Pills, Profiteers, and the COVAX Blues

Capsules of molnupiravir

 Molnupiravir bursts onto the scene, boosters and mandates plod along, profiteers profit, Idaho screws up, pandemic benefits run out, and COVAX fizzles.

 

Treatment updates

Molnupiravir: There can’t be a human on the planet who hasn’t heard of the first oral antiviral for COVID-19. Merck’s molnupiravir, which we know about so far only from a press release, is being widely hyped as a game-changer or even as the final solution to the COVID-19 problem. Yes, OK, it’s nice that a simple pill can help COVID-19. But molnupiravir is no miracle drug, and it’s less effective than the monoclonal antibody products that are similarly aimed at high-risk patients with early COVID-19. The pill reduces hospitalizations by only 50%, the monoclonals 70-80%. And so far we have no idea whether molnupiravir shortens illness, relieves symptoms, or reduces long covid. What we crave is a pill that you take the day you test positive and it makes COVID-19 go away, like popping Bactrim for cystitis or penicillin for a strep throat. One day maybe, but I doubt this is the one. (Incidentally, the US government will be paying $700 for a 5-day course that probably costs less than $18 to produce.)

Within a week of Merck’s press release, American nutcases had decided that molnupiravir and ivermectin were the same thing! If you follow that link, check out the replies as well, they’re priceless.

RegenCov: One of molnupiravir’s biggest selling points is not having to go to a hospital-like setting for an intravenous infusion. But… since July you can get Regeneron’s antibody cocktail, in the United States at least, as 4 simple subcutaneous injections administered at one sitting in your doctor’s office. I was delighted to see this little-cited advance plugged in a recent Washington Post article. A trial directly comparing the intravenous and subcutaneous routes was completed in September, but its results haven’t yet come out. Even if the Merck pill is as good as the company claims, and gets approved and marketed instantly, I think many people, if properly informed, would prefer to get the shots. Of course a pill is easier to take, and could be prescribed during a remote rather than in-person visit. We’ll see how it goes.

A propos of RegenCov: the government of Tennessee has decreed that henceforth all monoclonal antibody treatments will be reserved for the unvaccinated. If you’re high-risk, vaccinated, and have a breakthrough infection, you’re on your own.

Ivermectin: OK, I know I said basta. But then The Guardian published a great article that I just have to pass on to you.

AZD7442: AstraZeneca has concocted its own monoclonal antibody combo, which according to a press releasereduced the need of hospitalization by 50% in high-risk outpatients. That’s less effective than the 70-80% reported for other monoclonals, making this drug’s only advantage that it can be given by intramuscular injection instead of IV infusion. But now that RegenCov can be given subcutaneously that’s less powerful a draw.

Remdesivir: Finally a study in outpatients. Not surprisingly – the earlier the better is the rule for antivirals – it seemed more effective than in inpatients, reducing the risk of hospitalization or death by 87%. That’s even better than monoclonal antibodies. But having to come in 3 days in a row for intravenous infusions is such a downer that I doubt remdesivir will get much traction among outpatients in the real world. Unless, that is, the oral and inhaled versionscurrently under development turn out to do just as well, which doesn’t seem the case so far.

 

Vaccine updates

The 3 COVID-19 vaccines used in the USA

SCB-2019: There’s a new kid on the block. The other day, out of nowhere, I caught a press release announcing a vaccine that’s entirely new to me. It’s an adjuvanted protein-based vaccine, like Novavax, and comes from a mysterious company called Clover Biopharmaceuticals. From what I see on Clover’s Leadership page, I’d guess it’s Chinese. The vaccine supposedly has 79% efficacy against symptomatic COVID-19 caused by the Delta variant, the only strain that counts, but no further data are available.

Novavax (NVX-CoV2373): The US Phase 3 trial is now available in preprint manuscript form. As with other Novavax trials, the topline efficacy is around 90% and the data are pre-Delta. But results like that have been coming through multiple times since early February. Why is this vaccine being slow-walked? 

One size fits all: A first timid step toward a universal COVID-19 vaccine has been taken with the launching of a Phase 1 trial of a multivariant mRNA product in the UK.

AstraZeneca: The United States/South American Phase 3 trial has now been properly published. The topline result was 74.0% efficacy overall 2 weeks after the second dose against any COVID-19, a surprising 83.5% in people over 65 (contradicting the relatively low effectiveness among the elderly in UK studies), and 100% in preventing severe disease. Remember, in this study the two doses were given 4 weeks apart, instead of the 12 weeks used in Europe and the UK. No clotting complications were observed, though with only 21,635 subjects none would have been expected.

