Sporting Chances, Floating Clouds

 

A rare street demonstration in Japan

Vaccines and aerosols, leaky labs and rebaptised variants, athletics from New York to Tokyo, with a sprinkling of nuttiness and alternative facts.

 

Treatment updates

A gut organoid infected with SARS-CoV-2 (white spots)

Organoids to the rescue: Researchers have developed a fascinating model for testing potential COVID-19 therapies: clouds of microscopic artificial organ-like particles that can be soaked in virus, then slathered with vast varieties of chemical concoctions to see whether any enable the miniature lungs (lunglets?) or intestines (gutlets?) to survive. Alas, thy’ve come up with nothing actionable thus far…

Natural immunity: The latest article describing immunity to reinfection following COVID-19 concludes that there was “substantially reduced risk of reinfection” over 10 months in nursing home residents and staff, but its stated results don’t really support this conclusion. For the residents, yes – those with COVID-19 antibodies at baseline were 85% less likely to have a positive swab afterward. But the staff only had 61% protection, the lowest ever reported. Their calculations seem off, however – I recalculated protection at 87% for residents and 79% for staff, though with only 14 cases none of those percentages are really reliable. Notably, none of the 14 died or needed hospitalization.

Antibody nose candy: Six months ago I mentioned a monoclonal antibody nasal spray being developed by Philadelphia researchers. That project has never been heard of since, but a Texas group grabbed the baton, engineering an antibody able to counter the original virus plus Alpha, Beta, and Gamma variants, and showing that a single dosecan prevent and treat COVID-19 . . . in mice. There’s many a slip between the animal lab and your local drugstore.

Decoy nose candy: I’ve reported on at least 3 different tpes of wannabe anti-COVID nasal sprays, but I missed apreprint from April describing yet another one: “a soluble form of angiotensin-converting enzyme 2 (ACE2)—referred to as a decoy.” It neutralizes several strains of SARS-CoV-2 in testtubes, works against mouse COVID-19, and successfully infiltrates the airways of macaques. Again, many a slip.

 

Vaccine updates

Alternative facts: Ummm… As the Guardian article explains below this headline, 2 weeks after the second dose Pfizer was, yes, 88% effective. But AstraZeneca only 60%. Another weird bit of jingoistic spin originating in the UK, this time from an ordinarily impeccable source.

Human challenge trials: Two sets of Brits are quietly plunging ahead with studies purposely infecting volunteers with SARS-CoV-2. In Oxford at least they’re only giving the virus to people who already had COVID-19. But at Imperial College London they’re deliberately exposing virus-virgin subjects. I continue to consider it grossly unethical to give healthy people a potentially deadly virus for which we have no decent treatment and that can lead to long-term symptoms even in people with mild initial disease. 

Booster upon booster: Should we worry about all those Brits, Americans, and  health workers like myself who had COVID-19 vaccines in December-January? In my reading of ongoing research, our immunity is likely to last at least a year or two, making further boosters unnecessary for the time being. But the spread of variants resistant to AstraZeneca, especially Beta and Delta, leaves people who received that particular vaccine at high risk of infection – probably what’s fueling the current surge in the UK. A supplemental dose of Pfizer following AstraZeneca might be just what the doctor ordered.

AstraZeneca: Descriptions of severe clotting problems caused by the AstraZeneca vaccine worldwide are only now starting to be published, in the form of case series from February-March, reporting 11 patients in Germany and Austriaand 5 in Norway. Since there have been at least 700 such cases by now, these articles mainly demonstrate how slow medical journals are in getting out vital information. A Canadian reported treating 3 patients with “vaccine-induced immune thrombotic thrombocytopenia”: high-dose intravenous immune globulin plus non-heparin type anticoagulants, supplemented in one case by therapeutic plasma exchange. It was technically a success, but 2 of the 3 patients were left severely handicapped.

Johnson & Johnson: The newly published report of their Phase 3 trial mainly confirms what we already knew: efficacy against COVID-19 of 66%-67% by 2 weeks, efficacy against severe or critical COVID-19 reaching 85% after 4 weeks, relatively mild side effects. Against the vaccine-resistant Beta variant (B.1.351), the corresponding figures were a respectable 62% and 82%. J&J was also OK at preventing asymptomatic infection: 66%, much better than AstraZeneca, much worse than Pfizer or Moderna. 

…but this vaccine may be harder to get your hands on now that the FDA has had to order 60 million doses from that infamous Emergent factory to be tossed in the trash. They haven’t yet decided whether to let the factory reopen.

