There was lots I wanted to write about, but with so much treatment, vaccine, and variant news, and such urgency to discuss post-pandemic dreams, nothing else would fit.
Treatment and containment news
Ivermectin: A few alert readers may remember my mentioning a year ago that Dr. Paul Sax, a deep-thinking infectious disease specialist, had mysteriously embraced ivermectin as a treatment for COVID-19. Having seen the evidence of data faking, he’s now made an about-face, with apologies. And Andrew Hill, the reputable scientist who published a pro-ivermectin meta-analysis, has published a revised version as, “Ivermectin for COVID-19: Addressing Potential Bias and Medical Fraud.” If anyone still harbored any hopes for ivermectin, a new, huge, randomized, placebo-controlled study should kill them. When given to high-risk outpatients the drug didn’t affect viral load, symptoms, hospitalization rates, or mortality. There’s no persuading the conspiracy theorists, though.
Molnupiravir: Merck’s pill is almost entirely ineffective against the Delta variant, as I pointed out in a Letter I’ve proudly seen published in the New England Journal of Medicine. Laboratory studies say it might do better against Omicron, but they’re mediocre predictors of real-world efficacy.
Paxlovid: I warned in my last post that the few available doses of Pfizer’s miracle COVID-19 pill might go to the influential, the well-educated, and the pushy rather than to the most deserving. In fact, we’re already seeing clinics that serve low-income populations having to turn away a shocking 90% of eligible patients.
Test to Treat: …and that nefarious Paxlovid scenario is now even more likely. In his State of the Union address President Biden showcased a pilot “Test to Treat” initiative that would authorize pharmacists to hand a packet of Paxlovid pills (or, unfortunately, molnupiravir) to a patient at the same time as a positive test result. The plan is brilliant in concept but, in my opinion, profoundly misguided in practice. Two reasons. First, very few doses will be available in the coming months, far fewer than would be needed to treat everybody meeting the criteria, so strict rationing is necessary. Pharmacists are in no position to make those decisions. Second, even with an infinite supply of pills, many otherwise eligible patients shouldn’t take Paxlovid. Pharmacists, and even random physicians, can’t be sure whether the individual has a medical contraindication or is taking one of the scores of medications that risk serious interactions; as a practicing doc I can testify that even well-educated patients often don’t know exactly what drugs they’re on.
Pharmacists are begging that the program be expanded, and pundit Michael Mina thinks it’s the cat’s pyjamas. But the American Medical Association, Eric Topol, and others share my doubts. As the AMA points out, “Leaving prescribing decisions this complex in the hands of people without knowledge of a patient’s medical history is dangerous in practice and precedent.” And a quarter of Americans, skewed toward minorities and the uninsured, don’t have a primary care provider to provide a reliable medical history. So as usual, the white, well off, and well-educated will win out.
Beyond Test to Treat: The rest of Biden’s COVID-19 plan – here’s the detail – sounds great: distribute high-quality masks, improve tracking, study universal vaccines and long COVID, prepare for new variants, avoid lockdowns, and vaccinate both the US and the world. Some experts express quibbles, saying it’s weak on ventilation and health equity. But now it looks like the entire package will go down the drain for lack of funding. What this means, tragically, is that monoclonal antibody treatment will be less and less available, the US will be less able to detect and prepare for new variants, and the 31 million Americans with no health insurance – a number unfortunately soon to rise sharply – will have little access to testing or treatment.
Sotrovimab: Under yesterday sotrovimab was the queen of monoclonal antibodies, the sole Omicron-killer. Its primacy has now been challenged by the peculiar Emergency Use Authorization awarded to bebtelovimab, which I discussed in my last post.
Inhaled corticosteroids: I’ve been prescribing high-dose inhaled steroids for months to COVID-19 outpatients who have either high risk for progression or prominent respiratory symptoms. A new meta-analysis confirms they can both prevent hospitalization and shorten illness, and the authoritative Cochrane Library now calls them also possibly effective for decreasing mortality.
