Vaccines new and old, bicontinental journalistic flops, this “post-pandemic?” world, long COVID, vaccine profits, Presidential COVID-19, and a touch of madness.
N-acetylcysteine: The armamentarium of medications to treat severe COVID-19 continues to expand. After sabizabulin, mentioned in my last post, now we have a high-tech version of acetylcysteine, a decades-old expectorant that in the US is mostly squirted down the tubes of patients on respirators but elsewhere is commonly ingested in liquid form – in Italy one brand name is Fluimucil – for cough. Acetylcysteine can also be lifesaving for paracetamol (acetaminophen) overdose. People have been proposing it as a possible COVID-19 treatment since early in the pandemic, and now there is some concrete support from a tiny but placebo-controlled and randomized study in severely ill hospitalized patients, accepted for publication in a high-level journal. Patients were given a single intravenous infusion of either placebo or an acetylcysteine/dendrimer compound specially designed to bind to activated macrophages (inflammatory white blood cells). Inflammatory markers in the blood of drug-treated patients began to fall within days, and 2 months later 3 out of 17 of them were dead, compared with 4 out of 7 placebo patients. This was only a Phase 2 pilot study; hopefully the results will hold up in a larger Phase 3 trial.
Natural immunity: According to a prepublished study from Qatar, having been infected with Delta or earlier variants gives virtually no protection (we’re talking 15%) from symptomatic infection with the Omicron BA.4 and BA.5 subvariants. Having had earlier versions of Omicron did provide some immunity against 4 and 5, but only 76%, meaning that plenty of people infected during the giant winter surge are susceptible to reinfection. Too few cases were involved to analyze how long natural immunity lasted or how effective it was against severe disease or death.
Post-Paxlovid rebound: I recommend an excellent article by Jeremy Faust, where he guesstimates from personal observation that it’s occurring in not 1-2%, not even 5-6%, but 15-35% of people who take Paxlovid. In his opinion the main reason is that the drug may function differently in people who have been vaccinated (the original trials were done in unvaccinated patients), while also suggesting the recent variants may have better comeback abilities and we may be treating people too early. He emphasizes the risk of spreading contagion, and the need to extend the patient’s isolation period. He says young healthy patients have been taking Paxlovid in the US. I didn’t know this, and it’s a bad thing – we have evidence that the drug gives people under 60 virtually no benefit.
|Patricia Neves and Ana Paula Ano|
Girl stuff: A pair of 40-something female Brazilian scientists who happen to be best friends are working on a new kind of mRNA vaccine that will be self-amplifying, thus requiring only a minuscule amount of raw material and making the vaccine cheap and convenient for the developing world. Even cheaper because the team plans to provide the recipe to the world free of charge – something the big players, Moderna and Pfizer, have steadfastly refused to do. Human trials won’t even reach Phase 1 for months, though, and this vaccine will likely face the same storage and distribution barriers as its competitors.
Novavax: After what seemed like an endless gestation, Novavax is born, achieving FDA authorization for emergency use in the USA as a two-dose primary series based on 90% efficacy against the wild strain of SARS-CoV-2. Some fantasize that its conventional technology will win over many of that 10% of American adults who are hard-core antivaxxers. As I’ve said before, I doubt it – with others – and suspect its chief value may be as a booster to mRNA vaccines. The good news is that a third dose of Novavax given to some trial participants 8 months after the second one seems to have induced neutralizing antibodies against Omicron BA.5. The bad news is that, like the mRNA vaccines, Novavax can probably cause both myocarditis and pericarditis, though the company plays down the risk. According to the FDA’s briefing document, 4 of the 5 cases within 10 days of a dose were in male volunteers younger than 30, though no denominator is provided.
A double bill from Moderna: I said last time that Pfizer has a fall 2022 booster in either hand. Now Moderna does too. Both are bivalent and are composed of spike protein mRNA half from the wild strain and half from Omicron. The first is their original candidate, now called mRNA-1273.214, which is made with with Omicron BA.1 but also spurs neutralizing antibodies against BA.4 and BA.5. The other, mRNA 1273.222, uses BA.4-5-strain mRNA instead and hasn’t yet been fully tested.
Pfizer dose 4: In 48 healthy older Israelis, anti-spike IgG antibody levels soared after a second booster, going from 3775 to 28,708, about the same peak level as after the first booster 5 months earlier. The researchers didn’t measure neutralizing antibodies. We don’t know how quickly those levels fall, though we do know that protection against infection only lasts 4-6 weeks.