Soberana: Cuba’s second home-grown vaccine is now claimed, like its first one, Abdala,  to have a topline efficacy of over 90%. Looking forward to seeing more details.

Pfizer boosters: As though we hadn’t already seen enough confusion, the CDC is now saying that adults ages 18-64 with occupational risk exposure, thus eligible for boosters, are defined as those who work in “close proximity to other people” and and have “unavoidable, frequent interactions with unvaccinated people.” How many jobs don’t involve close proximity to other people? The CDC is basically approving the booster free-for-all that already, given the lack of central vaccine registries in the US, was the reality on the ground. 

The crucial Israeli booster study has now been published, with no surprises: people over 60 who got a third shot of Pfizer were 20 times less likely to get COVID-19 during the Delta surge than people over 60 who got no booster, bringing their level of protection back to the 95% found in Phase 3 studies against the less troublesome wild strain.

Moderna boosters: The FDA is set to approve a half-dose booster six months after the second dose. As with Pfizer, it’s supposed to be restricted to the elderly and the vulnerable, but as with Pfizer in practice it will be the more the merrier. In Italy (and I assume the rest of the EU) a booster is authorized for everybody over 60, 6 months after dose 2, but at the moment it’s mix-n-match, with Modernas first doses and Pfizer booster. If the FDA approves the homologous Moderna booster as is expected, hopefully the EMA will follow. Worth mentioning that the EU is currently awash in Moderna – in Italy, at least, more than a quarter of the doses that have arrived are still sitting on shelves.

Johnson & Johnson boosters: People who had J&J, the least effective of the vaccines available in the United States, definitely deserve a booster (as do those who had the very similar AstraZeneca). I’ve long advocated Pfizer or Moderna second shots for both, and we now have excellent evidence that mRNA boosters stimulate far higher anti-SARS-CoV-2 antibody levels than a J&J repeat dose. But despite some previous hints from the FDA that it would recommend mixing and matching, an advisory panel instead went along with J&J’s predictable preference for a second dose of the original. It seems, though, that the FDA now plans to allow the option of a mix-n-match Pfizer or Moderna second dose – likely to be the preference of informed consumers. 

Similar data convinced the UK, AstraZeneca’s home country, to use only mRNA vaccines for boosters, and persuaded Germany to offer Pfizer or Moderna boosters to everyone who received the AstraZeneca vaccine, whatever their age or the date of their original vaccination.

Mandates for grownups: Obligatory vaccination is more motivating than anyone had hoped. On September 20^th, about 83% of New York State’s hospital and nursing home workers had had a dose of vaccine. A week later, when the state’s mandate went into effect, 92% had. And in New York City unvaccinated school employees flocked to drug stores and doctors’ offices after a mandate was announced, raising the number who’d had at least one shot from 68% to 95%; in the end only 8000 out of the system’s 150,000 employees had to be placed on unpaid leave. For once Trump’s Supreme Court is being a force for good, batting away legal challenges to vaccine mandates, based largely on a 1905 ruling upholding obligatory smallpox vaccination…

Myocarditis after mRNA vaccines: Yet another study, at Kaiser Permanente in Southern California, confirms low risk overall, only 5.8 cases per million after the second dose of Pfizer or Moderna. But we already knew that. The problem is the much higher rate in young men and, especially, adolescent boys. I remain very concerned by studies in theUnited States and Israel suggesting that teenage males were probably hospitalized more frequently due to the vaccine than they would have been from COVID-19. We’re talking one case per 6600-7000 after a second Pfizer dose, and even more with Moderna. I think male individuals 12-30 should get only a single dose of mRNA vaccines, since the vast majority of cases occur after dose 2. The UK and Scandinavian countries are doing just that, with a few going even further and suspending Moderna altogether in males under 30.

Mandates for children: The state of California is planning on mandating vaccines for all schoolchildren as soon as Pfizer gets full FDA approval for kids 5-11. I have to admit that the myocarditis story makes me a bit queasy, though it’s reassuring to know that younger kids will get only 1/3 of the adult dose. Remember, the vaccine will be approved for younger children based not on full Phase 3 trials but on laboratory tests showing it stimulates antibody production. 

Transmission from breakthrough cases: Since people with post-vaccine breakthrough COVID-19 are believed to have have lower viral loads and stay swab-positive for fewer days, they should rarely transmit the disease to others. A new study from the UK suggests this is somewhat less true in the Delta era. Contacts of vaccinated cases were 82% less likely to become swab-positive themselves when Alpha dominated, but they’re only 65% less likely nowadays. This is presumably because fully vaccinated Delta patients, unlike patients infected with earlier strains, turn out to carry as much virus in their noses at the moment they get sick as if they had never been vaccinated.