Baricitinib: Following mixed results in hospitalized COVID-19 patients, the latest study says it decreases mortality by 13%.
Face masks again: A study of US mask mandates during 2020 reports they cut infections by as much as 33%, even though at the time the masks nearly everyone was using were the relatively ineffective cloth sort.
Weed: According to the industry website Ganjapreneur, Flora Pharma has approached the Colombian government about testing a cannabis product for preventing and treating COVID-19. The company’s press release seemed a bit coy about the details.
Evusheld: This monoclonal antibody combo, intended to replace vaccines to prevent COVID-19 in immunosuppressed patients, was initially lauded for its efficacy against the Omicron variant. But it turns out that efficacy is less than originally thought, and probably doesn’t last the 6 months initially promised. So the recommended dose has been doubled, and everyone who’s already received a dose has been told to come back for more. There’s also been a striking mismatch between who’s eligible for the drug and who’s getting it, with many doses going unused in the confusion.
|Tobacco leaves drying|
Covifenz: Who expected a new vaccine now? Not me. It’s a two-dose product from the Canadian company Medicago, already approved by Canadian regulators for adults under 65 but probably about to be nixed by the World Health Organization due to ties with Philip Morris. It’s hip for supposed green bona fides – it’s based on “plant-derived, virus-like particles, which resemble the coronavirus behind COVID-19 but don't contain its genetic material.” I was slightly disappointed to learn at canada.ca that the role of plants (tobacco) is only to manufacture the spike protein – from wild strain SARS-CoV-2, which has by now mutated far away. Here’s a description of the process. Overall efficacy was supposedly a respectable 71%, and 75% against Delta, though there’s no proper manuscript yet. Sanofi-GSK: These European pharmaceutical giants’ first vaccine did so poorly at stimulating the immune system of people over 50 that the company didn’t bother to go forward with Phase 3 trials. A new version, which is protein-based like Novavax, did get older people to produce antibodies and memory T cells – but only against the long-gone wild strain of SARS-CoV-2. A Phase 3 trial is said in a press release and announced in the press to show an efficacy of 58% against any COVID-19 and 75% against “moderate-to-severe” disease. If the trial was very recent those numbers aren’t bad, since all vaccines are less effective against Delta and even less against Omicron. The company’s hinted its best use might be as a heterologous booster.
Pfizer: Hearing loss has been reported as a rare complication in Israel, though not in the USA.
Immunosuppression: It’s been debated whether antiinflammatory drugs might interfere with the immune response to COVID-19 vaccination; some physicians advise patients to avoid even aspirin and ibuprofen on the day of and days after each dose. There’s now some concrete evidence that methotrexate (a much more powerful antiinflammatory drug) does in fact interfere with the Sinovac vaccine. Not really relevant to aspirin and ibuprofen…
AstraZeneca: A giant British study confirms that thrombotic complications occur only in people under 70. Oddly, despite having data on tens of millions of people, the researchers didn’t separate out the under-40’s considered at highest risk.
Patents: I thought Moderna had thrown in the sponge in its patent battle against the National Institutes of Health scientists who collaborated on their COVID-19 vaccine, but I was wrong...
Preventing Omicron: A British study has filled in some of the blanks. Two doses of AstraZeneca did nothing much, and boosters faded fast. As usual, Moderna beat Pfizer.
Fourth dose: According to a new study among Israeli health care workers, a second mRNA booster increases antibody levels and (Moderna only) T-cell immunity but gives little real-world protection against Omicron disease (11-30%), and breakthrough infections have a high viral load. The authors conclude, appropriately, that “next-generation vaccines” rather than dose after dose of the same ones are needed to protect against future variants. Who’s pushing a 4th dose? Albert Bourla, Pfizer’s CEO, of course. With Moderna now chiming in. I personally suggesting dose 4 only to people at extremely high risk.