Sinovac: Details of the Brazilian Phase 3 trial for their CoronaVac brand vaccine, made public as a non-peer-reviewed preprint, have now revealed several of its limitations: fewer than 10,000 analyzeable volunteers (other trials had 30,000-40,000), almost all under 60. Overall efficacy was confirmed at 50.7%, and its much-touted “100% efficacy” in preventing severe disease turns out to be based on only 6 cases, one fatal. Real-world studies have reported strangely variable effectiveness against mortality: 98% in Indonesia, 80% in Chile. 

The Chinese are planning on giving CoronaVac to children as young as 3, based on Phase 2 studies showing kids develop antibodies. Apparently Moderna and Pfizer are planning to ask for FDA approval on the same basis. 

Pfizer: My college classmate Lee Anne Willson, a scientist in an entirely different field (astronomy), has done fascinating and important reanalyses of the following data from the giant Israeli effectiveness study:

 

Protection against	%effective	#per/day for 100,000 people, unvaccinated	#/day for 100,000 people, vaccinated
Infection	95.3	91.5	3.1
Asymptomatic	91.5	40.9	1.8
Symptomatic	97.0	32.5	0.8
Hospitalization	97.2	4.6	0.3
Severe	97.5	2.7	0.2
Death	96.7	0.6	0.11

 Her novel observation is that though vaccinated people have a much lower risk of catching SARS-CoV-2 or falling ill with COVID-19, breakthrough cases tend to be particularly severe.

Here are the numbers. If you are unvaccinated and are infected with SARS-CoV-2, your probability of hospitalization is 5% and your probability of dying is 0.7%. If you are unvaccinated and become ill with COVID-19, those probabilities are 14% and 1.8%. If you are vaccinated and have an breakthrough infection, your probability of hospitalization is 9.7% and of dying is 3.5%. If you develop symptomatic COVID-19 despite being vaccinated, the corresponding risks are very high indeed: 38% and 14%.

Prof. Willson has proposed a probable explanation: vaccinated people with breakthrough COVID19 are more likely to have an impaired immune system. The impairment is a double whammy – you are both less protected by the vaccine, and less able to fight off the virus if you catch it. 

Prof. Willson points out that these numbers show one reason why it is so important to get a large fraction of the community vaccinated and bring down the number of active cases: to lower the risk that immunocompromised people, a category that probably includes 4% of Americans, will encounter someone who is contagious.

(…note that the “rare” American cases of heart inflammation reported in young people following Pfizer or Moderna vaccines turn out to have reached 226, with only 81% fully recovered. Judging by the experience in Israel, where 2 out of 60 cases were fatal, one can guess that this complication will likely have caused a few deaths by now.)

News sources count: Someone on Facebook suggested I check out Robert F. Kennedy, Jr. for reliable vaccine information. On Twitter I quickly saw that a better word is disinformation. He features vaccine side effects – fair enough, so do I – but intersperses real news with nonsense. Take his claim that COVID-19 vaccines have caused 5,165 deaths in the USA – I’d estimate the correct figure at around 40: 3 related to clotting complications from J&J, 7 or 8 from myocarditis, and another couple of dozen from flu-like side effects in the frailest elderly. Then there’s the dubious claim in the above headline, that vaccines disseminate poisonous substances throughout the body. It is true that spike protein migrates from the vaccine site, and that spike protein contributes to organ damage in people with COVID-19, but the quantity produced by vaccines is infinitesimal – there’s 40,000 times more spike protein in COVID patients’ blood than in vaccinees’, and it is a more toxic form. This bit of pseudoscience from Canadian immunologist Byram Bridle has been exhaustively and variously debunked. Mr. Kennedy also has it in for Bill Gates, saying with a straight face that the founder of Microsoft is scheming to get rid of real food, replacing it with “GMOs, fake lab-made ‘meat’ + artificial cheese—all made with patented technologies from which he’ll make millions.”

Just desserts

Remember Steven Brandenburg, the Wisconsin pharmacist who back in January trashed 500 doses of the Moderna vaccine for the good of humanity? He’s been sentenced to 3 years in prison for “attempting to tamper with a consumer product.” Fortunately only 57 of the doses he’d left out of the fridge were ever injected into people’s arms, and even more fortunately the doses were probably still functional, though no one seems to have measured the antibody responses.