Schoolkids: A study from Singapore confirms good protection from vaccination with Pfizer in 5-11-year-olds. But, as in Israel, it waned fast. The vaccine was 70% effective against PCR-confirmed infection 7-14 days after the second dose, but by 30-59 days its effect had already fallen to 60%, and 60+ days after dose two it was just 43%. Protection against hospitalization was over 80% for 2 months, with no longer-term data. About 40% of American children in this age group have been vaccinated – for once similar to Italy.
Little kids: The vaccination campaign for children under 5 continues to lag far behind expectations in the US, with only 17% of parents of children under 5 saying they’ve either vaccinated their kid already or intend to soon – down from 31% in January. And 43% say they definitely never will. No vaccines have been approved for this age group in Italy.
Boost now or wait?: Everybody’s asking me whether to get a second booster now or wait until the fall when Omicron-specific ones will come out. Neither I nor anyone else has had definitive answers, but since by now we’re only two months away from the arrival of the anti-Omicron boosters in Europe, including Italy, even less in the US, I’ve changed my mind and just say no… What is clear is that the two-thirds of Americans 18-64, the third of Americans over 65, and the third of Italians 20-50 who haven’t gotten any booster should go grab one now, since without it even the “fully vaccinated” are unprotected against Omicron of whatever flavor.
Worst headline of the month, as tweeted by Eric Feigl-Ding
What was the LA Times thinking when they plastered this headline on Mary McNamara’s piece? Fortunately they changed it within days to “Covid was my vacation souvenir. The brain fog is all too real.”
While much of the Western world is making like it’s 2019, the coronavirus has other ideas. To the point that WHO chief Tedros Adhanom Ghebreyesus has felt it necessary to scream danger from the rooftops, warning people that “The virus is running freely,” “covid-19 is nowhere near over,” and urging expansion of testing, vaccination (especially boosters), and treatment.
Expansion ain’t happening, though, on the contrary. Dedicated COVID-19 funding is in the process of running out in the US, Italian emergency services are long past the crisis point, one out of 17 people in the UK had COVID-19 during the week ending July 7th, and hospitalizations are soaring in virtually all countries that provide data. In Italy, a leader in vaccinations, the booster campaign has slowed down dramatically in the last 4 months even though more than a third of adults still haven’t had one. The message doesn’t seem to have sunk in that Omicron brushes off two doses like flies.
In the US, I consider Rochelle Walensky’s CDC missing in action in the face of surging COVID-19 cases, hospital admissions, ICU occupancy, and now deaths. Somebody in the Biden administration must agree, if they’re reorganizing the Department of Health and Human Services to elevate the Administration of Strategic Preparedness and Response to an independent agency at the level of the CDC and the FDA and having it lead America’s battle against the pandemic.
I must say that Italy isn’t doing any better, with just as many deaths per capita as the US even though nearly twice as many people have had vaccine boosters; wider use of antivirals in the US may be what’s saving those lives. And the situation in Italy’s hospitals is dire. I’m damned if I can understand how official figures can claim that on July 19thonly 16.7% of available COVID-19 beds and 7.5% of available COVID-19 ICU beds in the Lazio region were occupied, when on the very same day La Repubblica reported (Cronaca di Roma, p. 4) that more than 70 patients were parked in the Emergency Room of each of Rome’s largest hospitals waiting for a bed, and that all 850 of the COVID-19 beds that have been opened up in the last 2 weeks were occupied. A week earlier, according to the same newspaper, 55 ambulances were sitting outside ER doors and more than 100 emergency calls for ambulances were being totally ignored every day.
Long COVID updates
Prevalence: An American study following 173 patients after COVID-19 they contracted during the first wave found that half of them still had at least one symptom a year later, most commonly fatigue and/or shortness of breath, and one in 4 still had symptoms 2 years later. Patients who had been hospitalized were only slightly more likely to have persistent symptoms at 12 months (53% vs. 48%). These figures seem dire, but there’s a catch: 500 patients were invited to participate, but two-thirds declined. The researchers don’t specify exactly what they told the patients, or how the participant and non-participant groups compared, but it seems to me likely that people would be more likely to agree to be interviewed if they had long COVID. It is also unclear how relevant a study of patients from the pre-vaccine, pre-variant era is to the current phase of the pandemic.