Durable J&J: I’ve mentioned that a laboratory study in a handful of individuals suggested that antibodies faded more slowly with Johnson & Johnson than with Moderna or Pfizer. That’s now been confirmed in a real-world study. A single dose remained effective against both COVID-19 (66%) and hospitalization (72%) for over 6 months, including during Delta. The authors gave even higher rates, but those depend on a statistical adjustment procedure that doesn’t convince me.
Durable mRNA vaccines: One laboratory study has suggested that the antibody boost from a third dose of fades fast, and with it the protection against infection and milder COVID-19, but that memory T cells persist and prevent severe disease. Real-world confirmation: A CDC study found that fully vaccinated American adults were 92% less likely to wind up intubated or dead for 5 months after dose 2, 84% less likely for even more months, and 94% after a booster. That contrasts with much lower protection against mild COVID-19. And for lucky folk with normal immune systems and no chronic medical conditions, even 2 doses gave 98% protection.
Combined immunity: A South African study finds that people vaccinated against COVID-19 with breakthrough Omicron infections emerged with increased protection not just against Omicron, but Delta and Beta as well. But unvaccinated people who contracted Omicron mounted immunity only to Omicron.
Vaccinating survivors: I’m glad to see that Dr. Eric Topol has publically endorsed Italy’s policy of giving a single vaccine dose in people who’ve recovered from COVID-19.
Adolescents: In an American study, 6th to 12th grade students were 9 times as likely to come down with symptomatic COVID-19 if they were unvaccinated. Nothing new there. What is new is that after looking into the sources of infection the researchers concluded that only 2 out of the 27 infections occurred in school. I take this to support my agnosticism about school mask mandates: kids pick up COVID-19 not in the classroom, but at home or hanging with pals.
Gaps: The CDC now recommends that otherwise healthy men and boys between 12 and 39 years old be vaccinated with a 8-week gap between doses, as I’ve long advised for males under 30. An even stricter policy may be advisable for the youngest age group, as per a study of vaccine-induced myocarditis from Hong Kong, showing the highest rate yet reported: one in 2563 boys ages 12-17 following a second Pfizer dose. After Hong Kong joined Norway, Taiwan, and the UK in a one-dose policy for adolescents, there were no new cases. It seems myocarditis may be rarer after a booster than after a second dose, but not by much.
Kids: The efficacy of minidoses of Pfizer in children 5-11 years old seemed too good to be true, and it was. Protection from COVID-19 peaks a week after the second dose but plummets to 12% just 3 weeks later. Effectiveness against hospitalization holds up somewhat better, falling only from 100% to 48%.
Slowing down: In Italy the rate of penitent novaxxers coming in to get a shot has dropped dramatically, from 78,600 a day during the week of January 9th to 3000 a day during the week of March 13th. So have the number of boosters, falling from 537,000 a day to 44,000. But this is likely because people who get COVID-19 are told to wait 3 months before getting any vaccine, and nearly 15% of the entire population has tested positive since Christmas. So vaccinations might pick up again next month.
BA.2: The up-and-coming Omicron subvariant is even more transmissible than the original and is harder to distinguish from Delta on PCR tests, bringing the moniker “stealth variant.” It’s similar to the original Omicron, in its ability to escape vaccine- and infection-induced immunity, and fortunately seems to cause similarly mild disease. BA.2 is now up to 1 in 4 new cases in the US, contributes to the surge England has experienced after stupidly tossing all restrictions in the trash, and is already dominant in South Africa and elsewhere. One laboratory study has suggested that sotrovimab, the Omicron-killing monoclonal antibody, won’t work against BA.2. The manufacturer disagrees, but the manuscript promised in its press release hasn’t come through yet. BA.2 probably does remain susceptible to antiviral drugs.
BA.1.1, BA.2.H78Y and BA.3: Still more Omicron subvariants. I’m unable to find much on them beyond a rather opaque article in Forbes.
Deltacron/Deltamicron: After having supposedly been debunked as laboratory contamination, a variant combining Delta bits with Omicron bits does now seem to exist, though the relation with the original report from Cyprus is unclear. The number of cases it’s known to have caused thus far can be counted on your fingers, and there’s no evidence it’s particularly virulent or transmissible, so why worry?
