino, who was willing to back him up. That set up a standoffbetween Oklahoma and the Pentagon that could put thousands of Guardsmen’s military careers in jeopardy, with the Pentagon warning guardsmen they’ll soon stop being paid. The battle grinds on.

Texas, Arizona, Arkansas, Iowa, Florida, North Dakota, South Carolina: Not only don’t they have any mask mandates, but they forbid local governments to enact them.

 

Jerk of the month 

A silicone arm demonstrated on Tik Tok by a Russian influencer

The prize goes to a no-vax dentist in Northern Italy who was desperate to score a vaccine certificate so he could get his medical license back. He trooped off to a vaccination site with a silicone arm, supposedly purchased on Amazon, then bared a bit of phony shoulder. That trick apparently works in Russia, but it pulled no wool over the Italian nurse’s eyes. In the end the guy decided that rather than lose his license permanently, he’d take the shot.