UK researchers using in-depth cardiac evaluations found that more than half of patients hospitalized for COVID-19 had evidence of myocarditis one-two months after discharge, one in 5 had scarring of the heart muscle, and many had persistent kidney malfunction and signs of inflammation. The brief follow-up in this study is a major limitation, as are two characteristics shared with the American one: difficulty recruiting participants and completion relatively early in the pandemic.
Origins: According to an interesting new preprint, intact spike protein could be detected in the blood of 60% of 37 COVID-19 patients who continued to have symptoms 3 to 12 months later, but in none of 26 patients whose acute disease resolved within weeks. A few patients were carrying other bits of virus in their blood as well. The researchers think their findings support the hypothesis that persistent live virus is at the root of at least some cases of long COVID. They also thought the spike protein itself might be directly causing symptoms, by overstimulating the immune system, but were unable to document this when they measured proinflammatory cytokines in the blood. The finding of immune complexes in the autopsied brains of 9 people who died in the first COVID-19 wave may support the immune overstimulation theory.
Treatment: Centers in Germany and elsewhere have been offering long COVID sufferers apheresis, a form of blood cleansing intended to filter out microclots from the circulation, under the theory that small vessels clogged with tiny clots are at the root of long COVID symptoms. The leading practitioner, Dr. Beate Jaeger, promises that “The good therapy results so far will soon be available as a study.” I find the microclot hypothesis convincing, and don’t rule out that her treatment may work, though certainly not on everyone. But I am concerned that Dr. Jaeger apparently told the BMJ she had treated “thousands of patients,” while her website says “more than 100.” And even more concerned that she isn’t testing her treatment in a controlled trial, claiming variously that it’s too expensive and that “Trials take too long when the pandemic has left patients desperately ill.” But if it is true that, as she claims, her patients can go “From wheelchair to walking in just a few weeks” then a proper trial would only take a few months to complete. And I don’t honestly see why randomizing half her patients to a sham procedure would be so expensive. Some other apheresis centers are ethically questionable – scientifically, too, since they still prescribe hydroxychloroquine for COVID-19!
Vaccine effects: Veterans Administration researchers have published the latest study finding that “breakthrough infections” in fully vaccinated people are only a bit likely to cause long COVID than infections in the unvaccinated. Six months after their infection, vaccinated patients were 25% less likely to have fatigue, 15% less likely to have cardiovascular problems, and 15% less likely to have any long COVID symptom. The only complications at substantially lower risk were pulmonary problems and clotting disorders. This study was done in January-October 2021, before Omicron, booster doses, or outpatient antiviral therapy, so it has limited relevance to the present phase of the pandemic. I was puzzled to see the first author of the study featuring in a misleading Twitter thread not the comparisons with unvaccinated COVID-19 patients but comparisons with a healthy uninfected population.
The vaccines that laid the golden eggs
Curious how much the vaccine-sellers have made off the pandemic? This will give you an idea: Pfizer, the company that gave us not only the first effective vaccine but also the first effective treatment, doubled their income in 2021 over 2020: $81 vs. $41 billion gross, $22 vs. $9 billion net. And that’s before Paxlovid came out – just imagine the prospects for 2022. Moderna closed 2021 with similar profits despite selling only 673 million doses to Pfizer’s 2.4 billion, by charging higher prices and taking a 70% profit margin.
Science journalism Italian style
I was delighted the other day to see a headline in Il Messaggero about oral antivirals: “COVID, the antiviral weapon against the summer boom, ‘But they don’t prescribe it.’” The failure public system GPs to prescribe Paxlovid happens to be my current pet peeve. But reading further down I got even more peeved, at the journalist.
She correctly points out that only 21,000 of the 600,000 available courses of Paxlovid have gone into patients. And she correctly blames the government for not telling GPs last April they could now prescribe the drug themselves instead of sending patients to the hospital.
But she herself seems to be unaware of a vitally important later change in antiviral use: a vast expansion of eligibility. From February to May, only people who were immunosuppressed or otherwise gravely ill could get antiviral treatment. As of June 1st, though, everybody who is at increased risk because of asthma, obesity (not “morbid obesity” as she writes), or other chronic illnesses, has a right to Paxlovid. Most crucially, the increased risk category now includes everybody 65 years and up!!! The government’s failure to inform GPs of this change is even deadlier than their omission back in April. The journalist had the opportunity to let older COVID-19 patients know they now have a right to effective treatment, and I consider her failure to do so criminal.
I have always said that science journalism is an unknown concept in Italy – with one knowledgeable local even listing“Seven reasons why Italian science journalism is poor.” This is the umpteenth proof.
Still talking lab leaks?