Mixing-‘n’-matching: Alert blog readers may recall that I’ve always been against what’s technically known as heterologous prime and boost, but I’ve been coming around. On the positive side, because of early reports that AstraZeneca vaccinees achieve particularly high antibody levels when they get Pfizer for their second dose. And, on the negative side, because the fairly high rate of clotting complications of AstraZeneca in the young makes it prudent to avoid putting them at risk twice. There really ought to be more real-world data out there, since Germany and France have been swapping out AstraZeneca boosters in favor of Pfizer for months, in people under 60, but I haven’t seen any. Italy is now about to follow in their footsteps, partly spurred by the tragic death of an 18-year-old girl following AstraZeneca. I really wish they’d go a step further, as does Canada, by offering Pfizer as dose 2 to everybody who started with AstraZeneca.

The Talladega Superspeedway in Alabama

Persuading the reluctant: It’s mostly carrots. In African-American neighborhoods, Shots at the Shop (black-owned barber shops, that is). In New Jersey, Shot and a Beer. In Washington State, Joints for the Jab. In Alabama, the chance to drive your own car around a Formula One racetrack. In New York City, walk-in sites in subway stations with MetroCard giveaways. All over the US: free Ubers and Lyfts to vaccine hubs. But the Houston Methodist hospital network is (rightly, in my opinion) turning to sticks: unpaid leave for heel-draggers, to be followed if necessary by termination – a judge has now thrown out a lawsuit against the hospital by anti-vax nurses. Washington D.C. and Maryland hospitals will likely follow suit. So will Rome’s Lazio Region where days from now, two months after the vaccine mandate for health workers, 300 unvaccinated holdouts among 28,000 doctors and nurses will be kicked off the wards and have their pay slashed if they still haven’t complied.  

 

Non-sequitur of the month

The California judge who notoriously compared assault weapons to Swiss Army Knives buried a gratuitous nugget of fake news in his opinion. He was writing a week after a shooter in San Jose killed 9 co-workers; the number of deaths due to vaccines in California can be guesstimated at 3 or 4.

 

 

A variant by any other name

The World Health Organization has decided to get rid of the confusing names of the variants in favor of Greek letters, assigned in order of discovery, both for the sake of simplicity and to not stigmatize Wuhan, South Africa, or anywhere else. The inscrutable numbers do remain for scientific purposes, but otherwise:

-       The UK variant (B.1.1.7) will henceforth be known as Alpha

-       The South African one (B.1.351) as Beta

-       The first Brazilian one (P.1, also detected early in Japan) as Gamma

-       The main Indian (B.1.617.2) as Delta

-       The Californian (B.1.427) as Epsilon

-       A second Brazilian one (P.2) as Zeta

-       The one that showed up in the UK and Nigeria (B.1.525) as Eta

-       The one first found in the Philippines (P2) as Theta

-       The New Yorker (B.1.526) as Iota.

-       A Indian one (B.1.617.1) as Kappa

Up next are lambda, mu, and nu. (Nu? From Israel maybe? Sorry, stupid joke…)

 

Airborne aerosol spread 

I’ve never been convinced that minute virus-bearing particles can waft across vast spaces and remain infectious at length – so-called airborne spread. But even so I was a little surprised when I read a brand-new, prestigiously published guideline proposal from two aerosol proponents and an New York Times Op-Ed from another, and saw that neither cited any new evidence at all, only the same 3 tales that people have been repeating for many months. The guideline authors call their work a “study,” but actually it’s just a theoretical model. I’m tired of big conclusions being drawn from theoretical models.

Of those 3 episodes, what seemed the most convincing evidence of long-distance aerosol spread wasn’t in a restaurant in China or in a choir rehearsal in Washington State (see an old Stethoscope On Rome post and a World Health Organization asessment), but in a Chinese bus in January 2020. The full article from early March 2020 is posted online, but for those of you who don’t understand Chinese, the handy-dandy Figure above tells you all you need to know.

Impressive study, huh? The New York Times gave it a Superspreader headline. Only one problem: 6 weeks after it was published, the bus article was quietly retracted without explanation.

The subject remains controversial. A systematic review done for the World Health Organization, prepublished in March 2021 and covering 67 studies, noted their uniformly low quality and concluded: “SARS-COV-2 RNA can be detected intermittently by RT-PCR in the air in a variety of settings. A number of studies that looked for viral RNA in air samples found none, even in settings [such as COVID-19 ICUs] where surfaces were found to be contaminated with SARS-CoV-2 RNA. The lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions to be drawn about airborne transmission.” This review was promptly and sharply criticized by equally convinced authorities whose concrete proposals – ventilation, distancing, and masking indoors – are already universally accepted.

Note that even the biggest proponents of aerosol spread think the particles only hang around for a few hours and that the vast majority of particles travel only 3-6 feet, the same physical distancing we’re already respecting.