Waning vaccine protection, 6 new studies for those who are obsessed with the issue: 

-       In one mostly American study, Pfizer’s overall efficacy dropped over 4 months from 96% to 84%

-       In another, from Kaiser Permanente, overall effectiveness of mRNA vaccines against all infections, symptomatic or asymptomatic, fell over 5 months from around 90% to around 50%, though protection against hospitalization remained near-total. 

-       In Qatar, Pfizer’s protection from all SARS-CoV-2 infection, and from symptomatic COVID-19, fell to a dismal 12-28% after 5-7 months – but, again, protection against hospitalization and death stayed around 90%. 

-       A CDC study of hospitalizations was unique in finding that Pfizer’s protection against severe illness waned substantially after just 4 months, from 91% to 77% (Moderna’s stayed high, 93% and 92%). 

-       A large Israeli study of vaccinated healthcare workers has identified risk factors: neutralizing antibodies dropped more quickly in men than in women, in people over 65 than in younger people, and in the chronically ill than in the healthy.

-       In a study of anti-SARS-CoV-2 antibodies in a handful of individuals who were vaccinated early, the J&J vaccine lost much less effectiveness over time than Moderna or Pfizer products, and by 8 months had practically caught up with them.

-       That same study hints that a disconnect between antibody levels (which fall off sharply) and T-cell or cellular immunity responses (which remain nearly stable) may account for the prolonged protection against severeCOVID-19.

 

Singing the COVAX blues

COVAX, the World Health Organization’s attempt to get COVID-19 vaccines cheap or gratis to the global South, was a great idea, but the reality is falling far short, confirming the fears of skeptics. Not only are wealthy countries and vaccine manufacturers falling short on their donations, with only 15% of promised doses arriving at destination, but COVAX’s inability to support distribution infrastructure has led to hundreds of thousands of doses – even of AstraZeneca, which presents no particular logistical problems – being left on the shelf until they expired. COVAX banked heavily on Indian-made vaccines, so it was badly hit when India blocked vaccine exports last April. Only 330,000 doses have been distributed so far, but more than a billion more are expected to flood into poor countries by the end of the year – likely overwhelming local healthcare systems and risking massive wastage.

How about the AstraZeneca doses produced in the United States and unlikely to ever be approved? The original plan was to give away 60 million, until the contamination scandal broke in Emergent’s vaccine plant. The 75 million ruined doses of Johnson & Johnson got most of the publicity, but masses of AstraZeneca went bad as well – possibly, it seems, the entire supply. The US cherry-picks its recipients: thumbs down to Venezuela, 3 million Pfizer doses each to Pakistan and the Philippines, 1.5 million Johnson & Johnson to Africa with promises of another 17 million, 2.5 million Moderna to Taiwan. The US has given away at least 120 million doses so far, and should soon ship half a billion more to COVAX for distribution. Unfortunately those doses are all Pfizer, which requires a cold chain and precision organization beyond the capacities of many low-income countries. 

Further complicating the work of COVAX, Africa lacks not only doses and infrastructure but popular trust in vaccines. Hopefully that hesitancy will shrink when doses arrive and vaccination campaigns start in earnest. 

North Korea is a special case. It hasn’t started a vaccination campaign at all, and turned down the 3 million doses it was offered by COVAX at the end of August. Its border closings have been so effective, it claims, that the country hasn’t seen a single case of COVID-19.

 

Shkreli Awards

Martin Shkreli, complete with smirk

The Lown Institute picked out 10 of the most egregious pandemic profiteers for their 2020 “Shkreli Awards,” named after the guy who raised the price of an antiparasitic drug costing pennies to make from $13.50 a pill to $750 (you read right).

Rather than taking the trouble to paraphrase them, I’ll just cite the Lown people verbatim:

1. Federal personal protective equipment task force gives lifesaving supplies to private companies to distribute, causing bidding wars and delays. 

2. Drug company takes nearly a billion dollars in taxpayer funding to develop its COVID-19 vaccine, then sets highest price of any vaccinemaker.

3. Hospitals with extra beds refuse to take uninsured patients from neighboring hospitals that are overrun.

4. Nursing homes fail to protect vulnerable Americans from COVID-19.

5. Pharma firms compete for profit instead of cooperating on COVID-19. 

6. Hospital CEO pens op-ed justifying high vaccine prices; neglects to disclose $487,500 received in stock options and other compensation as a Moderna board member.