A pair of papers in Science, one based on analysis of the SARS-CoV-2 genome and the other on analysis of cases and animals at and around the Huanan Seafood Wholesale Market in Hunan, claim to have proven that the market was the source of the pandemic. This should be the final nail in the coffin of the theory that the pandemic originated in a virus that leaked from a Chinese laboratory. But given the insane politicization that pollutes everything related to the pandemic, that theory is unlikely to go away.
A tale of two COVIDs
|Trump tearing off mask, Biden in April|
Both pandemic-era American Presidents have had COVID-19, and some of the contrasts in their cases are interesting. The most obvious is the difference in severity, with Trump barely avoiding the ventilator and Biden sailing through with mild symptoms, at least at first – as I write his post-Paxlovid “rebound” has just been announced. It supposedly consists in just a positive antigen test, without any symptoms, but there’s no guarantee that will hold. Anthony Fauci, for instance, was sicker with “rebound” than he had been when he first fell ill, though he did escape hospitalization. Assuming Biden won’t follow in Fauci’s footsteps, one can only say thank you vaccines, thank you boosters, and thank you antivirals. Trump’s life may have been saved by monoclonal antibodies, but he would likely never gotten anywhere near as sick if Paxlovid pills had been available at the time.
The emphasis on how mild Biden’s symptoms are, how he’s working long hours despite his illness, etc., is a political choice, and it doesn’t necessarily send the best message. People should know that COVID-19, even of the Omicron variety, can make people quite sick, can cause long COVID, and should be avoided if possible. Far from being “just a flu,” Omicron has killed about 200,000 Americans thus far.
The poor guidance being provided by the CDC is also rightly being highlighted by many experts. “For instance, the White House said Biden would remain in isolation until he tested negative for the virus, going beyond CDC guidance.” My own advice to patients goes even further: isolate for 10 days even if you’ve gone negative on an antigen swab. Antigen tests are notoriously poor at detecting Omicron, live virus has been detected in Omicron patients as long as 14 days after symptom onset, and rebound cases risk infecting others even if asymptomatic.
Much has also been made of the care Biden took to avoid infection, in contrast with the notoriously mask-adverse Donald – particularly that anybody coming in contact with him had to test negative (including Mohammed Bin Salman?). But those tests are notoriously lousy, asymptomatic infections can be highly transmissible, and Biden himself has gotten sloppy about masks these days, not just before his diagnosis but also when he was supposed to still be wearing one afterward.
Kosher vitamins can prevent and cure COVID-19, including “Delta, as well as Omicron strains.”
Drinking your own urine is just as effective.
One company that received a warning letter from the FDA still hasn’t taken down the claim that its iodine-based CofixRX nasal spray “reduces viral load of Sars-CoV-2, the virus that causes Covid-19, by 99.9% in under 45 seconds.”
And the outfit selling a nasal spray containing Iota-Carrageenan, derived from seaweed, still hasn’t quit claiming their product can prevent COVID-19.
But other FDA warning letters have worked:
- Multiple sites promoting CBD to prevent or treat COVID-19 have removed those claims.
- So have the manufacturers of a salt water mist product who had claimed that “A Harvard study demonstrates it may have a protective effect against airborne viruses like COVID-19.”
- And the makers of mullein leaf tea, who once advertised “everything you need for cold/flu or COVID management at home in one click,” adding “Don’t just wait until you’re bad enough to go to the ER!! Get better instead!”
- The FDA has even gotten some Indian websites to stop claiming, for instance, that “Ayurvedic medicines obstruct the replication process of the Coronavirus and mitigate its infection by increasing the body’s fighter immune cells.”
Coincidentally, two scientists have just reported that even products containing banned ingredients are often not removed from the market after warning letters from the FDA.
I’ll close with a zinger that drew a nice comment on Twitter: “This genius eugenicist thinks that diseases don’t actually exist. The only problem is weak people.”
Hi Susan, another great post covering just about everything. Thanks. Glad to see bivalent vaccines will be ready for the autumn, I wonder what the take up will be? The tale of two presidents is excellent!ReplyDelete
Thanks so much! Especially about the tale of two presidents, which I obviously had to toss together at the last minute. I have a feeling the bivalent vaccines may get more customers than the second boosters did. This based largely on what my friends and patients are saying, tho they're certainly no random sample of the population. I'll certainly leap at the chance myself. Unfortunately that will be a month or more after the US. And probably they'll go in age order so I'm unlikely to get one before November.Delete