Post-pandemic antics: USA
…and on March 17th
For once a CDC guideline that’s perfectly clear. Clear – but inaccurate. The CDC web page explaining its new mask recommendations is straightforward: in all counties where “community levels” are low, housing 94% of Americans, nobody needs to wear a mask anywhere unless they have COVID-19-like symptoms, a positive test, or a recent exposure.
As the first 2 maps show, county risk levels went in one day – “like a miracle” as Donald Trump was widely mocked for saying in March 2020 – from almost uniformly high to mostly low-medium. And two weeks later to almost uniformly low!
How did CDC Director Rochelle Walensky make this magic happen? Not with improved prevention or treatment, but by revising her definitions. The wording of the new reigning criterion, “COVID-19 community levels,” looks a lot like the old “levels of community transmission,” but there’s a crucial difference: “community transmission” was based on how many people were getting sick, whereas “community levels” depend on how full local hospitals are.
OK, so that’s clear. Questionable sleight of hand, but clear. So why do I say inaccurate? Because the CDC page fails to mention that masks are still required on interstate trains, buses, and airplanes and in all transportation hubs. This omission is not just ill-considered but risks further fueling the epidemic of “unruly passengers.” Similarly dumb, though perhaps less dangerous, is the failure to specify that patients, staff, and visitors in hospitals and nursing homes are supposed to continue following the old “levels of community transmission” standards, which would currently require masks inside medical settings in the majority of US counties.
And how about explicit CDC criteria for reversing gear and and reintroducing masking, distancing, and other limitations if a new surge arrives? They may exist, but I haven’t been able to find them.
States are free to impose their own indoor mask mandates, and Hawaii, Illinois, Oregon and Washington are keeping theirs. Several blue states have instituted an honor system, saying you can only stop wearing masks indoors if you’re vaccinated. Dream on! In January 37% of unvaccinated Americans, versus 75% of the vaccinated, said they “frequently” wore masks. Connecticut and California also still require masks in schools, health care facilities, nursing homes, jails and prisons, homeless and emergency shelters, and on public transit.
The CDC’s switcheroo may seem sensible to experts including Leana Wen and Ashish Jha – and to the American public. In a Yahoo poll as far back as January only 33% of Trump voters were at all worried about COVID-19, 89% of currently unvaccinated elderly people intended to stay that way, and 46% of all adults thought we needed to “get back to normal.”
In my opinion, though, the redefinition boils down to saying infections don’t matter, only severe disease. This amounts to flirting with the notorious herd immunity concept that Dr. Walensky herself vigorously opposed in late 2020. Some American experts have publically dissented from the new guidelines, notably top doc Eric Topol, whose latest article is titled “Once again, America is in denial about signs of a fresh Covid wave.” Dr. Eric Feigl-Ding tweeted: “MAGIC— we go from left map to right map in just 1 day!!! Hallelujah? ‘One day COVID will just disappear’ — never thought @CDCgov will gaslight us light this. @CDCDirector — what the heck are you doing?”
Concentrating on hospital capacity also means ignoring two crucial words: long COVID. We still don’t know how many Omicron patients will have prolonged symptoms, but I worry, along with some prominent scientists and clinicians. Especially having seen young patients of my own who are still tired and short of breath months after presumed Omicron.
In other CDC news, it was startling to learn that the CDC has been deliberately withholding vital pandemic information from the public. It’s been tracking the age, vaccination status, and race of COVID-19 patients and fatalities for more than a year, but keeping the data to itself, and also preferred not to reveal some key booster data. One expert commented, “The CDC is a political organization as much as it is a public health organization.”
No wonder the proportion of Americans who trust the CDC has fallen from 69% at the start of the pandemic to 44% now.