The CDC recently endorsed airborne aerosols as an important mode of COVID-19 transmission, and its scientific briefdescribes 7 outbreaks that were new to me. Several are clearly irrelevant because they involved crowded activities without masks or physical distancing: “fitness dance” and Zumba classes in Korea, choir rehearsals in France. Others seem very likely related to droplets: at adjacent tables in a Chinese restaurant, in a high-intensity exercise class in Chicago, and in a Chinese mall.

The outbreak I found most supportive of airborne spread began with a solo singer in an Australian church. He performed in a loft 3 meters high but spread the infection to 12 worshippers below. Even in this case, though, I’m not convinced it’s necessary to invoke aerosols. Singing may be the most powerful way of producing and propelling the larger droplets considered the chief mode of transmitting COVID-19, and a soloist in a loft will be spraying them downward. 

Given how many people passionately back the aerosol hypothesis, and how many pandemic months have passed, I would think if they were right they’d be citing more than this tiny handful of examples.

 

COVID out of left field

That COVID-19 outbreak among 9 vaccinated Yankees and staff, only 2 of whom had any symptoms, has caused plenty of stir. Several people have sent me this article about it, an interview with Harvard epidemiologist Michael Mina, who has an antigen-test axe to grind. I find the interview misleading, and perhaps disingenuous since I don’t think Prof. Mina can plead ignorance. He claims:

1) A negative antigen test means that if you are infected, your viral load is so low you cannot be infectious. This is nonsense, and potentially dangerous nonsense. 

2) “It is very unlikely that these vaccines will create fully sterilizing immunity.” i.e. vaccines may allow the virus to multiply in your nose even though they keep you from getting sick. What’s wrong here is lumping “these vaccines.” The Pfizer vaccine does in fact give sterilizing immunity, preventing 94% of asymptomatic infections. The J&J vaccine does not, preventing only 74%. Guess which one the Yankees got? 

3) “The PCR test is full of false positives.” Yes, small noninfectious fragments of viral RNA can linger on in the nose following COVID-19 and cause positive PCR tests in people who are no longer contagious. But there are no false positives on PCR tests in acute cases. Since the Yankees were apparently being tested 3 times a day (!) with both PCR and antigen swabs and this was the first positive test for all but one of them, the false positive issue is irrelevant. 

Dr. Paul Sax, a reputable infectious diseases expert, thinks all the Yankee cases likely came from a single superspreader, and hints that the vaccines the team received might have come from a faulty batch. I had the same suspicion about a deadly outbreak among vaccinated residents and staff in a Kentucky nursing home.

…as long as we’re on sports, did you know that on May 28^th only 6.4% of people in Japan had had a dose of vaccine? I sure didn’t. And their epidemic, though never very intense, is not under control. 

 

They’ve hustled like mad in June, nearly catching up with India but still with only 13.9% vaccinated. Under those circumstances, it seems to me that unless they mandate vaccination, which they haven’t, going forward with the Olympics this summer is folly (83% of Japanese think so). Pfizer has offered to vaccinate staff and athletes, but even the organizers expect one in 5 to refuse. And it looks like local spectators (the only kind allowed to attend) will be able to get away with merely negative swabs from many days earlier.

 

 

Now, about those leaky labs…

The pendulum may be swinging back in the direction of a natural origin for the novel coronavirus. You might want to check out a sober and well-reasoned Washington Post op-ed by two virologists, laying out the case against the lab leak hypothesis. Call it a rebuttal to the Wade article I cited in my last post. The LA Times published another good piece, a third, in Nature, comes down on the same side of the fence …and one of the most impressive pro-lab leak voices, Nobel laureate David Baltimore, who said in May he had detected a genetic “smoking gun,” has now had second thoughts.

 

Mark Grenon, "Archbishop of the Genesis II Church of Health and Healing," with MMS

Miracle Mineral Solution redux: I wrote last August: “Did you miss the Guardian article back in April that revealed where Trump got the idea of drinking disinfectants? So did I, but we can all catch up now that the bleach peddlers – a Florida father-and-son team – have been arrested in Colombia and are awaiting extradition. Local authorities say their Miracle Mineral Solution, which ‘cures’ not only COVID-19 but cancer, AIDS, and autism, has killed at least 7 Americans.” …Well guess what – the Grenon gang is back in the news! Apparently the extradition flopped, the guys are still in Colombia, they’re still hawking bleach, and they’ve been indicted again – though only for conspiracy to commit fraud and criminal contempt, not for manslaughter. Wonder whether Colombia will keep its paws on them this time.