7. Hospitals punish clinicians for wearing masks and speaking out on COVID-19 safety issues.

8. Connecticut doctor uses town’s COVID-19 testing sites to bilk residents. 

9. Pandemic profiteers peddle fake and potentially harmful COVID-19 “cures.”

10. Private equity–backed companies spend millions to protect surprise billing while cutting physician pay and pocketing relief dollars. 

 

Stable geniuses of a feather flock together

Former FDA director Scott Gottlieb

From the fellow who headed up the US Food and Drug Administration for 2 years under Donald Trump comes some of the stupidest advice I’ve seen coming from a high health official:

"If you are vaccinated in a high prevalence area, in contact with virus, you think you might have the virus because you have mild symptoms--be prudent, get tested, maybe wear a mask especially if you are around a vulnerable person," says @ScottGottliebMD. pic.twitter.com/LFlMffkfe9

MAYBE wear a mask? A person with known SARS-CoV-2 exposure plus symptoms should not just be wearing a mask but be in strict self-isolation – regardless of whether they’re vaccinated.

 

Running out

Sleeping arrangements in a homeless shelter

Three crucial elements that have helped Americans make it through the pandemic are now gone. 

First – happy Labor Day! – federal supplemental unemployment benefits evaporated on the holiday that supposedly celebrates workers. At least 7.5 million people lost their benefits entirely, and several million more saw them drop. The unemployment rate has fallen from its dreadful pandemic peak of 14.8% in April 2020 to 4.8% this September, but that’s still more than a third higher than what it was just before COVID-19 hit, adding up to about 2 million more people unemployed.

Second, insurance companies have largely stopped waiving co-pays and deductibles for medical care related to COVID-19, with 82% of insurers making patients now chip in toward their own hospital bills. One of the excuses they offer is that vaccines are effective and widely available – but they undermine that reasoning by making everybody pay, even fully vaccinated people hospitalized for breakthrough cases and kids not eligible for vaccines. Bills of over $15,000 are anticipated. Even in 2020, when the waivers were in place, many patients had to pay thousands of dollarsfor a hospital stay. The absurdities of the American health care coming home to roost… (Some insurers are also starting to raise premiums for people who refuse vaccines. I approve.)

Then there’s rent relief and eviction moratoriums, which have similarly largely dried up. That will swell the ranks of the homeless, and homeless shelters are crawling with COVID-19.

 

The Idaho paradox

The Delta wave was so awful in mid-September that all the state’s hospitals instituted formal rationing of care, turning desperately ill patients away from the ICU if they seem unlikely to survive, and giving them “comfort care” instead, i.e. letting them die. Desperate times call for desperate measures, right?

In fact, Idaho officials have been working overtime. Here’s how:

In the largest health district in the state, which includes the capital and its surrounding counties, they fired a 15-year veteran of the Health Board because he supported mask mandates, and replaced him with a pathologist who has called COVID-19 vaccines “fake vaccines” and “needle rape.”

The state’s House of representatives considered coming back into session solely in order to pass a bill banning mask mandates for hospital workers. In the end it didn’t happen, but still…

Governor Brad Little issued an executive order forbidding state universities and colleges to require vaccines. He also considered suing President Biden over OSHA’s vaccinate-or-test requirements, but seems to have given up on that one.

Patients are doing their part too, according to a Facebook friend who tells of an Idaho physician who has “severely ill patients who refuse to be tested (or treated) for covid, because they don't want to contribute to the statistics of covid cases or deaths because that would ‘help’ Biden.” Throwing themselves on a sword for Trump!

 

Variant watch

Delta: We already had hints from Scotland that the Delta variant might be more aggressive as well as more contagious, and now English data agree: as compared with the Alpha variant, people infected with Delta were twice as likely to wind up in the hospital. 

Lambda (C.37): Spreading some around South America. It may be more contagious than the wild strain, but doesn’t hold a candle to Delta.

Mu (B.1.621): Still merely a Variant Of Interest, not a Variant Of Concern, first spied in Colombia back in January. It is somewhat resistant to vaccines, but doesn’t seem to be more contagious or more virulent, and can’t compete well enough with Delta to cause surges either in the United States or elsewhere.

C.1.2: This one popped up recently in South Africa and has been seen sporadically around the world, but hasn’t yet been given a Greek letter or a WHO classification. I wouldn’t waste mental energy on it.

 

A sad tale told by an idiot