The word “endemic” gets tossed around a lot nowadays, with 55% of US voters thinking COVID-19 should be “treated as an endemic disease that will never fully go away,” like influenza. I agree that the flu is a good measure: the time to consider COVID-19 an endemic disease like any other, when we can let down our guard, will be when it’s killing more or less as many people as influenza, which in the US means 28,000 deaths per year, about 2000 a month. But even with the Omicron surge supposedly over, that many are still dying every couple of days. Until the endemic phase arrives we need to keep protecting people by encouraging vaccination, mandating masks in public indoor settings, and isolating infectious individuals. As I mentioned above, I lean negative on the hot button issue of masking children in schools, since classrooms are not where kids mostly get infected. If Paxlovid or other highly effective antivirals and medical consultants were easily, quickly, and universally available at your corner drug store, my mind could change.
COVID-19 cases, hospitalizations, and deaths have all been falling precipitously in the US, but Anthony Fauci predicts cases will soon rise again, though severe disease may remain low. An uptick makes sense, with the simultaneous arrival of BA.2, scrapping of mitigation measures, waning vaccine immunity, and low booster rates. But note: case numbers have always been unreliable in the US, and are increasingly useless as more and more patients get diagnosed only with unreported home tests. Instead, follow hospitalizations and deaths.
Post-pandemic antics abroadreaffirmed a vaccine mandate for everybody over 50, though letting them off with a silly €100 fine. In late March, though, Italy surrendered to the “endemic” temptation. As of April 1st regions will no longer be classified weekly by risk, Green Pass requirements will loosen, and face masks will only be required inside stores, theaters, transport, and sport venues. One month later the whole structure dissolves: no more Green Passes, face masks, or physical distancing. The sole vestiges: until June 15th older workers who want to work in person must be vaccinated or recovered, and until the end of the year workers in health settings and nursing homes must be vaccinated (as of early February 29,972 physicians were known to be unvaccinated, but only 2,254 had been suspended without pay as the law demands – many, though, were exonerated for having recently had COVID-19).
Some Italian experts approve of the plan, but I’m predictably with the many, from the country’s infectious disease guru to the Health Minister’s scientific advisor for the coronavirus, who think it’s a mistake. Retiring the Green Pass is fairly reasonable – it’s already been so successful at its task of incentivizing vaccination that only 8.7% of people over 12 haven’t had a shot. But scrapping face masks??? Cases of COVID-19 in Italy have doubled during March, and more Italians are dying per capita than Germans, French, or Brits. This is not the moment to stop masking. The president of Italy’s evidence-based medicine foundation, Gimbe, calls the idea “madness.” The government does say it will re-introduce the indoor requirement if a real surge threatens. I’d bet that moment will come before the de-masking decree goes into effect. And don’t expect to see my own bare face inside any stores or theaters for good while to come.
England: When Boris Johnson trashed COVID restrictions in late February, including self-isolation for infectious patients, a political motivation was clear – he’s hanging on to power with his fingernails amid myriad scandals and gaffes, including an idiotic comparison of Ukrainians to Brexiteers. Since then the number of UK cases has more than tripled, though hospitalizations and deaths (always lagging indicators) hold pretty steady.
China: Their famed zero-COVID policy fell apart a few weeks ago when surges occurred in multiple cities, most notably Hong Kong which since February 19th has seen more than a million cases and nearly 4000 deaths, out of only 7.5 million people. The underlying reason is that China pushed its workforce to the front of the vaccination queue, rather than giving precedence to older people. And though it’s vaccinated as many people per capita as Italy, it’s given 40% fewer boosters.
Israel: All those vaccine doses haven’t kept the BA.2 subvariant from spreading and now dominating in Israel, and haven’t kept cases from increasing since Green Passes have been largely abandoned. But the country has sensibly decided to nip a possible new surge in the bud by keeping an indoor mask mandate in place longer than planned.
My favorite new conspiracy theory
Meet Hydra vulgaris, a parasitic organism rumored to be found, live and wriggling, in COVID-19 vaccines. Read here about the osteopathic physician peddling this crap.